From: "Michael Watkins"
<MICHAELW at ksg1.harvard.edu>
To: "Autoimmune Research"
<Autoimmune_Research at ksg1.harvard.edu>
Date: Fri, 26 Jan 1996 17:34:34 EST
Reply-to: Autoimmune_Research at ksg1.harvard.edu
Some exciting new research was
reported yesterday in the journal
Nature
This message contains the summary of the
article from Nature, and two press releases
Treatment of experimental
encephalomyelitis with a peptide
analogue of myelin basic protein
Nature 379, 343-346 (1995)
Summary from Nature
Experimental encephalomyelitis
is an autoimmune disease in mice
which serves as a model for multiple
sclerosis in humans. Brocke and
co-workers show that peptide
analogues of myelin basic protein
can be used to reverse the symptoms
of the disease. The therapeutic effect
of the peptides is inhibited by
antibodies to IL-4, suggesting that
it may be mediated by the induction
of Th2-type T cells. Such cells could
inhibit the Th1 responses commonly
associated with inflammation. S Brocke,
K Gijbels, M Allegretta, I Ferber, C
Piercy, T Blankenstein, R Martin, U Utz,
N Karin, Ling, P J Fairchild, D C Wraith,
A O'Garra, C G Fathman & L Steinman
STANFORD, Calif.--(BUSINESS WIRE)--
Jan. 24, 1996--A new study points
researchers toward a promising treatment
for people with multiple sclerosis (MS).
The study suggests that a single
agent may halt the immune system's
attack on nerve cells that leads to
MS, and that clinicians can clear
patients' brains of destructive T
cells by treating the patients
with a single peptide. Until now,
researchers had suspected that a
complex mixture of many compounds
might be necessary to halt the symptoms
of the disease, which affects about one
in 1000 people in the United States.
The finding will be published in the
Thursday, Jan. 25 issue of Nature, in an
article by a team including researcher Dr.
Stefan Brocke, professor of medicine Dr.
Gary Fathman, professor of neurology Dr.
Lawrence Steinman, and postdoctoral fellow
Dr. Koenraad Gijbels, all at Stanford;
and researcher Dr. Anne O'Garra at DNAX
Research Institute in Palo Alto.
The finding is based on studies of
mice with a disease researchers believe
models multiple sclerosis. In multiple
sclerosis, cells in the body's immune system
attack and destroy the protective sheath
that covers nerve fibers in the brain and
spinal cord. This causes symptoms ranging
from numbness and tingling to paralysis and incontinence.
Researchers can induce the multiple
sclerosis-like disease in mice by injecting
them with myelin basic protein, a main
component of the protective sheath.
T cells in the mouse's immune system attack
the foreign myelin basic protein as well as
the protein in the myelin that coats the
mouse's own nerves, thus causing the disease
known as experimental autoimmune
encephalomyelitis (EAE). In the model,
the T cells' initial attack is triggered
by a small segment of the myelin basic
protein, called a peptide, said Brocke,
the article's lead author.
Researchers have found that once the
disease is established, other peptides in
myelin basic protein begin triggering attacks
by groups of T cells, each group tailored to
attack a different peptide, said Brocke, a
researcher in Stanford's neurology department.
Until now, researchers suspected that a
cure would have to be a complex mixture of
elements designed to fend off each of the
different groups of T cells swarming the
nerve tissue, Brocke said.
In the study, the researchers found
that they could reverse the influx of
T cells by exposing the cells to just
one particular peptide. This peptide
triggered the withdrawal of all groups of
invasive T cells from the brain.
"What we did was this: We induced a
multiple sclerosis-like disease in mice
and then treated the established disease
by injecting them with a solution containing
a small portion of the protein that causes
the disease. We found that the mice got
better -- their paralysis subsided,"
said Brocke, who performed experiments
in hundreds of mice.
"Since we can reduce this variety
of T cells without using multiple
therapeutics, it looks like we have
a nice suppressive agent in our hands," Brocke said.
Several drug companies, including
Neurocrine Biosciences Inc., are
attempting to use the peptide to develop
a multiple sclerosis treatment and are
carrying out clinical trials, Brocke said.
Steinman is Neurocrine's chief scientist
of neuroimmunology.
The same general strategy might be
successful in treating other autoimmune
diseases, such as arthritis and diabetes,
Brocke said.
