Researchers have begun nationwide clinical trials for a new treatment for diabetes based largely on the discoveries of a professor at Eastern Virginia Medical School (EVMS) in Norfolk.
Doctors hope to reverse diabetes by stimulating the body to produce its own insulin.
In the trial, patients will be injected with a small, specialized section of a protein, called a peptide. In tests on animals, researchers found that the peptide travels to the pancreas, where it apparently “wakes up” inactive adult stem cells, said EVMS’s Dr. Aaron I. Vinik, who pioneered the treatment on animals.
Once stimulated, the formerly sleepy cells give birth to new beta cells, which are responsible for manufacturing insulin. The peptide also seems to trigger the creation of companion cells in the pancreas, which begin making glucagon and other hormones needed to regulate blood glucose.
People with diabetes either can’t produce or can’t properly handle insulin, which helps move glucose out of the bloodstream and into cells of the body, where it can be used for energy. Vinik’s research partner,
Dr. Lawrence Rosenberg of McGill University in Montreal, speculates that diabetes also may occur when the body fails to produce the protein the researchers have identified, called INGAP, or islet neogenesis gene associated protein.
Because diabetes involves such a basic problem, it affects almost every major part of the body and can lead to blindness, heart disease, stroke, kidney failure and nerve damage.
Scientists believe type 1 diabetes, sometimes known as juvenile diabetes, results when the body’s immune system mistakes beta cells for foreign invaders and destroys them. Individuals with type 2 diabetes—which accounts for 90 to 95 percent of cases—may be able to produce insulin initially, but their bodies can’t process it well enough to keep them healthy. Over time, their beta cells can wear out.
Vinik discovered the gene that makes beta cells, and EVMS patented it three years ago. INGAP is a protein made by that gene. From the INGAP protein, Vinik has isolated the peptide that seems directly involved in stimulating the creation of new beta cells.
The INGAP gene is active when a fetus is in the womb, but it then shuts off after birth, although the body normally continues to replenish beta cells here and there throughout a person’s life.
Essentially, Vinik’s research involves turning back the clock. By introducing part of a naturally occurring protein, doctors aim to trick pancreatic cells into acting like they’re back in the womb.
“It’s recreating the whole of what’s created in your mother’s womb,” Vinik said. “We’re lighting up the body’s own adult stem cells, instead of taking them from something else. “
Initial trials of this technique will be performed on 62 adult patients at three medical institutes around the country: the Texas Diabetes Institute at the University of Texas in San Antonio, the Diabetes Care Center at the University of North Carolina at Chapel Hill and the MedStar Research Institute in Washington, D.C.
Vinik has tested the INGAP peptide on hamsters and mice. In his most recent work, all four diabetic mice began producing insulin after treatment.
But producing insulin is only one of the problems.
Doctors don’t yet know if INGAP peptide therapy could ease some of the threatening side effects of diabetes, such as damage to tiny blood vessels in the eyes and kidneys, Rosenberg said.
In humans, doctors will inject the drug into study participants’ muscles once a day for 35 days, Vinik said. Trials began December 5, 2001.
The study, known as a phase I/2a trial, will measure the drug’s safety, tolerability and early trends that might suggest its effectiveness. Researchers will watch this small group of patients carefully for potential negative side effects. They’ll also try to measure which dosages work best.
Vinik himself will not be involved in testing INGAP, a process he expects to conclude by this summer. If all goes well, he’d like to test the therapy on hundreds or even thousands of people around the country.
The research is being funded by a corporate partner, GMP Companies, Inc., a private business based in Florida. GMP and EVMS, which joined forces last year, will share the profits if INGAP one day leads to a successful commercial drug. EVMS earlier had formed a licensing agreement with Eli Lilly Co., which was canceled in 1999.
Scott Campbell, vice president of research at the American Diabetes Association, described Vinik’s work as promising and novel, but he said it’s far too early to know if it will work.
About 70 percent of drugs pass the first phase of FDA trials, Campbell said. Of those, only 30 percent make it through phase 2 trials, which involve more people and which measure efficacy. And of those, only 25 to 30 percent make it through phase 3 trials, which involve hundreds or thousands of people.
Bringing a new drug to market can cost anywhere from $200 million to $400 million, Vinik said.
Many other scientists are attacking diabetes with different approaches.
Doctors in Edmonton, Canada, last year used pancreatic cell transplants to cure the disease—at least temporarily—in several adults.
But the limited number of organs and tissue available for transplants falls far short of the needs of the more than 16 million people with diabetes in the United States. Patients who receive transplants need anti-rejection drugs for the rest of their lives, to prevent the immune system from attacking the foreign tissue.
Stem-cell researchers also hope to produce insulin-secreting cells in the laboratory in order to transplant them back into the body. If successful, Vinik’s technique could offer several advantages over stem-cell therapy, Campbell said.
Injecting INGAP peptides eliminates the lengthy and difficult process of extracting stem cells from embryos, culturing them in a lab, coaxing them to differentiate into pancreatic tissue and stimulating them to make insulin.
Only last year, Vinik said he wanted to cure diabetes within five years.
Today, he said he doesn’t want to make any promises, although he still dreams of seeing a cure for the disease within his lifetime.
“If what we’ve done in animals applies to humans,” Vinik said, “we have a real shot.”