ACP-Supported-Research-Projects_Overview_7.10.12_v1

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1                                    ACP Supported Research Projects: Overview
2                                    Last Updated 7.10.12
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                                                          Disease or   Biological Target Primary                                        Study
6 Title                              Key Topics           Disorder     or Gene           Investigator       Location        Approved    Status         Updated      Samples    # participants            Funded By         Results                                   Description
                                                                                                                                                                                                                                                                     Questcor manufactures a drug called Acthar (native ACTH gel) which is a steroidogenic hormone but may
                                                                                                                                                                                                                                                                     also have other effects relevant to MS. Scientists at this company are interested in understanding the
    Analysis of repository data                                                                                                         MTA/DTA                                                                                                                      efficacy of relapse treatment in patients with relapsing remitting MS, beginning with basic data analysis to
7   for relapse treatment trends     Data Visualization MS                               Heidi Mace         Questcor        3/22/2011   Signed         6/7/2011     Data       N/A                       Questcor          Pending                                   understand general trends.
                                                                                                                                                                                                                                                                     Science Commons will be applying and building ontologies in order to structure patient registry data for
    Building ontologies to                                                                                                                                                                                                                                           effective query and analysis. By making primary data structured in a clear and consistent way and enabling
    structure patient registry                                                                              Science                     Product                                                                                                                      computation researchers easy access we hope to make it easier for computational scientists to apply new
8   data                             Data Visualization                                  Alan Ruttenberg    Commons         5/15/2008   Delivered      8/27/2008    Data       N/A                       -                 Pending                                   methods to mine this data.

                                                                                                                                                                                                                                                                     Data visualization experts at KVS, in partnership with Accelerated Cure Project, will produce highly
                                                                                                            Knowledge                                                                                                                                                sophisticated systemic maps based upon ACP's repository data and other sources of knowledge about MS.
    Generation of interactive                                                                               Visualization               Study in                                                                                                                     The team's goal is to provide interactive maps of the data and knowledge associated with MS and create a
9   maps using repository data       Data Visualization MS                               Alan Yelsey        Systems         3/22/2011   Progress       6/7/2011     Data       N/A                       KVS               Pending                                   unique interactive disease framework that produces new insights into MS.

                                                                                                                                                                                                                                                                     A team at UMBC will be analyzing our repository database using machine learning techniques to find
   Application of interactive                                                                                                                                                                                                                                        patterns in the data that may reveal disease subtypes or factors that may cause or be correlated with a
   classification and clustering                                                                                                                                                                                                                                     demyelinating disease. Machine learning involves programming computers so that they can automatically
   techniques to the repository                                                                             University of               Study in                                                                                                                     recognize patterns or make decisions based on input they are given. The breadth and diversity of data in
10 database                          Data Visualization                                  Marie desJardins   Maryland        1/26/2010   Progress       2/26/2010    Data       N/A                       -                 Pending                                   our database makes it a good candidate for analysis by these types of techniques.

                                                                                                                                                                                                                           Presented at the AAN 2010 Annual
                                                                                                                                                                                                                           Meeting: Antibodies (gMS[Dx Test)
                                                                                                                                                                               868 cases (743 MS, 71                       Differentiate Newly Diagnosed Relapsing
                                                                                                                                                                               TM, 13 NMO, 4 ON, 6                         Remitting Multiple Sclerosis Patients from
    The ability of anti-glucose                                                                                                                                                ADEM, 31 CIS), 140                          Other Inflammatory Demyelinating
    antibodies to diagnose and                                                                              Glycominds                                                         unrelated controls and                      Disease Patients within One Year from      Glycominds used samples from our repository to validate an assay based on anti-glucose antibodies. This
11 stratify MS patients              Diagnostics          MS                             Nir Dotan, PhD     Ltd.            7/15/2008   Completed      4/1/2009     Serum      251 related controls      Glycominds        Diagnosis                                  assay is being developed for use in diagnosing MS and predicting different aspects of the disease.

                                                                                                                                                                                                                                                                     Samples are being analyzed to confirm blood-based gene expression patterns that discriminate between
   Human gene expression for                                                                                                                                                                                                                                         MS and non-MS subjects and could form the basis for a type of diagnostic test. A test capable of providing
   developing an MS diagnostic                                                           Douglas Bigwood,                                                                      70 cases (60 MS and 10                                                                an early and definitive diagnosis of MS and differentiating MS subtypes would not only facilitate earlier
12 signature                   Diagnostics                MS                             PhD              Diogenix, Inc.    9/1/2007    Completed      6/4/2008     RNA        TM) and 50 controls       Gene Logic Inc.   Received                                  delivery of proper therapy but would help alleviate undue anxiety for patients and their families.

   Establish biomarker profiles                                                                             Pfizer                                                             50 cases (MS-RRMS)                                                                    Scientists at Pfizer are analyzing samples from our repository to gain a better understanding of disease
   for patients with Multiple                                                            Thomas Misko,      Inflammation                                            EDTA       and 50 cases (MS-                                                                     activity and progression in MS. Results from their analysis may help in the development of new therapies
13 Sclerosis                         Diagnostics          MS                             PhD                Research        9/22/2009   Completed      2/3/2010     plasma     SPMS)                     Pfizer            Received                                  as well as lead to new methods for monitoring the clinical course of MS.

                                                                                                                                                                                                                        Results of study indicated gene
                                                                                                                                                                                                                        expression signatures in blood can           Multiple sclerosis is a disease that is difficult to diagnose. Diagnosis in early stages of disease would be
                                                                                                                                                                                                                        accurately support or exclude diagnosis of   facilitated by an accurate blood test and this is key to timely institution of definitive therapies that reduce
                                                                                                                                                                                                                        MS. "Gene-expression signatures:             the rate of disease progression and onset of disability. The goal of our research is to develop an accurate
                                                                                                                                                                               111 cases (80 MS, 20                     biomarkers toward diagnosing multiple        blood test for multiple sclerosis and evaluate its performance in different subject populations. A simple in
    Creation of in vitro                                                                 Thomas M. Aune,                                                                       TM, 6 NMO, 1 ON, 4                       sclerosis." Genes and Immunity,              vitro diagnostic blood test for MS could decrease the time between the time of onset of clinical symptoms
14 diagnostic blood test for MS      Diagnostics          MS                             PhD             Vanderbilt         9/17/2008   Completed      4/1/2009     RNA        ADEM)                     NIH STTR grant September 22, 2011.                          of MS and a definitive diagnosis of MS. It could also aid in excluding someone from having MS.

