Press Releases
City MD closes on cure for diabetes
AARON DERFEL
Montreal Gazette
Monday, February 11, 2002
A discovery Dr. Lawrence Rosenberg stumbled upon 20 years ago
at McGill University might prove to be more than just an effective
treatment for diabetes - it could very well be a cure.
After the effects of diabetes were reversed in hamsters, mice
and, most recently, dogs, human trials have begun on Rosenberg's
special insulin producing protein.
"We're not claiming that it's a cure because it sounds too
far-fetched at this point to say that, but certainly in our animal
studies we've cured animals for the last couple of years,"
Rosenberg said. "I mean, really cured."
The concept behind Rosenberg's research is ingenious, if not
deceptively simple. Rather than treat the symptoms of diabetes,
Rosenberg and co-researchers at the Eastern Virginia Medical School
have decided to tackle the root causes of the disease.
Diabetes occurs when the pancreas fails to produce enough of
the hormone insulin to break down sugar in the blood. When that
happens, an excess of blood sugar can cause heart problems, kidney
failure and blindness, and require amputations.
There are about 500,000 diabetics in Quebec, a number that's
expected to double by 2025. And doctors suspect that 40 per cent
of diabetics are unaware of their condition.
To date, the most common treatment for diabetes has been synthetic
insulin injections. There are also glucose sensitizers that make
the use of insulin more effective in the body, and chemicals that
release what little insulin exists in diabetics.
"What we're doing is stimulating the body to do what it
normally does, but we've sort of ramped up the process,"
Rosenberg explained in his cluttered ninth-floor lab at the Montreal
General Hospital.
"We're accelerating the development of new insulin-producing
cells, which are normal cells."
It was while Rosenberg was studying pancreatic cancer at McGill
in the early 1980s that he serendipitously discovered a protein
that triggers the creation of insulin-producing cells, or islets.
Later on, Dr. Aaron Vinik, of the Eastern Virginia Medical School,
found a way of refining the protein, called Islet Neogenesis Gene
Associate Protein (INGAP).
The researchers first tested a cruder form of INGAP on hamsters,
and found that 60 per cent were cured. This past year, Rosenberg
tested a purer form of the protein on lab mice - with a 100-per-cent
cure rate.
A U.S. biotech company that has licensed the protein tested it
on about 48 diabetic dogs, with similarly great results.
"Certainly, in the animals we've got evidence that you can
give this treatment for a period of time and then stop it,"
Rosenberg said of the injectable solution.
What that means is that the lab animals regained the ability
to naturally regulate insulin and no longer required the INGAP
medication.
"If everything goes well, it is quite conceivable that there
would be a therapy on the market within five years," he said.
There are two forms of diabetes: juvenile, or Type I, and adult-onset,
or Type II. For reasons that are still not understood, the immune
systems of Type I diabetics recognize the insulin-producing cells
as foreign and destroy them. Type II diabetes mainly affects people
older than 45, usually as a result of obesity. In their case,
the insulin-producing cells malfunction - partly because they
are damaged by an excess of fat in the bloodstream.
Diabetics must be constantly vigilant about the amount of sugar
in their blood. They must also be careful not to administer too
much insulin for fear of losing consciousness. The standard therapies
are far from a cure; half of all diabetics inevitably develop
complications despite their medication.
"Our hope is that with our treatment - if we can restore
a normal state of affairs with the body regulating itself again
with its own insulin - those secondary complications won't develop,"
Rosenberg said. "Or else we can temper those complications
somewhat so that they're not severe."
The INGAP therapy would also eliminate the need for blood-sugar
tests and insulin injections. The clinical trials now under way
in three U.S. cities are focusing on both types of diabetes.
Mark Lipsett, a graduate student working with Rosenberg, said
the merit of the research is that it doesn't concentrate on the
"tail end" of the disease.
"It's almost like a magic bullet because the body would
build new insulin-producing cells," he said.
"I myself am a Type I diabetic, so finding a way to cure
diabetes is very exciting from a personal context."
At the Montreal General last Friday, Lipsett and Rosenberg isolated
islets from a cadaveric pancreas donated by Transplant Quebec.
The idea behind that work is to collect enough of the cells to
transplant them in the livers of diabetics.
In that regard, Rosenberg said his INGAP research is simply a
more advanced form of the islet transplants. Rather than transplant
islets, Rosenberg's treatment allows the body to naturally regenerate
islets.
How the INGAP molecule triggers the creation of insulin-producing
cells is still a mystery.
One leading theory is that the molecule binds to a receptor in
stem cells of the pancreas and turns them into insulin-producing
cells.
In the laboratory, Rosenberg and his colleagues synthesize INGAP
by "stringing together a certain number of amino acids."
However, they've discovered that a similar protein is found in
the pancreas.
"This is the culmination of 22 years of work," Rosenberg
said. "It's nice to know that you haven't wasted 22 years
of your life doing something.
"In the larger scheme of things, diabetes is a huge health-care
problem that affects millions of people. To think that we have
a therapy that could significantly impact the lives of these people
is just incredible to contemplate."