Subject: Peptide Vaccine?

From: "Ross M. Greenberg" <[email-masked]>
Date: Sat, 5 Oct 1996 08:56:00 EDT

This looks pretty interesting....

====

APn  09/30 1559  Multiple Sclerosis

By MALCOLM RITTER
 AP Science Writer
   NEW YORK (AP) -- An experimental vaccine enabled multiple sclerosis patients
to build up a police squad of blood cells to stop vandalism in their nervous
systems, and that kept sufferers from getting sicker, a study found.
   Scientists tested the vaccine against a kind of MS that gets progressively
worse over months or years. None of the six patients who built up police-like
cells in the blood got worse during the yearlong study, while 10 of 17 other
patients did.
   The study had so few patients that it couldn't prove the vaccine would be
useful. But experts said the vaccine's effect on the immune system was
encouraging.
   "It's not a universal treatment at this point and should not be considered
so until we have evidence in a lot more patients," said the study's author,
Arthur Vandenbark, of the Veterans Affairs Medical Center in Portland, Ore.,
and the Oregon Health Sciences University.
   About 300,000 Americans have MS. They have such symptoms as unusual
tiredness, loss of balance and muscle coordination, slurred speech, tremors and
difficulty walking. In severe cases, they are partly or completely paralyzed.
   The vaccine was tested against chronic-progressive MS, which accounts for
about 15 percent of cases.
   Nobody knows what causes MS. But scientists do know that the immune system
mistakenly attacks the protective sheath around nerves in the brain and spinal
cord. That causes the symptoms. This vandalism is caused by certain blood cells
called T cells, which gang up at the sites of destruction.
   People with MS naturally have some police-like T cells that can turn the
vandalizing ones off, but not enough of them, Vandenbark said.
   So his vaccine was aimed at getting the immune system to churn out more of
these police T cells. Patients got the vaccine or a placebo injected weekly for
four weeks, then monthly for 10 months. Researchers tracked them for a year.
   The vaccine mimicked a piece of a protein carried by some vandal cells. When
it was injected, the police cells noticed the sharp rise in the number of these
telltale protein pieces. In response, the police cells multiplied.
   Five of nine patients who received one form of the vaccine showed a rise in
their levels of policing T cells. A sixth patient showed the same result from
another vaccine form.
   In contrast to most of the other patients, these six retained their
abilities over the yearlong study in tests of walking speed and use of hands
and arms.
   In four of the six patients, the number of vandal T cells in the blood
dropped. The two others had low levels to start with.
   Abe Eastwood, director of the research and grants program at the National
Multiple Sclerosis Society, called the vaccine "a very promising and
interesting idea." But he said it's too soon to say whether it will be a useful
treatment, since only six patients showed a response.

RTw  09/30 1754  Experimental MS vaccine stabilizes some patients

    By Joanne Kenen
     WASHINGTON, Sept 30 (Reuter) - An experimental vaccine for multiple
sclerosis (MS) appears to have halted or slowed the progressive neurological
disease in about half the patients who took part in a small study, researchers
said on Monday.
     The vaccine is designed as a therapy, not as a way of preventing MS. The
hope is that if patients are treated early, the disease can be stopped in its
tracks through a vaccine alone or through a vaccine combined with drugs.
     "What you are looking for is not turning back the clock but stopping
things from getting worse," Dr. Dennis Bourdette, co-author of a research paper
appearing in Tuesday's edition of the journal Nature Medicine, said in a
telephone interview.
     Bourdette works at the Veterans Affairs Medical Centre in Portland,
Oregon, and the MS Clinic at Oregon Health Sciences University.
     MS occurs when some cells in the immune system start attacking myelin, the
insulation around nerve cells.
     In a year-long double-blind study, a synthesized peptide, or compound
formed from amino acids, was tested on 23 patients with progressive MS.
     Only about half the patients injected with the peptide vaccine had an
immunological response to it. The vaccine boosted the number of "good" immune
cells in their blood and inhibited the disease-causing ones.
     And all six patients with an immunological response also had a clinical
response -- their disease remained stable for a year.In contrast, 10 of the 17
people who did not have a response or who received a placebo got worse,
according to clinical measurements.
     Whether the patients who did not respond to the vaccine would have if a
different peptide had been used is not yet known.
     Biotech company Connective Therapeutics of Palo Alto, California,
announced on Monday that it planned to conduct larger-scale, longer-term
studies of the vaccine.
     About 250,000 people in the United States have MS. Two drugs have been
approved to give partial control of the disease, and a third is near approval.
None is a cure.
     MS usually strikes in young adulthood. About 60 percent of patients are
women, and 40 percent men. Although the pace and pattern of the disease varies
widely, many patients gradually lose muscle control.
  REUTER