                                                                                                                                                                                                                                                                     Antibodies that bind to the molecule aquaporin-4 (AQP4) are often found in the blood of people diagnosed
                                                                                                                                                                                                                                                                     with NMO. AQP4 is expressed in central nervous system cells called astrocytes, but it is expressed in other
   Use PCR based assay to look                                                                                                                                                                          Guthy-Jackson                                                cells as well. Dr. Levy's project involves measuring levels of a certain form of AQP4 in white blood cells to
   for isoforms of aquaporin-4                                                           Michael Levy, MD, Johns Hopkins                Distribution                           21 cases (5 MS, 5 TM, 11 Charitable                                                   see whether these levels change during relapse and remission. This research may lead to development of
15 (AQP4)                      Diagnostics                NMO, RRMS AQP4                 PhD               University    3/19/2010      Wrap Up        1/6/2011     RNA        NMO) and 5 controls      Foundation         Received                                  a biomarker of NMO disease activity.

                                                                                                                                                                                                                                                                     In this collaborative project, researchers from UC San Francisco and UT Southwestern will be examining
   Determine the affinity and                                                                             University of                                                                                                                                              how strongly IgG antibodies found in serum of NMO subjects bind to the different forms of aquaporin-4.
   efficacy of NMO-IgG binding                                                                            California San                                                                                 Guthy-Jackson                                               The goal of the research is to correlate binding characteristics of NMO-IgG with various parameters,
   to the M1 and M23 isoforms                                                            Alan S. Verkman, Francisco, UT                 Study in                               36 cases (24 NMO, 12      Charitable                                                  including age, sex, age of onset, years of disease, disease severity, and treatment status. The information
16 of AQP4                           Diagnostics          NMO          NMO-IgG, AQP4     MD, PhD          Southwestern      3/18/2010   Progress       1/6/2011     Serum      MS)                       Foundation                                                  from these studies may provide a novel serum diagnostic test of disease severity and response to therapy.
                                                                                                                                                                                                         Multiple
                                                                                                                                                                                                         Sclerosis                                                   Drs. Butzkueven and Gresle will be analyzing serum samples for the presence of phosphorylated
   Analyzing presence of                                                                                                                                                                                 Research                                                    neurofilament heavy chain (pNF-H), which is a possible marker of neurodegeneration in MS. Levels of pNF-
   phosphorylated                                                                        Helmut             Howard Florey               Study in                               733 cases (MS) and 100    Australia                                                   H will be correlated both with disease severity indicators and with the metabolite data that has been
17 neurofilament heavy chain         Diagnostics          MS           pNF-H             Butzkueven, MD     Institute       4/22/2010   Progress       10/20/2010   Serum      controls                  (MSRA)            Pending                                   generated by Dr. Gilles Guillemin's analysis of the same samples.
                                                                                                                                                                               83 cases (50 MS, 12                                                                   Researchers at MSDx have found that levels of a protein called visfatin are elevated in people with MS.
                                                                                                                                                                               Tysabri x2, 14 Copaxone                                                               They are using plasma samples from the Accelerated Cure Project to further explore and validate this
    Analysis of visfatin levels in                                                       Ramesh C.                                      Study in                               x2, 7 Avonex x2), 10                                                                  finding. Visfatin is associated with obesity and metabolism, but also promotes inflammation, which may
18 plasma samples                    Diagnostics          MS           visfatin          Nayak, PhD         MSDx, LLC       2/8/2010    Progress       1/6/2011     Plasma     controls                  MSDx              Pending                                   form the basis of its potential connection with MS.
                                                                                                                                                                                                                                                                     Researchers at the Partners MS Center have been working to find biomarkers that can diagnose MS,
                                                                                                            Brigham &                                                          193 cases (147 MS, 24                                                                 predict clinical course, and gauge risk of MS. Samples from the Accelerated Cure Project repository will be
    Analysis of immune-related                                                           Philip DeJager,    Women's                     Study in                               TM, 22 CIS) and 100                                                                   used to validate a set of 22 biomarkers involved in inflammation that could aid in establishing a diagnosis of
19 biomarkers                        Diagnostics          MS                             MD, PhD            Hospital        9/16/2009   Progress       1/6/2011     Serum      controls                  -                 Pending                                   MS.

                                                                                                                                                                                                                                                                     This is an extension of the study "Human gene expression for developing an MS diagnostic signature":
                                                                                                                                                                                                                                                                     Samples are being analyzed to confirm blood-based gene expression patterns that discriminate between
                                                                                                                                                                                                                                                                     MS and non-MS subjects and could form the basis for a type of diagnostic test. A test capable of providing
   Development of an FDA-                                                                Douglas Bigwood,                               Study in                                                                                                                     an early and definitive diagnosis of MS and differentiating MS subtypes would not only facilitate earlier
20 approved MS diagnostic test       Diagnostics          MS                             PhD              Diogenix, Inc.    1/6/2009    Progress       6/25/2009    PaxGene    pending                   Diogenix          Pending                                   delivery of proper therapy but would help alleviate undue anxiety for patients and their families.
   The ability of anti-glucose
   antibodies to monitor MS                                                                                                                                                                                                                                          The Glycominds team has developed an MS diagnostic assay based on anti-glucose antibodies. They are
   disease activity and                                                                                     Glycominds                  Study in                               271 cases (MS, 2                                                                      now interested in learning whether this assay could potentially also be used to monitor disease activity and
21 treatment efficacy                Diagnostics          MS                             Nir Dotan, PhD     Ltd.            5/20/2011   Progress       6/7/2011     Serum      timepoints each)          Glycominds        Pending                                   severity, as well as whether changes in antibody levels reflect treatment efficacy.

