Subject: Hopes for another MS breakthrough

From: Gabriella <[email-masked]>
Date: Sun, 4 Aug 1996 20:41:45 EDT

This is all that I received from Prof.Thwaite in response to a request for more
information regarding the radio interview as posted a couple of weeks ago.

The intervew transcript was posted to the Technion MS List on Mon, Jul 15, 1996
in the thread: "New develpoment?"

Gabriella [[email-masked] ]

--------------- Forwarded Message ---------------
~From:   Cliff Jeal, INTERNET:[email-masked]
Cc:     INTERNET:[email-masked]
~Date:   Wed, Jul 24, 1996, 04:42

RE:     MS breakthrough

Research in Multiple Sclerosis in the Department of Pathology and Microbiology,
University of Bristol (UK)

What is Multiple Sclerosis (MS)?  MS is a disease affecting the myelin sheath
which  surrounds nerve axons in the central nervous system (CNS).  Myelin serves
to  insulate the nerve axons thus helping them to work effectively.

MS is believed to be an autoimmune disease.  This means that the immune system,
which normally functions to defend the body against infectious agents such as
viruses and bacteria, turns against the body itself and, in the case of MS, now
attacks the myelin sheath.

What are the current treatments for MS?  At present there is no cure for MS.
Since  this is an autoimmune disease, one preferred option has been to treat
with immune  suppressive drugs.  These drugs can control the progression of but
unfortunately  do not cure the disease.  A great deal of interest has been
expressed in the use of  beta-interferon.  This drug does not provide a cure for
MS but does reduce the  number of relapses suffered by patients with
relapsing-remitting disease.  As with  all immune suppressive drugs,
beta-interferon is not without side-effects but it  offers hope that disease
progression may be contained, at least in the short-term.   The aim of our
research in MS is to understand how the disease arises and thereby  find a more
specific way of treating this complex disease.

Why does MS arise?  Research in many laboratories has now established that T
lymphocytes of the immune system are centrally involved in this and other
autoimmune diseases.  These cells develop in the thymus of the body where they
undergo a strict selection or schooling process.  This is designed to ensure
that  cells with the potential to attack the body, or misbehave, are filtered
out.  Clearly  some T cells escape the filtration process and have the potential
to cause diseases
such as MS.  Precisely what triggers T cells to attack myelin in any one
individual is  not known and is an area of intensive research.

Will it be possible to re-educate T cells once they have left the thymus?
Recent  research from the immunology laboratories in Bristol has shown that it
is indeed  possible to switch off potentially harmful T cells.  The idea for
developing such a  new treatment arose from advances in our understanding of the
way in which T  lymphocytes work.  These cells only become dangerous following
their activation
by small fragments of protein, known as peptides.  Further work has shown that
these peptides can suppress autoimmune responses depending on how they are
introduced to the body.  A number of routes of administration have proven
effective  and among these the nasal route is looking particularly promising.
This means that  treatment of diseases such as MS might simply involve sniffing
a small amount of  solution containing the appropriate peptide.

MS is a complex disease and probably involves many different T cells with
specificity for many peptides.  Initially it was thought that it would be
difficult to  treat such complex diseases with simple peptides.  Recent work has
shown,  however, that, as long as you choose the right one, a single peptide can
suppress  the immune response to a whole range of peptides and even to myelin
itself.

Is there a drug ready now?  This is a new discovery which has arisen from 10
years  of laboratory work in this country and the U.S..  It is now time to
screen as wide a  group of MS patients as possible in order to allow us to
choose the right peptide for  a clinical trial.  The design of the peptide will
be crucial.  Our recent work has shown
that simple modification of one of its building blocks can dramatically improve
the  efficacy of a peptide for switching off autoimmune T cells.

How long will all this take?  We hope to have identified the best peptides
within two  years.  As peptides are being identified they will be modified to
improve their  efficacy and concurrently tested for safety.  As soon as safe and
effective peptides  are developed they will be processed for clinical trials.

Work carried out in this laboratory is supported by grants from the Multiple
Sclerosis Society of Great Britain and Northern Ireland.

David C Wraith
(e.mail: [email-masked])

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