UPn  09/30 1738  UPI Science News

   WASHINGTON, Sept. 30 (UPI) -- An experimental vaccine to treat multiple
sclerosis looks promising in a small test on humans, researchers said Monday.
   The so-called T-cell peptide-reactive vaccine does not prevent the disease
but is designed to treat people who already have symptoms, said Dr. Arthur
Vandenbark from the Veterans Affairs Medical Center in Portland, Ore. MS eats
away the myelin sheaths around nerve cells, ruining the central nervous system
of those with ms.
   The vaccine, in development for years, has passed another milestone: the
first double-blind test on humans, in which neither the researcher nor the 23
volunteers knew who was getting a real vaccine and who was getting the placebo.
   After a year of tracking the patients, doctors discovered that the six
people whose immune systems registered a response to the vaccine had remained
in stable health. In contrast, the disease progressed in 10 out of the 17
people who either had not responded on an immunological level to the vaccine or
had been taking the placebo.
   Vandenbark said he looked on "the small pilot trial as a proof of
principle," showing that the general approach to the vaccine would work. He and
colleagues announced their results in the journal Nature Medicine.
   The researchers are trying to reduce the body's population of rogue T-cells
that attack and destroy the myelin sheaths. The vaccine seems to boost the
population of another kind of T-cell that regulates the rogues.
   "They have looked at a novel way of treating autoimmune diseases," commented
Stephen Reingold, vice-president of research and medicine at the National
Multiple Sclerosis Society.
   He cautioned against overinterpreting such early work. Clinical results from
just one year are difficult to interpret in a progressive disease like multiple
sclerosis, he said, and he's looking forward to tests with more patients.
   However, he praised the approach for its potential in focusing treatment on
parts of the immune system that malfunction in multiple sclerosis without
disrupting other immune functions.
   "It's a promising step," Reingold said.
   The early version of the vaccine was indeed very focused, said Vandenbark
and speculated that he may need to other components to broaden the effects to
more patients. "A cocktail is where we're headed," he said.

OTC  09/30 1752  Connective Therapeutics'  Collaborator Reports ...

