Diabetes breakthrough! Toronto scientists cure disease in mice
Tom Blackwell, National Post
Published: Friday, December 15, 2006
In a discovery that has stunned even those behind it, scientists at
a Toronto hospital say they have proof the body's nervous system
helps trigger diabetes, opening the door to a potential near-cure of
the disease that affects millions of Canadians.
Diabetic mice became healthy virtually overnight after researchers
injected a substance to counteract the effect of malfunctioning pain
neurons in the pancreas.
"I couldn't believe it," said Dr. Michael Salter, a pain expert at
the Hospital for Sick Children and one of the scientists. "Mice with
diabetes suddenly didn't have diabetes any more."
The researchers caution they have yet to confirm their findings in
people, but say they expect results from human studies within a year
or so. Any treatment that may emerge to help at least some patients
would likely be years away from hitting the market.
But the excitement of the team from Sick Kids, whose work is being
published today in the journal Cell, is almost palpable.
"I've never seen anything like it," said Dr. Hans Michael Dosch, an
immunologist at the hospital and a leader of the studies. "In my
career, this is unique."
Their conclusions upset conventional wisdom that Type 1 diabetes,
the most serious form of the illness that typically first appears in
childhood, was solely caused by auto-immune responses -- the body's
immune system turning on itself.
They also conclude that there are far more similarities than
previously thought between Type 1 and Type 2 diabetes, and that
nerves likely play a role in other chronic inflammatory conditions,
such as asthma and Crohn's disease.
The "paradigm-changing" study opens "a novel, exciting door to
address one of the diseases with large societal impact," said Dr.
Christian Stohler, a leading U.S. pain specialist and dean of
dentistry at the University of Maryland, who has reviewed the work.
"The treatment and diagnosis of neuropathic diseases is poised to
take a dramatic leap forward because of the impressive research."
About two million Canadians suffer from diabetes, 10% of them with
Type 1, contributing to 41,000 deaths a year.
Insulin replacement therapy is the only treatment of Type 1, and
cannot prevent many of the side effects, from heart attacks to
kidney failure.
In Type 1 diabetes, the pancreas does not produce enough insulin to
shift glucose into the cells that need it. In Type 2 diabetes, the
insulin that is produced is not used effectively -- something called
insulin resistance -- also resulting in poor absorption of glucose.
The problems stem partly from inflammation -- and eventual death --
of insulin-producing islet cells in the pancreas.
Dr. Dosch had concluded in a 1999 paper that there were surprising
similarities between diabetes and multiple sclerosis, a central
nervous system disease. His interest was also piqued by the presence
around the insulin-producing islets of an "enormous" number of
nerves, pain neurons primarily used to signal the brain that tissue
has been damaged.
Suspecting a link between the nerves and diabetes, he and Dr. Salter
used an old experimental trick -- injecting capsaicin, the active
ingredient in hot chili peppers, to kill the pancreatic sensory
nerves in mice that had an equivalent of Type 1 diabetes.
"Then we had the biggest shock of our lives," Dr. Dosch said. Almost
immediately, the islets began producing insulin normally "It was a
shock ? really out of left field, because nothing in the literature
was saying anything about this."
It turns out the nerves secrete neuropeptides that are instrumental
in the proper functioning of the islets. Further study by the team,
which also involved the University of Calgary and the Jackson
Laboratory in Maine, found that the nerves in diabetic mice were
releasing too little of the neuropeptides, resulting in a "vicious
cycle" of stress on the islets.
So next they injected the neuropeptide "substance P" in the
pancreases of diabetic mice, a demanding task given the tiny size of
the rodent organs. The results were dramatic.
The islet inflammation cleared up and the diabetes was gone. Some
have remained in that state for as long as four months, with just
one injection.
They also discovered that their treatments curbed the insulin
resistance that is the hallmark of Type 2 diabetes, and that insulin
resistance is a major factor in Type 1 diabetes, suggesting the two
illnesses are quite similar.
While pain scientists have been receptive to the research,
immunologists have voiced skepticism at the idea of the nervous
system playing such a major role in the disease. Editors of Cell put
the Toronto researchers through vigorous review to prove the
validity of their conclusions, though an editorial in the
publication gives a positive review of the work.
"It will no doubt cause a great deal of consternation, " said Dr.
Salter about his paper.
The researchers are now setting out to confirm that the connection
between sensory nerves and diabetes holds true in humans. If it
does, they will see if their treatments have the same effects on
people as they did on mice.
Nothing is for sure, but "there is a great deal of promise," Dr.
Salter said.