                                                                                                                                                                                                                                                                     MSDx is a start-up company that is developing a new technique for diagnosing and monitoring MS. This
                                                                                                                                                                                                                                                                     technique analyzes the contents of blood cells called phagocytes for evidence of brain tissue debris. MSDx
                                                                                                                                                                               110 cases (75 MS, 15                                                                  plans to develop this technique so that it can be used to help diagnose MS, monitor disease activity to
    Development of a diagnostic                                                          Ramesh C.                                      Study in                               CIS, 10 NMO, 10 ADEM) Company MSDx,                                                   prevent relapse, and monitor drug effects to distinguish responders and non-responders. Our blood
22 product for MS                    Diagnostics          MS                             Nayak, PhD         MSDx, LLC       9/1/2009    Progress       2/3/2010     PBMCs      and 10 controls       LLC           Pending                                           samples will be used to further refine this technique.
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                                                                                                                                                                      10 cases (1st phase of 3
                                                                                                                                                                      phase study) 20 cases                                                                       During our lifespan, everyone produces antibodies directed against human antigens (proteins). Usually,
                                                                                                                                                                      (MS) and 20 controls                                                                        these so-called autoantibodies do not cause disease. However, in so-called autoimmune diseases the
                                                                                                                                                                      (2nd phase of 3 phase                                                                       autoantibodies cause clinical symptoms, i.e., a disease. Protagen is developing a test to diagnose MS
   Development of a test for in-                    CIS, RRMS,                   Stefan Mullner,                                    Study in                          study) 15 controls (2a                                                                      based on the patterns of autoantibodies found in serum samples. Ideally this test will also distinguish
23 vitro diagnosis of MS           Diagnostics      SPMS                         PhD                 Protagen AG       5/20/2009    Progress    1/6/2011    Serum     phase of 3 phase study)    Protagen AG         Pending                                      among the clinical subtypes CIS, RRMS and SPMS.

                                                                                                                                                                                                                                                                  The company SomaLogic has developed a novel technology platform for finding protein biomarkers in
   Identify biomarkers that can                                                                                                                                       100 cases (50 MS, 3                                                                         plasma and serum samples. Samples from our repository will be analyzed with this platform to identify
   diagnose MS and distinguish                                                   Sally K. Nelson,                                   Study in                          NMO, 4 ON, 38 TM, 5                                                                         biomarkers that can diagnose MS and distinguish its different forms, measure a person's response to
24 its forms                       Diagnostics      MS                           PhD                 SomaLogic         11/24/2009   Progress    1/6/2011    Serum     ADEM) and 50 controls      SomaLogic, Inc. Pending                                          treatment, and provide insight into progression and severity of the disease.
                                                                                                                                                                                                 Multiple
                                                                                                                                                                                                 Sclerosis
                                                                                                                                    Data                                                         Research                                                         Researchers at St. Vincent's propose to demonstrate that tryptophan metabolism plays an important role in
   The role of tryptophan                                                        Gilles J.                                          Analysis                          733 cases (MS) and 100     Australia                                                        multiple sclerosis (MS). This project may open a new and important therapeutic door for MS using different
25 metabolism in MS                Disease Properties MS                         Guillemin, PhD      St. Vincent's     6/20/2008    Completed   4/1/2009    Serum     controls                   (MSRA)              Received                                     specific inhibitors already available from drug companies for other brain diseases.




                                                                                                                                                                                                                     Results to date:
                                                                                                                                                                                                                     - Genetic analysis of aquaporin-4 in
                                                                                                                                                                                                                     neuromyelitis optica. Neurology.
                                                                                                                                                                                                                     September 20, 2011.
                                                                                                                                                                                                                     - HLA DRB1*1501 tagging rs3135388
                                                                                                                                                                                                                     polymorphism is not associated with
                                                                                                                                                                                                                     neuromyelitis optica. Multiple Sclerosis,
                                                                                                                                                                                                                     June 30 2010 (Epub).
                                                                                                                                                                                                                     - Presentation at AAN 04/09: "The MS-
                                                                                                                                                                                                                     associated gene HLA DRB1*1501 was not
                                                                                                                                                                                                                     found to be a risk factor for NMO"
                                                                                                                                                                                                                     - Presentation at AAN 2009: "Two
                                                                                                                                                                                                                     Different Arg19 Mutations in the N-
                                                                                                                                                                                                                     terminus of Aquaporin-4 Suggest a
                                                                                                                                                                                                                     Molecular Mechanism for Susceptibility to
                                                                                                                                                                                                                     Neuromyelitis Optica"
                                                                                                                                                                                                 Multiple            - Presentation at ECTRIMS 2009:              Researchers at Mayo Clinic have discovered that a large number of patients with neuromyelitis optica, also
                                                                                                                                                                                                 Sclerosis           "Genetic analysis of neuromyelitis optica:   known as optico-spinal MS, have antibodies in the blood against a protein in the nervous system called
                                                                                                                                                                                                 International       two different Arg19 mutations in the N-      aquaporin-4. The Mayo clinic researchers are studying the gene that produces this protein. They will use
   Genetic and immunogenic                                                                                                                                                                       Federation,         terminus of aquaporin-4 suggest a            repository samples to find out whether and how mutations in this gene are linked with development of the
   analysis of AQP4 in                                                           Brian                                                                                                           Mayo                molecular mechanism for susceptibility to    disease, which could determine prevention initiatives. Other genetic variants will also be examined for
26 neuromyelitis optica            Genetics         NMO          AQP-4           Weinshenker, MD Mayo Clinic           11/9/2007    Completed   4/1/2009    DNA       5 cases (NMO)              Foundation          NMO"                                         involvement in NMO.