The Stanford and DNAX researchers
collaborated with others at the National
Institute of Neurological Disorders and
Stroke; the Max-Delbrueck Centrum for
Molecular Medicine in Berlin; the Weizmann
Institute of Science in Rehovot, Israel;
Neurocrine Biosciences Inc. in La Jolla
and Cambridge University in Cambridge, England.
The research was funded in part by
the National Institute of Neurological
Disorders and Stroke, the Phil N. Allen
Trust and the Wellcome Trust.
CONTACT:
Stanford Medical Center News Bureau
Rosanne Spector, 415/725-5374 or 415/723-6911
KEYWORD: CALIFORNIA
INDUSTRY KEYWORD: MEDICINE
BIOTECHNOLOGY EDUCATION
SAN DIEGO, Jan. 24 /PRNewswire/ --
Neurocrine Biosciences, Inc. today
announced that an investigational
multiple sclerosis (MS) treatment
reverses paralysis in animal models
as reported in tomorrow's issue of
Nature (vol. 379, no. 6563, pages 343-345).
Scientists at Neurocrine, Stanford
University and The National Institutes of
Health (NIH), in an article titled,
"Treatment of Experimental Encephalomyelitis
With a Peptide Analogue of Myelin Basic
Protein," have designed a peptide that
binds specifically to the disease-causing
T cells in the plaques of MS patients'
brains, turning them off and reversing
the inflammatory cascade, thereby reversing paralysis.
"This is a significant development
in MS research. It is the first time a
complex autoimmune process has been
completely shut down with a specific
immunomodulator peptide which targets
only a small percentage of the disease-
specific cells," according to the article's
lead author, Lawrence Steinman, M.D.,
Chief Scientist of Neuroimmunology of
Neurocrine, Professor of Neurological
Sciences at Stanford University, and
Professor of Immunology at The Weizmann Institute.
MS is an inflammatory disease of the
central nervous system that destroys the
protective myelin sheath insulating nerve
cells. This occurs when T cells, immune
cells that normally patrol the body for
pathogens and tumors, inappropriately
attack the myelin sheath. This disease
affects between 250,000 and 350,000 people
in the United States and over 1.1 million
worldwide. The usual age of diagnosis is
between 20 and 40 years old, and like many
autoimmune diseases, strikes twice as many women as men.
"MS is a devastating chronic
neurodegenerative disease with no cure.
Because current MS therapies show only
limited efficacy in slowing disease
progression, there is a need for innovative
new treatments," said Steve Hauser, M.D.,
a leading multiple sclerosis clinician at
the University of California, San Francisco
Medical School (UCSF).
Dr. Steinman and several academic labs
around the world have identified the region
housing the dominant protein within the
myelin sheath that is targeted by the
autoimmune T cells, called myelin basic
protein (MBP). Neurocrine has developed
an altered peptide from a region of MBP
that has the ability to deactivate the
T cells attacking the myelin sheath.
"Ideally, one would be able to
silence or remove only the part of
the immune system that is self-destructive
and leave the rest of the immune system
intact to fight infection," said Dr. Steinman.
"By focusing on T cells that cause the
autoimmune disease, we appear to be able
to come much closer to accomplishing this
than researchers previously thought possible."
"Neurocrine believes that this
approach can be used in many intractable
autoimmune diseases including diabetes,
rheumatoid arthritis and uveitis," said
Gary Lyons, President and CEO of Neurocrine.
"Given the substantial progress Neurocrine
has made in the past year, we anticipate
initiating clinical trials for the treatment of MS in 1996."
Neurocrine's MS research has been
carried out under an established Cooperative
Research and Development Agreement (CRADA)
with the laboratories of Dr. Roland Martin
and Dr. Henry McFarland at NIH and is
sponsored in part by a grant from the
Small Business Research program.
Neurocrine Biosciences, Inc.,
headquartered in San Diego, is a
neuroimmunology biopharmaceutical
company integrating medicinal chemistry
and molecular biology to develop and
commercialize small molecule therapeutics
to treat diseases of the central nervous
and immune systems including multiple
sclerosis, Alzheimer's disease, stroke
and psychiatric disorders.
CO: Neurocrine Biosciences, Inc.
ST: California
IN: MTC
SU:
