http://bmj.com/cgi/content/full/323/7324/1272
BMJ 2001;323:1272 ( 1 December )
Judy Siegel-Itzkovich
Scientists have developed the world's first drug that successfully halts the
immune system's destruction of pancreatic b cells in humans. Called
DiaPep277, the drug offers the possibility of preventing type I
diabetes in healthy people with a genetic risk of the disease and
halting its progression in people whose b cells have already begun
to die.
The research team, led by Professor Irun Cohen of the Weizmann Institute of
Science's department of immunology, proved that three injections of
DiaPep277 given within six months of diagnosis of type I diabetes
successfully arrested the progression of the disease in newly diagnosed
patients. Participants did not show any harmful or major side
effects, and none left the study.
"It remains to be seen if, and at what intervals, additional DiaPep277
treatments might be needed to maintain long term endogenous insulin
production," Professor Cohen said.
A report on the study, conducted at Hadassah University Hospital in
Jerusalem, was published last week (Lancet 2001;358:1749-53).
With phase II trials on DiaPep277 successfully completed, phase III trials
are due to begin in various centres around the world in the middle
of next year. Peptor, the biopharmaceutical company that purchased
the rights, is planning to present an application to the US Food and
Drug Administration in 2004.
Professor Cohen, Dr Dana Elias (at the time of the study a postdoctoral
fellow at the Weizmann Institute and now vice president for research
and development at Peptor), and colleagues have worked for more than
a decade on the vaccine. It was tested on patients at the Hadassah
University Hospital by Professor Itamar Raz, president of the Israel
Diabetes Association and head of the hospital's diabetes unit.
The researchers worked on a small peptide fragment known as p277, despite
widespread scepticism among other scientists in the field about its efficacy.
Results from a mouse model were dramatic, and the team proceeded to
show p277's efficacy in patients, 200 of whom have been treated
successfully so far in Israel, England (in phase I trials at St
Helier Hospital in Morden, Surrey), Hungary, Bulgaria, and Germany.
On the basis of the results of the research, Peptor developed DiaPep277 to
prevent or treat type I diabetes. The phase II study was conducted
on 35 patients aged 16 to 55 who were newly diagnosed
with type I diabetes.
Eighteen patients received injections of DiaPep277 at the beginning of the
study, at one month, and at six months; 17 patients received
three injections of an inert placebo. Patients in the treatment
group showed a halt or delay in the attack on, or destruction of,
their b cells on a follow up examination 10 months after the first
injection.
The results were evident in the level of insulin production in the body and
in a decreased need for insulin injections. The researchers were
able to trace the mechanism of this improvement to changes in the
patients' T cells.
In contrast, patients who received the placebo showed a significant decline
in their natural insulin production and a continual increase in the
need for injected insulin.
"In children, the destruction of pancreatic cells is very rapid, taking
place even in a couple of months," added Professor Raz.
"People who have a genetic risk for the disease and who are exposed
to a specific virus, toxic material, or food are likely to develop
type I diabetes."
Phase II trials on children aged seven to 16 showed an improvement,
said Professor Raz, but the result was not significant. "This
is not because the treatment can't be effective in children; but
since the destruction of pancreatic cells in children is so rapid,
you have to identify the children and give them the peptide as a
preventive measure or catch them no later than two weeks after the
destruction begins." Dr Elias, of Peptor, said that this
strategy is now being used in younger children.
For several years Professor Cohen and his team have been studying the
mechanism by which the immune system destroys the pancreatic cells
that produce insulin.
Working with mice, the scientists discovered that a particular protein,
called HSP60, was closely linked to this destruction. The protein
acts like an antigen, prompting the immune cells to attack. Further
investigation showed that injecting diabetic mice with p277, a small
peptide fragment of the HSP60 protein, shut down the immune
response, preventing the progression of type I diabetes.
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