                                                                                                                                                                                                                   Results from study implicate genetic and       Researchers at UCI have found that genetic deficiency in a pathway that controls the addition of specific
                                                                                                                                                                                                                   environmental factors that affect protein      sugars to proteins leads to immune hyperactivity and spontaneous development of an MS-like disease in
                                                                                                                                                                      871 cases (746 MS, 13                        glycosylation as playing a role in MS.         mice. They have identified two genetic defects in humans that alter the same glycosylation pathway.
                                                                                                                                                                      NMO, 4 ON, 69 TM, 8                          - Genetics and the environment converge        Repository samples will be used in conjunction with other samples to identify additional genetic changes
   Gene alleles that affect                                      Glycosylation   Michael             University of                                                    ADEM, 31 CIS) and 18       National Multiple to dysregulate N-glycosylation in multiple     that lead to the same defect in protein glycosylation and show that these can also be treated by metabolic
27 protein glycosylation           Genetics         MS           pathway         Demetriou, MD       California Irvine 4/4/2008     Completed   6/7/2011    DNA       unrelated controls         Sclerosis Society sclerosis. Nat Commun . 2011.                  therapy.

                                                                                                                                                                                                                     No significant differences found in
                                                                                                                                                                                                                     frequencies of Prnp129 genotypes in
                                                                                                                                                                                                 Partly covered by   PPMS subjects compared with controls.
                                                                                                                                                                                                 a Merit Review      - No association between genetic             Around 10% of people with MS have the primary progressive form of the disease, which can have a severe
                                                                                                                                                                                                 Grant to Dr.        polymorphism at codon 129 of the prion       course and is not affected by any of the current MS disease-modifying therapies. Mutations in a gene
                                                                                                     University of                                                                               Stuve by the        protein gene and primary progressive         called PrP (prion protein) have been found to increase the severity of other neurological diseases such as
   Determine role of prion                                                       Olaf Stuve, MD,     Texas                                                                                       Department of       multiple sclerosis. Arch Neurol. February    Alzheimer's disease. A team at UTSW will analyze samples from subjects with PPMS for the presence of a
28 protein in patients with PPMS Genetics           MS           PrP             PhD                 Southwestern      10/20/2010   Completed   5/17/2011   DNA       69 cases (MS)              Veterans Affairs.   2011.                                        PrP mutation that has been associated with severity in another neurodegenerative disease.
                                                                                                                                                                                                 Guthy-Jackson                                                    Scientists at 23andMe will be screening NMO samples from the repository using a GWAS (genome wide
   Whole-genome screening of                                                                                                                                                                     Charitable                                                       association study) approach. The data generated may help to identify genetic variants that are more
29 NMO samples                     Genetics         NMO                          Joyce Tung          23andMe           3/22/2011    Completed   6/7/2011    DNA       115 cases (NMO)            Foundation          Pending                                      common in people who have NMO than in people who do not.

                                                                                                                                                                                                                                                                  Samples will be used to explore the role of Vitamin D as it relates to MS. Researchers will be considering
                                                                                                                                                                                                                                                                  genes involved in Vitamin D metabolism and investigating how these might be related to an individual's risk
   Investigating the involvement                                                                     Harvard School                                                                                                                                               of MS. By considering potential genetic factors, researchers may be able to determine if certain individuals
   of Vitamin D related genes                                                    Alberto Ascherio,   of Public                                                        650 cases (MS) and 243     NIH (Grant:                                                      would benefit even more from increased Vitamin D and potentially further elucidate what the underlying
30 and MS                        Genetics           MS                           MD, PhD             Health         3/10/2008       Completed   6/7/2011    DNA       controls                   R01)                Received                                     biological effect of Vitamin D may be as it relates to MS.


                                                                                                                                                                                                                     Several genetic associations discovered or
                                                                                                                                                                                                                     confirmed.
                                                                                                                                                                                                                     - Genetic variation in the IL7RA/IL7
                                                                                                                                                                                                                     pathway increases multiple sclerosis
                                                                                                                                                                                                                     susceptibility. Human Genetics. January
                                                                                                                                                                                                                     30 2010 (Epub)
                                                                                                                                                                                                                     - Meta-analysis of genome scans and
                                                                                                                                                                                                                     replication identify CD6, IRF8 and
                                                                                                                                                                                                                     TNFRSF1A as new multiple sclerosis
                                                                                                                                                                                                                     susceptibility loci. Nature Genetics. July
                                                                                                                                                                                                                     2009.
                                                                                                                                                                                                                     - IL12A, MPHOSPH9/CDK2AP1 and
                                                                                                                                                                                                                     RGS1 are novel multiple sclerosis
                                                                                                                                                                                                                     susceptibility loci. Genes and Immunity.
                                                                                                                                                                                                                     June 17 2010 (Epub).
                                                                                                                                                                                                                     - Comprehensive follow-up of the first       Repository samples were used to validate the results of a previous genome scan conducted on 1000 MS
                                                                                                                                                                      735 cases (640 MS, 11                          genome-wide association study of multiple    subjects. The scan was done to discover genetic variants that affect the course of disease in patients with
   Validation of genetic                                                                                                                                              NMO, 3 ON, 54 TM, 4                            sclerosis identifies KIF21B and TMEM39A      MS. The genetic variants may help explain why MS progresses differently in its patients. Samples are also
   determinants of disease                                                       Philip DeJager,                                                                      ADEM, 23 CIS) and 242      Accelerated         as susceptibility loci. Human Molecular      being used in projects performed by the International MS Genetics Consortium to explore and confirm
31 course in MS                    Genetics         MS                           MD, PhD             Broad Institute   2/22/2008    Completed   6/25/2009   DNA       controls                   Cure Project        Genetics . December 23 2009 (Epub).          genetic associations with MS.
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                                                                                                                                                                                                                       This genome-wide association study
                                                                                                                                                                                                                       replicated almost all previously suggested
                                                                                                                                                                                                                       associations and identified at least a
                                                                                                                                                                                                                       further 29 novel loci associated with MS
                                                                                                                                                                                                                       susceptibility. Genes involved in immune
                                                                                                                                                                                                                       system figured significantly in list of
                                                                                                                                                                                                                       results. Further progress made on
                                                                                                                                                                                                                       understanding the contribution of HLA-
   An international                                                                                                                                                                                                    DRB1 to MS risk.                              The Wellcome Trust is funding an international collaboration to perform whole-genome screens on several
   collaboration to perform                                                                                                                                                                                            - Genetic risk and a primary role for cell-   thousand MS samples. Accelerated Cure Project has contributed DNA samples to this effort, which aims to
   whole-genome screens on                                                        Philip DeJager,     Wellcome                                                                                                         mediated immune mechanisms in multiple        screen MS samples for genes that affect the risk of MS. The whole-genome screens could allow a better
32 MS samples                        Genetics       MS                            MD, PhD             Trust Project    5/22/2008    Completed     6/7/2011     DNA         574 cases (MS)          Wellcome Trust      sclerosis. Nature. August 11, 2011.           understanding of the causes of MS.




