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Investigators: David Wraith
and Hartmut Wekerle
by John Bonner
Swiss bee-keepers are the unlikely source
of evidence to suggest that a proposed new treatment for multiple
sclerosis will work, said immunologist David Wraith from the
University of Bristol.
Wraith's team has been investigating ways
of blocking the specific T cells that react to proteins of
the protective myelin sheath surrounding nerve cells. The
T cells produce inflammatory cytokines that mediate destruction
of the protective sheath.
He has been using synthetic peptides based
on fragments of myelin protein to induce tolerance and stop
the disastrous autoimmune response.
The approach has been successful in a
laboratory model for human MS, experimental allergic encephalomyelitis.
Repeated exposure to the peptides switches off the Th1 pathway,
which generates T cells that produce tumor necrosis factor
and other cytokines implicated in the inflammatory response
in MS patients.
Treated mice express a different T-cell
population, known as Th0, which produces the protective cytokine
IL-10. This blocks any further autoimmune
degeneration by preventing antigen-presenting cells from activating
new Th1 cells.
The peptides are squirted up the nostrils
rather than given as an intravenous vaccine. This
makes use of the mucosal immune response designed to prevent
damaging inflammatory reactions to harmless antigens in the
air and (in the gut mucosa) in food.
"Most autoimmune diseases are inflammatory
responses, and so we are tapping into the machinery which
has been specially designed to dampen down the inflammatory
process," Wraith told BioMedNet News.
Even antigens that are otherwise harmful
can be tolerated when presented to the immune system via the
mucosal surface. Scientists in the mid-19th century described
how Native Americans had devised a way of preventing skin
reactions to poison ivy by regularly eating the plant's leaves,
Wraith says.
But, Wraith needed evidence
that the beneficial changes induced by the vaccine in mice
could also be generated
in humans. "It is all very well having an
animal model. But before we could think of trying this approach
on patients, we needed evidence that people could produce
the same type of T cells that generate the protective IL-10
response seen in mice."
That evidence came from a study of beekeepers
in Switzerland, which showed that regular
exposure to bee stings switches off allergic reactions
- the bee-keeper's blood samples were rich in IL 10.
Wraith has an agreement in principle
from the UK medicines licensing authority to begin trials
in MS patients. These are likely to begin within the next
year, after completing the necessary preclinical safety tests.
Patients will probably receive a primary course of repeated
weekly doses followed by monthly booster doses. He expects
those patients in the early stages of the disease to benefit
most.
Current
treatments for MS do little more than treat the symptoms of
the disease.
Even the controversial beta interferon
therapy works only in some patients and then only slows the
progress of the disease. "We hope that we can shut the
gate - this is the only treatment that gets to the heart of
the process that causes the disease," he said.
Bio
Med Net News
July 27th, 2001
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