Gene Therapy for Diabetics?
The problem with juvenile diabetes (Type I) seems simple 'not enough insulin' but trying to replace
it is not. Insulin therapy is imperfect. Though it manages the disease, it does not prevent severe long term complications
such as heart disease, blindness, and nerve deterioration in hands and feet. Recent studies show that these
complications can probably be prevented, if glucose levels are precisely controlled minute by minute.
Part of the problem is that injecting insulin does not mimic the normal process because insulin normally
secreated by the pancreas in response to food intake (glucose levels), is initially passed through the liver,
which removes much of the insulin before it is generally circulated. Islet transplants, successfully being
pioneered by U of A Heritage researchers, are one possible solution to diabetes. However, because of expense and rejection problems,
this will likely not be a suitable therapy for everyone.
Dr. Irene Wanke has another promising solution. She is genetically engineering the liver to serve as a pancreas.
She has taken a pro-insulin gene, attached it to a glucose-regulated part of another gene, and
injected it into liver cells, where it produces pro-insulin. (In the body, pancreatic enzymes convert pro-insulin to insulin.)
Will this insulin be the same as natural human insulin?
Most exciting, the pro-insulin is produced in response to glucose levels. Though other researchers have engineered
genes so that other non-pancreatic tissues produce insulin, none have succeded in getting the gene to
turn on in response to glucose, so insulin is produced as needed.
The engineered gene produces insulin in animals, and ongoing tests will determine how well the gene responds
to glucose levels.
Can liver ensymes process pro-insulin to convert it to insulin? Dr. Wanke expects they can, if she modifies at least
one other gene. Will the insulin be the same as natural human insulin? That will be the next big question.
Patient trials of the gene therapy are a long way off, but the potential is exciting. AHFMR is happy
to bet on Dr. Wanke's chance of succeeding, for she is a person of uncommon enthusiasm for life.
"I like nothing more than to fly into a country and have th unpredictable happen. I really enjoy that
part of travel and its counterpart in science."
AHMFR supported five years of her research while she completed specialty training in endocrinology, and
and a Ph.D. with Dr. Otto Rorstad. The gene therapy project was begun under a MRC Fellowship
with Dr. Norman Wong, a Heritage Medical Scholar at the U of C.
During this time, she not only recieved awards for her studies, she did what many researchers
are afraid to do. She stepped out of the competitive research stream to take time for other aspects of life.
She gave a year of international service at the Davao Medical School in the Philippines, and had three
children, Jacqueline, one-year old, and Christopher and Kimberley, two-and-half-year-old twins. What's
her secret? "A great husband and a great nanny, and the Grace of God," she says.
Dr. Irene Wanke is a Heritage Clinical Investigator at the
University of Calgary, Alberta, Canada.