                                                                                                                                                                                                                       Two sets of results from study published
                                                                                                                                                                                                                       identifying gene variants that appear to
                                                                                                                                                                                                                       affect MS risk and severity.
                                                                                                                                                                                                   National Multiple   - Association of common mitochondrial
                                                                                                                                                                                                   Sclerosis Society   DNA variants with multiple sclerosis and
                                                                                                                                                                                                   (Grants:            systemic lupus erythematosus. Clinical
                                                                                                                                                                                                   RG3521A6/T          Immunolology. October 2008.                   Researchers at the Syracuse VA Medical Center used our samples to explore gene variations in MS
                                                                                                      SUNY Upstate                                                                                 and NMSS            - CCL genes in multiple sclerosis and         subjects and unaffected healthy individuals to determine how variations in inflammatory genes contribute to
   Variations in inflammatory                                                     Bernadette          Medical                                                                                      PP1334),            systemic lupus erythematosus. Journal of      the development of MS. They also studied whether these genetic variations correlate with disease severity.
33 genes                             Genetics       MS                            Kalman, MD          University    12/1/2006       Completed     5/27/2008    DNA         150 cases (MS)          Serono Inc.         Neuroimmunology. August 30 2008.              Specific gene variants could explain why some MS patients develop more severe symptoms than others.
   Association of CD24 gene                                                                           University of                 Study in                                                                                                                         Dr. Liu and his colleagues are validating previous results in mouse models and human samples suggesting
34 variants with MS                  Genetics       MS         CD24               Yang Liu, MD        Michigan      1/21/2011       Progress      6/7/2011     DNA         500 cases (MS)           -                  Pending                                       that variants in the CD24 gene may affect the risk of MS.

                                                                                                                                                                                                                                                                     A regulatory protein called SHP-1 can control the inflammatory activities of immune cells. People with MS
                                                                                                                                                                                                                                                                     have been found to be deficient in SHP-1 compared with controls, and this deficiency has been shown to
   Determining information on                                                                     SUNY Upstate                                                                                                                                                       contribute to the increased expression of pro-inflammatory genes. This research study will explore whether
   DNA methylation in the SHP-1                                                                   Medical                           Study in                               50 cases (MS) and 200                                                                     a certain type of modification (called methylation) to the SHP-1 gene is responsible for decreased SHP-1
35 gene                         Genetics            MS         SHP-1              Paul Massa, PhD University   7/24/2009            Progress      12/16/2009   DNA         controls                NIH                 Pending                                       levels in people with MS. We are providing DNA samples to support this study.

   Whole blood gene expression                                                                                                                                                                                                                                       The goal of this research proposal is to investigate the whole blood gene expression profiles of MS patients
   profiling of samples from                                                                                                                                                                                                                                         and specifically Secondary Progressive MS (SPMS) patients to better understand the molecular features of
   secondary progressive MS                         SPMS,                         Jadwiga                                           Study in                               214 cases (MS) and 30                                                                     SPMS versus Relapsing-Remitting MS (RRMS). We believe that a better understanding of the involvement
36 subjects                    Genetics             RRMS                          Bienkowska          Biogen Idec      1/21/2011    Progress      6/7/2011     PaxGene     controls                Biogen IDEC         Pending                                       of the immune system in SPMS could lead to new therapies and improve lives of MS patients.

                                                                                                                                                                                                                                                                     The production of proteins in cells is affected by many factors, one of which is the presence of a type of
                                                                                                                                                                           225 cases (MS, NMO,                                                                       molecule called micro RNA (miRNA). miRNAs are small RNA molecules that affect the stability and
   Find gene expression                                                           Eric M. Eastman,                                  Study in                               TM, ADEM, ON) and 114                                                                     translation of messenger RNA (mRNA) molecules. Diogenix is including miRNA analysis in their ongoing
37 patterns by analyzing miRNA Genetics             MS                            PhD                 Diogenix, Inc.   11/20/2009   Progress      1/6/2011     Serum       controls              Diogenix              Pending                                       efforts to find gene expression patterns that can diagnose and classify MS.

                                                                                                                                                                                                                                                                     Some studies indicate that familial MS may take a more severe course than non-familial MS, and therefore
   Investigation of familial MS                                                                                                                                                                                                                                      different mechanisms may underlie familial MS and sporadic MS. Dr. Han's team plans to sequence the
   through genome sequencing                                                                                                                                                                                                                                         genome in familial MS and also screen samples on the functional level by using protein arrays. By
   and functional protein                                                                                                           Study in                   DNA and     14 cases (MS and TM)                                                                      comparing both genomic data and protein array data, they hope to find potential genetic markers and/or
38 screening                         Genetics       MS                            May Han, MD         Stanford         5/20/2011    Progress      6/7/2011     serum       and 7 controls          Internal funding    Pending                                       promising pathogenic proteins playing roles in familial MS.


