Subject: Report on MULTIPLE SCLEROSIS UPDATE

From: David T. Mintz <[email-masked]>
Date: 12 Dec 1996 15:51:00 GMT

MULTIPLE SCLEROSIS CLINICAL UPDATE 
                           DECEMBER 8, 1996, NYC

Here are some of my impressions of the above update which was
presented by Drs. Weinreb,Raine,Weiner.Grossman,Kupersmith, Knobler
and Herbert, 

1. The animal models of experimental allergic encephalomyelitis now
seem more likely to be truly analagous to human multiple sclerosis,
even though the acute human lesion cannot be studied and the
adhesion molecule noted in animals had not yet been found in
humans(a molecule that seems to facilitate attachment and
penetration of blood-brain barrier by T cells.

2. The multiple cytokines, interferons, and other chemicals
involved in the disease process show a similar pattern in animals
and humans and vary with relapse and remission. 

3. The MRI now has the capability of quantifying the total burden
of disease as well as often identifying an acute lesion. The
previous lack of correlation between the MRI and clinical status
has  lessened considerably.

4. The disease process can now be more sensitively monitored by the
use of serial MRIs and cytokine studies. This may eventually be
invaluable in evaluating therapy accurately and speedily.

5. The disease process involves many steps and could potentially be
blocked at any of these steps. Briefly; Antigen is presented to a
myelin autoreactive T cell(not pathogenic) at a special receptor
site on the cell.   The process is complex and involves
histocompatability(genetic) and costimulatory molecules attached to
the antigen presenting cell. The antigen is probably a foreign
protein produced by a virus or other infectious process, resembling
some component of myelin. At that point the T cell becomes
activated and migrates to the blood brain barrier which it
penetrates.It then congregates around a blood vessel and calls
forth a large number of other T cells and macrophages which attack
the myelin sheath of the brain cells and the oligodendrocytic cells
which make and nurture  the myelin. The secretions that are called
forth by the activated T cells to aid this invasion are
interleukin-2, interleukin-12, interferon gamma, and TNF.
Eventually other activated T cells secreting interleukin-4,
interleukin-10 and  TGF-beta gain ascendancy and down grade the
previous process producing a failure of activation with remission.
Whether the TH1(bad) T cells can be turned into TH2(good) T cells
is under study. 

6. In chronic or secondary progressive multiple sclerosis T cells
remain chronically activated! 

7. Some of the therapies in use or under study are as follows:

     a. Interferon-beta and Interferon-beta-1a: Treatment produces
a significant reduction in relapse rate. Secondary progressive
multiple sclerosis is now under study. Mechanism: Several sites are
affected. Interferon gamma and TNF are reduced.

     b. Copolymer 1: Relapse rate is reduced. Mechanism is
unkown(may increase the suppressor downgrading cells or affect the
antigen presenting site because of its myelin components).

     c. Oral bovine myelin: Relapse rate was reduced in a small
series. No side effects. Mechanism: Oral tolerance of an
autoantigen. A two year controlled trial in relapsing-remitting
disease will be completed this spring

     d. Immunosuppressants:

          1. Cladribine: Still experimental. It may have
significant therapeutic effect, tho its toxicity is likewise
significant. Further studies in chronic progressive multiple
sclerosis are in progress