Developing Treatments for Ataxia

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Developing Treatments for Ataxia Powered By Docstoc
					Barriers to Treatment
    Chip Wilmot, MD PhD
      Emory University
             Disclosure
• Member, Data Safety Monitoring Board
  for studies involving Idebenone
  (Santhera Pharmaceuticals)
 “Why Don’t We Have A
Treatment for Ataxia Yet?”
 -anonymous at NAF AMM 2012
 “Why Don’t We Have A
Treatment for Ataxia Yet?”
 -anonymous at NAF AMM 2012
     and FAPG and GAASG
      and my clinic and …
 “Why Don’t We Have A
Treatment for Ataxia Yet?”
    -Chip Wilmot, MD, PhD
       Emory University
Treatment

the care and management of a
patient to combat, ameliorate, or
prevent a disease, disorder, or injury.
Cure

A method or course of medical
treatment used to restore health.
Cure

A method or course of medical
treatment used to restore health.

Don’t forget about prevention (at
least for dominant SCA’s)
Treatment

-Symptomatic
    -pain, cramps, depression, mobility
-Disease-modifying
    -slowing the rate of progression
  “Why Don’t We Have A
 Treatment for Ataxia Yet?”
-Developing a treatment is HARD
  “Why Don’t We Have A
 Treatment for Ataxia Yet?”
-Developing a treatment is HARD
-Expectations for treatments can be
unrealistic
  “Why Don’t We Have A
 Treatment for Ataxia Yet?”
-Developing a treatment is HARD
-Expectations for treatments can be
unrealistic
-We are doing a good job, but …
  “Why Don’t We Have A
 Treatment for Ataxia Yet?”
-Developing a treatment is HARD
-Expectations for treatments can be
unrealistic
-We are doing a good job, but …
- … there are certainly ways to
facilitate treating ataxia
  Clinical Disease




Treat Human Disease
  Clinical Disease

    Etiology (Cause)


    Model Disease


      Treat Model



Treat Human Disease
  Clinical Disease

   Etiology (Cause)

    Model Disease


     Treat Model



Treat Human Disease
  Clinical Disease

   Etiology (Cause)


    Model Disease


     Treat Model



Treat Human Disease
  Clinical Disease

   Etiology (Cause)


    Model Disease


     Treat Model


Treat Human Disease
           Clinical Disease

            Etiology (Cause)


            Model Disease


              Treat Model

                               Treat Symptoms
Treat Human Disease
                                Treat Disease
What is needed to develop effective
 treatments?
1. Knowledge of the disease pathophysiology
2. A way to measure the disease
3. An understanding of the natural history of the
   disease
4. Research Infrastructure
What is needed to develop effective
 treatments?
1. Knowledge of the disease pathophysiology
     -the cause –
        -ataxia genes galore
        -downstream consequences, e.g
        mitochondrial dysfunction in FRDA
        -insights into cerebellar (dys)function
What is needed to develop effective
 treatments?
1. Knowledge of the disease pathophysiology
     -the cause
     -relevant models
        -mice, fruit flies, worms, etc.
What is needed to develop effective
 treatments?
1. Knowledge of the disease pathophysiology
     -the cause
     -relevant models
     -candidate treatments
        -EPI-743, pioglitazone, lithium,
        riluzole, VEGF
          FRDA Timeline                         Treatment Trials



                                          Natural History
                                          Studies Begun



                                          Outcome
First clinical                            Measures
description               Gene Discovered Validated




   1863           1980      1990         2000         2010
What is needed to develop effective
 treatments?
1. Knowledge of the disease pathophysiology
     -the cause
     -relevant models
     -candidate treatments
2.A way to measure the disease
     -clinical scales, instrumented
        measures, biomarkers
What is needed to develop effective
 treatments?
1. All the preliminary info:
       -the cause
       -relevant models
       -candidate treatments
2. A way to measure the disease
3. An understanding of the natural
   history of the disease
     -rate of progression
     -variability
What is needed to develop effective
 treatments?
1. All the preliminary info:
       -the cause
       -relevant models
       -candidate treatments
2. A way to measure the disease
3. An understanding of the natural history of the disease
       -rate of progression
       -variability
4. Research Infrastructure
      -ataxia centers
      -$$$
      -research subjects
IS THIS TREATMENT EFFECTIVE?
IS THIS TREATMENT EFFECTIVE?
IS THIS TREATMENT EFFECTIVE?
                                    Lynch, D. R. et al. Arch Neurol 2010;67:941-947.



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How can the likelihood of a
positive trial be improved?
   How can the likelihood of a
   positive trial be improved?
1. Reduce variability
        -large numbers
        -homogeneous study population
        -precise measures
   How can the likelihood of a
   positive trial be improved?
1. Reduce variability
         -large numbers
         -homogeneous study population
         -precise measures
2. Increase trial timeline
   How can the likelihood of a
   positive trial be improved?
1. Reduce variability
         -large numbers
         -homogeneous study population
         -precise measures
2. Increase trial timeline
3. Use a more effective treatment
   How can the likelihood of a
   positive trial be improved?
1. Reduce variability
         -large numbers
         -homogeneous study population
         -precise measures
2. Increase trial timeline
3. Use a more effective treatment

Note: These are not always possible
       What can be done to
        facilitate treatment
          development?
1. Learn from other diseases
ALS
ALS vs. ataxia
-ALS is 90% sporadic; pathophysiology
not well understood
-Quicker progression, more definite
clinical measures
       What can be done to
        facilitate treatment
          development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
     -non-sexy treatments ARE available

        -(e.g. ALS PEG tubes and
         ventilatory support)
       What can be done to
        facilitate treatment
          development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
     -non-sexy treatments ARE available
       What can be done to
        facilitate treatment
          development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
     -non-sexy treatments ARE available
3. Never underestimate the power of
dedicated action
       What can be done to
        facilitate treatment
          development?
1. Learn from other diseases
2. Don’t disregard low lying fruit!!!
     -non-sexy treatments ARE available
3. Never underestimate the power of
dedicated action
                   Thanks


-Patients, families
-Coordinators: Bettye Robinson RN, Sue Gronka RN
-Colleagues
-NAF, FARA, MDA, NIH

				
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posted:8/31/2012
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