                                                                                                                                                                                                                                                                     A research team from Oklahoma Medical Research Foundation (OMRF) used samples collected during
                                                                                                                                                                                                                       Poster/findings presented at Federation       the pilot phase of the repository to study the relationship between the Epstein-Barr virus (EBV) and MS.
                                                                                                                                                                                                                       of Clinical Immunology Societies (FOCIS)      Building upon their prior work studying EBV and systemic lupus erythematosus (SLE), the researchers
                                                                                                                                                                                                                       annual meeting in June 2006. Based on         focused on studying the response of MS subjects to EBV, based on the hypothesis that the immune
                                                                                                                                                                                                                       the samples from MS subjects and              system response of MS patients to EBV differs from that of non-affected individuals, while their responses
                                                                                                      Oklahoma                                                                                     Oklahoma            unaffected controls studied, it was           to other common viruses (chickenpox, herpes simplex 1 and 2, etc.) are quite similar. Based on the
    Humoral response of MS                                                                            Medical                                                                                      Medical             reported that MS subjects did appear to       samples from MS subjects and unaffected controls that they studied, they reported that MS subjects did
    patients to the Epstein-Barr                               Epstein-Barr virus, Judith A. James,   Research                                                             15 cases (MS) and 7     Research            have a unique response to the major           appear to have a unique response to the major nuclear antigen of EBV, EBNA-1. With further research,
39 virus                             Immunology     MS         EBV, EBNA-1         MD, PhD            Foundation       9/26/2005    Completed     12/29/2007   Serum       controls                Foundation          nuclear antigen of EBV, EBNA-1                this unique response could reveal EBV as a possible cause of MS.

                                                                                                                                                                                                                                                                     Repository samples will be used in the largest screen for active pathogens (viruses, bacteria, and fungi)
   Identification of a host-                                                                                                                                                                                                                                         ever undertaken in subjects with MS. Additionally, the human gene expression levels of these subjects will
   pathogen interaction in                                                                                                                                     DNA and     20 cases (MS) and 20                                                                      be analyzed in order to identify a pattern of host-pathogen interactions that are present in people with MS.
40 people with MS                    Immunology     MS                            Viktor Stolc, PhD   NASA             3/22/2007    Completed     4/1/2009     RNA         controls                NASA                Pending                                       If a pattern is found, it could explain how MS is caused.
                                                                                                                                                                                                                                                                     Researchers at the Stanford School of Medicine are using samples collected during the pilot phase of the
                                                                                                                                                                                                                                                                     repository to assess the presence of antibodies that target the blood-brain barrier (BBB). Their research is
                                                                                                                                    Data                                                                                                                             focused on the role of the BBB in the progression of MS and whether the BBB is the target of an immune
   Antibodies to blood-brain                                                       Ben Barres, MD,                                  Analysis in                            25 cases (MS) and 13    Myelin Repair                                                     response which may lead to MS. If the BBB plays a significant role in MS, it may enable better treatments
41 barrier                           Immunology     MS         Blood brain barrier PhD                Stanford         7/5/2006     Progress      10/16/2007   Serum       controls                Foundation          Pending                                       and possible cures to be discovered.
   Molecular Studies of                                                                                                                                                                                                                                              Researchers at The Scripps Research Institute are developing a mouse model of autoimmunity to AQP4,
   Neuromyelitis Optica in                                                                            The Scripps                                                                                  Guthy-Jackson                                                     which can be used to better understand the human disease neuromyelitis optica (NMO) and develop novel
   Mouse Models of Aquaporin-                                                     Roberto Baccala,    Research                      Study in                               5 cases (NMO) and 5     Charitable                                                        therapies for it. Serum samples from subjects with NMO and controls will be used to develop and validate
42 4 Autoimmunity                    Immunology     NMO        AQP4               PhD                 Institute        5/20/2009    Progress      6/25/2009    Serum       controls                Foundation          Pending                                       this mouse model.

                                                                                                                                                                                                                                                                     An antibody to a protein called aquaporin-4 (AQP4) has been found in a majority of people with
                                                                                                                                                                                                                                                                     neuromyelitis optica (NMO). Discovery of this antibody, NMO-IgG, has improved the diagnosis of NMO,
                                                                                                                                                                                                                                                                     provided new insights into how the disease develops, and suggested new therapeutic strategies. A
                                                                                                                                                                                                                                                                     research team at UCSF will investigate several key aspects of the roles of AQP4 and NMO-IgG at the
    Determining whether NMO-                                                                   University of                                                                                       Guthy-Jackson                                                     molecular level and the astrocyte cell level. They will determine whether the antibody to AQP4 affects
    IgG affects important                                                     Alan S. Verkman, California San                       Study in                               10 cases (NMO) and 5    Charitable                                                        important functions of AQP4 in cells, such as allowing water through cell membranes, assembling into
43 functions of AQP4                 Immunology     NMO        AQP-4, NMO-IgG MD, PhD          Francisco               3/17/2009    Progress      4/22/2009    Serum       controls                Foundation          Pending                                       structured arrays, and facilitating cell movement.

