Treatment for Diabetes Could Have Devastating Side
Effects
86% of the diabetic mice they treated with peptide
immunotherapy died.
New research reveals that a prospective treatment
for autoimmune diseases such as diabetes and multiple
sclerosis can result in serious side effects in
mice. The researchers from Stanford University
found that
86% of the diabetic mice they treated with peptide
immunotherapy died as a result.
In an effort to treat type 1 diabetes small molecules,
known as peptides, are being developed to mimic
the cells that trigger the autoimmune response.
The idea
of this immunotherapy is to trick the body into
tolerating the cells that it would otherwise
attack by "training" the
immune system to ignore the insulin producing cells
instead of killing them.
Earlier work had shown peptides derived from
a protein known as GAD 65, which is expressed
in
the insulin-producing
cells in the pancreas, could be used to reduce
the incidence of diabetes in mice that are
genetically programmed to develop diabetes
(NOD mice). This
approach
was thought to work by inducing a form of "tolerance" and/or
by inducing a type of immune response that can be
associated with allergic reactions.
Rosetta Pedotti and Maija Sanna and their colleagues
from Stanford University investigated whether
the injection of relatively large amounts
of GAD 65
peptides into NOD mice might be effective
in inducing tolerance
and whether it caused any side effects. Their
results were published in open-access journal
BMC Immunology.
The researchers injected the GAD 65 peptides
into the abdomen of NOD mice each week
for 3 weeks.
Unfortunately, the potential therapeutic
benefits of this treatment
could not be evaluated because of an unanticipated
side effect of the treatment. When the
researchers gave the mice one further injection
with
the GAD 65 peptide preparation, 4 weeks
after the
original
3 week course of treatment, all of these
mice developed a severe allergic reaction
causing
86% of them
to die within 30 minutes. In contrast,
mice that had
not received any previous peptide injections
showed no adverse reactions.
Peptide immunotherapies are currently being
studied in phase I and phase II clinical
trials for both
type 1 diabetes and multiple sclerosis.
In contrast to the devastating side effects
seen in mice,
only minor allergic reactions were observed
in clinical
trials on more than 200 patients and
these were limited to around 10% of patients.
The
frequency
of minor
reactions is similar to that seen with
approved peptide-based drugs like Copaxone.
These
results have been published
in peer-reviewed journals (for example,
Kappos et al., Nature Medicine, October
2000).
Peptide immunotherapy has the potential
to improve the lives of people at risk
from
developing asthma
or autoimmune diseases - from patients
with type 1 diabetes to multiple sclerosis
sufferers.
But
the safety of the treatment must be
paramount. Pedotti,
Sanna and colleagues recognize the
potential of this therapy but stressed that "great care must be
taken" when attempting to suppress any autoimmune
diseases using peptide immunotherapy. These conclusions
are strengthened by earlier work from the same researchers
using mice that were induced to have symptoms of
another autoimmune disease, an animal model of multiple
sclerosis.
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The Average Dinner Plate Size in 2003 is 10.5”
