Multiple Sclerosis

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					                             Multiple Sclerosis
 Multiple Sclerosis (MS) is an autoimmune
disease, whereby the body destroys its own
myelin (protective coating surrounding the
nerves in the central nervous system). Because
the myelin is damaged, messages moving along
the nerve are transmitted more slowly or not at
all.

Areas of damaged myelin can be viewed through
Magnetic Resonance Imaging (MRI) scanning
and are known as plaques. These plaques, or
sites of damage, can cause MS symptoms.

At this time, it is not known what causes MS. It
is known that MS affects approximately one in
one thousand people in North America, usually
in early adulthood (O'Connor, 2002). There are
two main classifications of the disease:
progressive and relapsing remitting. Within
the first classification there are two more


Primary Progressive MS (PPMS) is characterized by a slow and continuous deterioration
from the beginning, while Secondary Progressive MS (SPMS) becomes progressive
following a course of attacks and recoveries. Within the second classification there are
also two differentiations, benign and relapsing remitting. People with benign MS suffer
the least amount of disability and seem to recover fully from their attacks, while people
with relapsing remitting MS (RRMS) do not recover as well from attacks but do enjoy
remissions. The percentage of people suffering from these types of MS at any one time
breaks down to 10 per cent benign MS, 40 per cent RRMS, 10 per cent PPMS, and 40 per
cent SPMS (M.S. Freedman, personal communication, November 21, 2002).

After about ten years, approximately 50 per cent of people with RRMS go on to develop
SPMS (Herndon, 2002). Just as the names imply, this means that the course of the disease
changes from one that is characterized by plateaus and exacerbations (relapsing
remitting) to one that progresses at a steadier rate (secondary progressive). There is some
speculation that RRMS and SPMS are actually the same form of the disease, as 80 per
cent of people who have RRMS go on to the SP stage (O'Connor, 2002). One wonders if
people with RRMS had an infinite amount of time on earth, whether that number would
increase to 100 per cent. It may also be difficult to identify when a person transitions
from RRMS to SPMS. There are currently no definitive tests to help with this kind of
diagnosis.

differentiations, primary progressive and secondary progressive.


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Most current research is devoted to identifying ways that could slow down, or halt the
progress from RRMS to SPMS. In fact, many new drug therapies have been successful in
treating the symptoms of people with RRMS. However, studies have indicated that SPMS
does not respond as well, if at all, to medications used to treat RRMS (Lynch, S.G., 2000;
O'Connor, P. Ed., 2002; Walker J.E., & Margolin, S.B., 2001). Because of the lack of
effective drug therapies for people with SMPS there is a need to find successful
treatments to improve their quality of life.


multiple sclerosis (MS) is the most common neurological disease among young adults. In
most cases, the disease appears between the ages of 20 and 40 years, and in every case, it
lasts a lifetime.

In different people and on different days, its symptoms may range from barely noticeable
to completely disabling.

      Its first symptom is usually a visual disturbance blurred or double vision, red-
       green confusion, or even temporary blindness in one eye.
      Soon, muscle fatigue, pain, numbness, weakness, stiffness, or 'pins and needles'
       develop.
      As the disease progresses, patients may lose coordination, balance, hearing, or
       bladder/bowel control.
      Some endure mild concentration or memory problems, while others experience
       depression, manic-depression, and paranoia.
      Other possible symptoms include sexual dysfunction, tremors, dizziness, slurred
       speech, trouble swallowing, urinary problems, and episodes of facial pain or
       inappropriate emotions.

While most MS patients will not experience all of these symptoms, they will experience
some combination of them at different levels of severity and duration.

There are four types of MS:

      About 85% of MS is relapsing-remitting: Symptoms grow more severe for a few
       days or weeks, and then partially or completely disappear for a random amount of
       time. This pattern continues, alternating between attack and remission.
      Within 10 years, half of those with relapsing-remitting MS develop secondary-
       progressive MS. When this happens, remissions cease and the patient enters a
       steady, gradual decline.
      10% of patients experience a gradual decline from the initial onset of the disease.
       This is called primary-progressive MS.
      Only 5% of MS patients have progressive-relapsing MS, in which they
       experience a gradual decline, yet also suffer attacks of more severe symptoms.

The good news is that MS is almost never fatal. Malignant MS, where a patient becomes
severely disabled or dies shortly after onset, is extremely rare. In fact, just a quarter of


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MS patients ever need a wheelchair, and 90% of
those still walking after five years continue walking
for the next ten.

The bad news is that MS strikes early and lasts a
lifetime, affecting certain groups even more often
than others. For reasons that are not entirely clear,
women, Caucasians, people of Northern European
or Scandinavian descent, and those in temperate
climates (the northern US, Canada, and Europe) are
particularly prone to MS. In all, over 400,000
Americans and 2,500,000 people worldwide suffer
from the debilitating effects of MS.

What causes multiple sclerosis?

The human brain is an extremely complex organ
composed of billions of cells called neurons.
Different groups of neurons perform different
functions, such as controlling movement,
processing sensory information, and making
decisions. Neurons are covered by a protective
padding called myelin. Myelin ensures that messages can travel
down the cell and throughout the brain and body as quickly as possible.