                                                                                                                                                                                                                                                                     Dr. Waldman and his team have discovered the presence of autoantibodies that bind to endothelial cells
                                                                                                                                                                                                                                                                     (the cells that line the inner surface of blood vessels) in the blood of patients with several diseases,
                                                                                                                                                                           36 cases (10 RRMS 2                                                                       including Susac's syndrome (SS). Their experiences with SS have led them to hypothesize that endothelial-
    Detection of autoantibodies                                                                                                                                            timepoints each, 10                                                                       reactive autoantibodies may also contribute to the disease process in MS, as well as other disorders such
    that bind to endothelial cells                                                                                                                                         SPMS, 4 ADEM, 4 NMO,                                                                      as TM, NMO, ADEM and ON, possibly by disruption of the blood-brain barrier. They plan to apply their
    in serum from people with                       TM, NMO,                       W. James           The Ohio State                Study in                               4 ON, 4 TM) and 10                                                                        sensitive antibody-detection methods to serum samples from our repository to determine whether these
44 demyelinating diseases            Immunology     ADEM, ON   Blood brain barrier Waldman, PhD       University     7/21/2011      Progress      9/29/2011    Serum       controls             NIH/NINDS              Pending                                       antibodies are indeed present.
                                                                                                                                                                           80 cases (MS) and 80
                                                                                                                                                                           controls (EBV study), 854
                                                                                                                                                                           cases (654 MS, 78 NMO,
                                                                                                                                                                           122 TM) and 215 controls
                                                                                                                                                                           (DNA), 1550 cases (1238                                                                   Epstein-Barr virus (EBV) and infectious mononucleosis have both been associated with MS in numerous
                                                                                                                                                                           MS, 100 NMO, 11 ON,                                                                       studies, but the mechanism by which EBV affects MS risk is not yet understood. Dr. Ascherio and his team
   Exploration of EBV immune                                                                          Harvard School                                                       133 TM, 22 ADEM, 46                                                                       are analyzing repository samples and data from a number of standpoints to further explore the EBV/MS
   response and interactions                                                      Alberto Ascherio,   of Public                     Study in                   DNA, serum, CIS) and 464 controls                                                                     connection. For instance, they are determining whether genetic and environmental factors associated with
45 with other MS risk factors        Immunology     MS         Epstein-Barr virus MD, PhD             Health         5/6/2010       Progress      6/7/2011     whole blood (serum)                   ACP               Pending                                       MS risk correlate with antibody levels to EBV.
                 A                        B              C           D               E                 F              G           H            I            J                K                     L                     M                                                         N                                                          O
   Testing MS and control                                                                                                                                                                                                    Drs. Warmoth and Collins are testing a hypothesis that the infectious organism Mycobacterium avium
   samples for exposure to                                   Mycobacterium   Michael Warmoth, Spectrum                       Study in                            30 cases (MS) and 20                                        could be a trigger of MS. In this pilot study, they will test serum samples from MS and control subjects for
46 Mycobacterium avium            Immunology      MS         avium           MD               Health            12/3/2010    Progress    5/17/2011   Serum       controls                  Internal funding   Pending        evidence of infection with this bacteria.
   Testing the hypothesis that
   unnatural amino acid                                                                                                                                                                                                      Dr. Butte is conducting a pilot study to test the hypothesis that the incorrect incorporation of an amino acid
   misincorporated into myelin                                                                                                                                                             CTSA-sponsored                    found in certain foods into myelin basic protein (MBP) changes the structure of MBP, making it subject to
   basic protein makes it                                    Myelin basic    Manish J. Butte,                                Study in                                                      project called                    immune attack. The experiment will test how T cells from the blood of people with MS will react when
47 immunogenic                    Immunology      MS         protein         MD, PhD            Stanford        5/18/2010    Progress    1/6/2011    Whole blood 11 cases (MS), 8 controls SPAR           Pending            exposed to this altered form of MBP.

   Development of a PML risk                                                                                                                                                                                                 Dr. Calabresi is collaborating with Dr. Susan Goelz at Biogen Idec to test for JC virus antibodies in banked
   prediction method using JCV                                               Peter Calabresi,   Johns Hopkins                Study in                                                                                        sera from MS patients who have been treated with natalizumab and subsequently developed PML. This
48 antibodies                     Immunology      MS                         MD                 University    1/21/2011      Progress    6/7/2011    Serum       1 case (MS) to date       Biogen IDEC        Pending        effort will contribute to methods for predicting risk of developing PML.

                                                                                                                                                                                                                             This study will analyze the ACP database to determine if early life exposure to siblings impacts the risk of
                                                                                                                                                                                                                             developing MS. Some studies have found a correlation between early life exposure to infants and
                                                                                                                                                                                                                             decreased risk of MS which may relate to the hygiene hypothesis of autoimmune diseases. According to
   Determine if early life                                                   Benjamin M.        University of                                                                                                                the theory, having exposures to viral infections during development reduces the risk of an autoimmune
   exposure to siblings impacts                                              Greenberg, MD,     Texas                        Study in                                                                                        condition such as MS. Determining if this is true in a large scale survey could significantly impact our
49 the risk of MS               Immunology        MS                         MHS                Southwestern    10/7/2009    Progress    2/3/2010    Data        N/A                       -                  Pending        understanding of the triggers for these diseases.

                                                                                                                                                                                                                             Immune cells called neutrophils have been identified in NMO lesions but are scarce in lesions of other
                                                                             Marios             St. George's,                                                                              Guthy-Jackson                     demyelinating diseases such as MS and ADEM. These infiltrating neutrophils secrete elastase, which
   Measurement of neutrophil                                                 Papadopoulos,      University of                Study in                            55 cases (20 MS and 35    Charitable                        damages the brain. This study aims to evaluate whether neutrophil elastase concentration and activity are
50 elastase in NMO samples        Immunology      NMO                        MD FRCS(SN)        London          1/21/2011    Progress    6/7/2011    Plasma      NMO)                      Foundation         Received       elevated in NMO patients during an acute attack, but not in NMO patients in remission or in MS patients.

                                                                                                                                                                                                                             Recent studies of brain tissue have demonstrated that the brains of people with secondary progressive MS
                                                                                                                                                                                                                             (SPMS) may feature subtle but diffuse inflammation. Other experiments analyzing brains of patients with
                                                                                                                                                                                                                             SPMS have shown signs of decreased oxygen, otherwise termed "hypoxic" injury. Dr. Birnbaum and his
                                                                                                                                                                                                                             team will investigate serum samples from people with MS and controls to see whether antibodies
   Neurodegeneration in people                                               Julius Birnbaum,   Johns Hopkins                                                    619 (MS) and all available                                  associated with hypoxic injury are present, along with typical risk factors of blood vessel injury, to explore
51 with SPMS                      Risk Factors    SPMS                       MD, MHS            University    12/31/2008     Completed   4/22/2009   Serum       controls                   NIH K12 grant     Pending        the possibility that injury to blood vessels may trigger neurodegeneration in people with SPMS.