PALO ALTO, CALIF. (Sept. 30) BUSINESS WIRE -Sept. 30, 1996--Connective
Therapeutics, Inc. (NASDAQ:CNCT) announced today that results from Phase I/II
clinical testing of T-cell Receptor (TCR) peptide vaccines for the treatment of
multiple sclerosis will be published in the October 1996 issue of the journal
Nature Medicine.
   The results from this pilot study indicated that patients who responded
immunologically to TCR vaccines experienced stabilization of disease without
side effects during one year of therapy.
   The Phase I/II physician-sponsored study was conducted by a team of
scientists led by Connective's collaborator, Arthur A. Vandenbark, Ph.D. of
Neuroimmunology Research, Veterans Affairs Medical Center, Portland and Oregon
Health Sciences University.
   The double-blind, placebo-controlled trial involved 23 patients with
chronic, progressive multiple sclerosis who were treated for 12 months with a
native or substituted version of a V beta 5.2 TCR peptide vaccine or placebo.
Successful peptide vaccination boosted protective T-cells and lowered
pathogenic T-cells thought to cause the disease.
   "These promising early data support our decision to conduct additional
studies in a larger population of progressive multiple sclerosis patients,"
said W. Scott Harkonen, M.D., senior vice president of Product Development and
Operations at Connective.  "We believe these clinical observations in multiple
sclerosis generated by Dr. Vandenbark's group also serve as indications of the
potential therapeutic value of TCR technology as a platform to develop vaccines
for other autoimmune and connective tissue diseases."
   In the Phase I/II study, all TCR peptide vaccine responders (6/6) were
clinically improved or stable, while only 7 of 17 non-responders were improved
or stable.  There were no responders in the placebo group.  The vaccines were
well-tolerated, with no evidence of adverse events attributable to TCR peptide
treatment.
   Additional findings in the Nature Medicine report suggest that protective
(regulatory) cells elicited by the vaccine not only inhibit their specific
target pathogenic T-cells, but also inhibit "bystander" pathogenic T-cells in
the area of inflammation in the nervous system.
   This information implies that the target T-cells need only represent a
fraction of the total pathogenic population for the vaccine to be effective --
an important finding as multiple sclerosis is believed to be caused by a
heterogeneic (mixed) population of T-cells.
   The publication of this data coincides with Connective's plans to submit an
Investigational New Drug Application to conduct a Phase I/II study of native
and substituted TCR V beta 5.2 peptide vaccines in progressive multiple
sclerosis.  The study will be a multicenter, double-blind, placebo-controlled
trial which is expected to enroll 100 patients. Connective plans to compare the
immunogenicity of the two vaccines against placebo.
   Dr. Vandenbark commented, "We are excited about the potential of TCR
vaccines as therapies for multiple sclerosis and look forward to participating
in Connective's upcoming trial.  Boosting the body's natural immunity with
vaccines such as these may provide long-term clinical benefit by arresting
disease progression."
   As with other vaccines, the TCR technology is being developed to help the
body recognize and destroy pathogens.  In the case of autoimmune diseases, the
pathogens are believed to be T-cells.  TCR vaccines are manufactured from the
receptor portion of pathogenic T-cells and injected into the patient to elicit
a heightened immune response against the T-cells thought to cause autoimmune
disease.
   Connective Therapeutics' TCR peptide vaccines are being designed to boost
the naturally occurring control arm of the immune system believed to function
inefficiently in immune-mediated diseases. These vaccines are expected to
elicit a "regulatory immune response" that can immunize against the activity of
disease-causing immune cells, possibly arresting the autoimmune disease process
at its earliest stage.
   Connective Therapeutics, Inc., headquartered in Palo Alto, California, is
focused on the development of novel therapeutics for serious connective tissue
disorders.  The company has four products in development: gamma interferon for
atopic dermatitis and keloids; betamethasone mousse for scalp psoriasis and
other scalp dermatoses; ConXn(TM) (recombinant human relaxin H2) for
scleroderma and other fibrotic indications; and TCR peptide vaccines for
rheumatoid arthritis and multiple sclerosis.
   Special Note: This news release contains forward-looking statements that
involve risks and uncertainties that could cause actual results or events to
differ materially from those in such forward-looking statements.  Potential
risks and uncertainties include, without limitation, those mentioned in
Connective's prospectus dated January 31, 1996 under the heading "Risk Factors"
and in Connective's Report on Form 10-Q for the quarter ended June 30, 1996
under the heading "Additional Factors That May Affect Future Results."
   --30--ap/sf
   CONTACT:  Connective Therapeutics Inc.
     Sylvia Wheeler, 415/843-2857
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Business Wire's full file on the Internet  with Hyperlinks to your home page.
URL: http://www.businesswire.com

Copyright 1996

UPn  09/30 1713  UPI Science News

   WASHINGTON, Sept. 30 (UPI) -- An experimental vaccine to treat multiple
sclerosis looks promising in a small test on humans, researchers said Monday.
   The so-called T-cell peptide-reactive vaccine does not prevent the disease
but is designed to treat people who already have symptoms, said Dr. Arthur
Vandenbark from the Veterans Affairs Medical Center in Portland, Ore. MS eats
away the myelin sheaths around nerve cells, ruining the central nervous system
of those with ms.
   The vaccine, in development for years, has passed another milestone: the
first double-blind test on humans, in which neither the researcher nor the 23
volunteers knew who was getting a real vaccine and who was getting the placebo.
   After a year of tracking the patients, doctors discovered that the six
people whose immune systems registered a response to the vaccine had remained
in stable health. In contrast, the disease progressed in 10 out of the 17
people who either had not responded on an immunological level to the vaccine or
had been taking the placebo.
   Vandenbark said he looked on "the small pilot trial as a proof of
principle," showing that the general approach to the vaccine would work. He and
colleagues announced their results in the journal Nature Medicine.
   The researchers are trying to reduce the body's population of rogue T-cells
that attack and destroy the myelin sheaths. The vaccine seems to boost the
population of another kind of T-cell that regulates the rogues.
   "They have looked at a novel way of treating autoimmune diseases," commented
Stephen Reingold, vice-president of research and medicine at the National
Multiple Sclerosis Society.
   He cautioned against overinterpreting such early work. Clinical results from
just one year are difficult to interpret in a progressive disease like multiple
sclerosis, he said, and he's looking forward to tests with more patients.
   However, he praised the approach for its potential in focusing treatment on
parts of the immune system that malfunction in multiple sclerosis without
disrupting other immune functions.
   "It's a promising step," Reingold said.
   The early version of the vaccine was indeed very focused, said Vandenbark
and speculated that he may need to other components to broaden the effects to
more patients. "A cocktail is where we're headed," he said.

- --
Ross M. Greenberg       Virus Acres                  914-586-1700
[email-masked]     New Kingston, NY 12459  Fax: 914-586-2025

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