The body is protected by a series of cells, chemicals, and mechanisms that make up the
immune system. During an MS attack, these cells and chemicals strike the brain's neurons
and destroy their myelin. Areas of scarred myelin are called lesions. Lesions disrupt the
                                                  transmission of messages, and cause the
                                                  symptoms of MS.

                                                     Areas of scarred myelin are called lesions. They prevent
                                                  messages from traveling down the cell and throughout the
                                                  brain and body as quickly as possible.

                                                  MS Internatial Foundation


                                                  We don't know
                                                  what causes the
                                                  immune system
                                                  to destroy the
                                                  myelin. Some
                                                  theorize that an
                                                  environmental
                                                  agent, perhaps a
                                                  virus,




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triggers the attack. We also believe that certain genes may predispose individuals to MS,
making some particularly prone to it. The genes that have this effect are still unknown.

How is multiple sclerosis diagnosed?

Because the symptoms of MS are so variable, they are often hard to diagnose. Doctors
might begin by assessing a patient's balance, senses, eye reflexes, and medical history.
Then, they may use an MRI, MRS, evoked potential test, or spinal tap to examine the
body.

      Magnetic resonance imaging (MRI) is a technique used to create images of the
       brain and spinal cord, and detect any potential lesions.
      Magnetic resonance spectroscopy (MRS) examines the brain's biochemistry.
      An evoked potential test measures how fast the brain responds to stimuli.
      A spinal tap checks brain fluid for chemical abnormalities.

Two main criteria must be met in order to diagnose MS.

   1. The patient must have had at least two separate episodes of severe symptoms.
   2. The symptoms must indicate that the disease has affected different parts of the
      brain and spinal cord.

If the doctor cannot make a definitive diagnosis, he or she may call it 'possible MS' or
'probable MS' until further evidence can verify 'definite MS.'

Is there any treatment?

There are treatments available, but there is no cure for MS.

Fortunately for patients, there are drugs that help alleviate its effects. Doctors used to
prescribe steroids to ease the severity of the episodes, but they had risky side effects and
virtually no effect on the long-term progression of the disease.

Now doctors opt for disease-modifying drugs (DMDs). Unlike steroids, DMDs change
the course of MS, slowing its progression and reducing the number of episodes. The
DMDs most commonly prescribed for MS include Avonex, Betaseron, Copaxone,
Novantrone, and Rebif. Such DMDs have proven far more effective than any treatments
of the past.

Avonex is a disease-modifying drug prescribed to treat MS. It works by fighting the
immune system chemicals that destroy myelin.

Betaseron is a disease-modifying drug prescribed to treat MS. It works by fighting the
immune system chemicals that destroy myelin.




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Copaxone is a disease-modifying drug prescribed to treat MS. It works by making the
harmful immune system cells helpful.

Novantrone is a disease-modifying drug prescribed to treat MS. It works by suppressing
the immune system itself, keeping it from attacking both harmful invaders and innocent
myelin.

Rebif is a disease-modifying drug prescribed to treat MS. It works by fighting the
immune system chemicals that destroy myelin.

What research is being done?

We are now aiming to improve these existing medications and to develop other, more
effective treatments. We are also searching for what triggers MS, investigating genetic,
environmental, and immunological possibilities. We hope that some day, this information
will lead to prevention and a cure.

Time is of the essence. The National Institute of Neurological Disorders and Stroke
estimates that MS costs the nation over $2.5 billion every year. More than 200 young
adults are diagnosed each week. Without adequate research and support, these numbers
will only grow.

But the outlook need not be so grim. There are things we can do to lessen the damage of
multiple sclerosis, and to brighten our prospects for the future.

Multiple Sclerosis at the HCNR

This is where the HCNR comes in. By encouraging translational research, the HCNR
accelerates the movement of ideas from the laboratory to therapies for patients. Current
treatments can only slow the progress of MS. Translational research probes deeper,
examining the underlying mechanisms of the disease to develop a cure that strikes at its
cause.

By uniting doctors and researchers from Harvard Medical School and its affiliated
hospitals, the HCNR brings together the community of like-minded investigators needed
to foster translational research and tackle neurodegenerative disease. Working with a
broad spectrum of researchers, we encourage the rapid application of basic neuroscience
discoveries to clinical needs, while reducing duplication and promoting cooperation
throughout the community. This makes the research more efficient and effective, and
greatly increases the chances of finding a cure. For more information about the HCNR,

Below are a few examples of what the HCNR is doing to tackle multiple sclerosis. Click
on the links to learn more about the programs.




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Samples and Specimens
Before translational research can begin, scientists must have an adequate supply of
samples and specimens to study. To fulfill this need, the HCNR's Virtual Brain Bank
(VBB) has compiled over 5,000 samples of human brain, blood, serum, DNA,
cerebrospinal fluid, and antibodies, and sorted them by disease diagnosis, ethnicity,
gender, and age. Now, using a single online search, hundreds of researchers are able to
identify the sample they might need to better understand brain diseases. The Genetics
Outreach counselor is also available to discuss the DNA samples and their implications
for patients and families. In 2003, the VBB was used by 54 investigators for 282 different
searches, while the genetic counselor spent over 193 hours helping investigators and
physicians and over 108 hours counseling and obtaining samples from patients.




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