                                                                                                                                                                                                                             Mutations in mitochondrial DNA (mtDNA) have been associated with severe optic nerve injury in patients
                                                                                                                                                                                                                             with a disorder known as Leber's Hereditary Optic Neuropathy (LHON), and the same mutations also have
                                                                                                                                                                                                                             been identified in very rare MS patients, usually in association with severe optic nerve involvement.
                                                                                                                                                                                                                             Numerous prior studies have examined the possibility that LHON-associated mtDNA mutations or other
                                                                                                                                                                 382 cases (346 MS, 6      Canadian                          mtDNA variants might influence the risk of MS or clinical features of MS, but a definitive answer is lacking.
                                                                                                Beth Israel                                                      NMO, 2 ON, 19 TM, 1       Pediatric                         As a result, researchers at Beth Israel Deaconess Medical Center are using samples to examine mtDNA
   Variations in mitochondrial                                               David K. Simon,    Deaconess                                                        ADEM, 8 CIS) and 31       Demyelinating                     variants hypothesized to play a role in the risk of MS. The results could help identify people who are at
52 DNA                            Risk Factors    LHON                       MD, PhD            Medical Center 7/25/2007     Completed   6/7/2011    DNA         controls                  Disease Initiative Received       higher risk for MS and could also help advance our understanding of the causes and treatment of MS.
   Regression analysis of                                                                                                                                                                                                    This research project analyzed data from our repository database concerning different genetic and
   genetic and environmental                                                                    St. John's                                                                                 St. John's                        environmental factors from MS and non-MS subjects, and explored what this information could reveal
53 MS risk factors                Risk Factors    MS                         Xuyang Tang        University      7/8/2008     Completed   7/15/2008   Data        Not Applicable            University         Received       about risk factors for MS.

                                                                                                                                                                                                                             Whether physical trauma plays a role in causing MS has been debated since the earliest descriptions of
                                                                                                                                                                                                                             the illness, and the role of trauma in the development of MS has been the subject of many studies over the
   Exploration of trauma as an                                                                                                                                                                                               last 50 years. Investigators from Athabasca University propose to analyze our repository database and
   environmental factor that                                                 Carole Lunny,      Athabasca                    Study in                                                                                        include this information in a meta-analysis currently underway to further contribute to answering the
54 might trigger onset of MS      Risk Factors    MS                         MHS                University      7/22/2010    Progress    1/6/2011    Data        N/A                       Internal funding   Pending        question of whether trauma is associated with onset of MS.
                                                                                                                                                                                                                             Researchers at Montreal Neurological Institute (MNI) are using samples collected during the pilot phase of
                                                                                              Montreal                                                                                                                       the repository to investigate a number of possible myelin damage markers that may be detectable in the
   Investigation of myelin        Treatments/Thera                           David R. Colman, Neurological                                                       28 cases (MS) and 15      Myelin Repair                     serum of MS subjects. More knowledge of myelin damage markers could lead to more effective
55 damage markers                 peutic Targets   MS                        PhD              Institute         4/18/2006    On Hold     5/22/2006   Serum       controls                  Foundation         Pending        treatments.

                                                                                                                                                                                                                             Antibodies to the protein aquaporin-4 are commonly found in people diagnosed with NMO, and are thought
   High-throughput screening                                                                    The Scripps                                                                                Guthy-Jackson                     to cause or contribute to the disease. This study will use a high-throughput screening system to identify
   study to identify peptoid      Treatments/Thera                          Roberto Baccala,    Research                     Study in                            91 cases (10 MS, 81       Charitable                        molecules that can bind to or block anti-AQP4 autoantibodies. The results of this research could help with
56 ligands to anti-AQP4           peutic Targets   NMO       AQP-4, NMO-IgG PhD                 Institute       5/18/2010    Progress    1/6/2011    Serum       NMO) and 20 controls      Foundation         Pending        diagnosis, development of animal models, and, more importantly, the treatment of NMO.
                                                                                                                                                                                                                             GeNeuro SA is a Swiss startup company developing an innovative disease modifying therapy for the cure
                                                                                                                                                                                                                             of Multiple Sclerosis (MS). To this end, the company has generated a monoclonal antibody targeting the
                                                                                                                                                                                                                             Multiple Sclerosis Related Retrovirus (MSRV) which GeNeuro considers to be a central factor of the
   Measurement of Intracellular                                                                                                                                                                                              disease. GeNeuro will use samples from the ACP Repository to validate previous data on the frequency of
   mRNA levels of MSRV            Treatments/Thera                           Francois Curtin,                                Study in                            10 cases (MS), 10                                           MSRV and to investigate its presence in people with different forms of MS and in different geographic
57 envelope protein in PBMCs      peutic Targets   MS        MSRV            MD                 GeNeuro SA      10/19/2010   Progress    1/6/2011    PBMCs       controls                  Internal funding   Pending        locations.
                                                                                                                                                                                                                             NMO-IgG is an antibody against aquaporin-4 that has been found in the serum of people with
   Characterization of the                                                                                                                                                                                                   neuromyelitis optica (NMO). It is thought to contribute directly to the disease but how and why it is
   pathogenic NMO-IgG and the                                                                                                                                    RNA, serum, PBMCs, 40 Guthy-Jackson                         produced by B cells is unknown. Dr. Han's team will use DNA, RNA, serum, and cell samples to explore
   B cell populations producing Treatments/Thera                                                                             Study in                            cases (30 NMO and 10  Charitable                            this question. Results of this research could potentially help lead to treatments that target these antibodies
58 NMO-IgG                      peutic Targets   NMO         NMO-IgG         May Han, MD        Stanford        11/23/2010   Progress    5/17/2011   DNA         MS)                   Foundation             Pending        and/or B cells.

   Effect of treatment                                                       Benjamin M.        University of                                                                                                                A team from UT Southwestern is conducting research to analyze the impact of therapeutic intervention in
   intervention in TM and NMO     Treatments/Thera                           Greenberg, MD,     Texas                        Study in                                                                                        TM and NMO patients. In particular, they would like to learn whether timely treatment administration could
59 on disease outcome             peutic Targets   TM, NMO                   MHS                Southwestern    5/18/2010    Progress    6/4/2010    Data        N/A                       -                  Pending        help prevent disability. They will be analyzing data from our repository as part of their investigation.

				
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