The Diabetes Cure of Tomorrow

Researchers Get Innovative With Diabetes Cure Research

| Dec 1, 2001

Someday, a cure for diabetes will be found. But the question still remains about it how it will happen. By regenerating our own cells? Or maybe by transplanting islets from pigs into humans?

It's anyone's guess at this point. Many outstanding doctors from around the world are working hard to find a cure for the disease. They have persisted in their efforts, and have seen both successes and failures. Regardless, these men and women continue the ongoing struggle to get the funding they need to make the studies happen. Let's take a look at some of the researchers who may now be on the path to a cure.

Re-Training the Immune System

Denise Faustman, MD, of Massachusetts General Hospital, is proposing a treatment to cure diabetes that entails re-training the immune system to stop attacking islets. So far, after 11 years of research, she's shown that the therapy works on mice.

The method "is distinguishing in that it opens up a new therapeutic angle that was not feasible in the past," Dr. Faustman told Diabetes Health.

Publishing the results of her research in the July issue of the Journal of Clinical Investigation, Dr. Faustman and colleagues induced a natural drug called TNF-alpha in diabetic mice to kill the autoimmune cells. Then, they injected mice with healthy donor cells that trained the immune system to leave the islet cells alone instead of killing them off.

"The real miracle that happened—the surprise that was totally unexpected—was that we did get rid of established autoimmunity," she says.

As an unexpected outcome, islet cells re-grew in the mice, providing more insulin production and stabilizing their blood-glucose levels. Up to 75 percent of the mice maintained normal blood-glucose levels for at least 100 days after the treatment.

"The real hero here is the mouse, who re-grew the islets in the pancreas. There is more and more basic science data suggesting that [re-growth can happen] for heart cells and liver cells, but we never really saw it [happen] in diabetes," she says.

Of course, Dr. Faustman would like to proceed with phase 1 and 2 clinical trials, but says the future of her research depends on funding. She currently receives funds from various non-profit sources, but not from funding giants such as the Juvenile Diabetes Research Foundation (JDRF).

Funding aside, Dr. Faustman remains steadfast in her belief that her treatment offers an alternative to more popular research methods for finding a cure. "It's different," she says. "You don't need islets and you don't need stem cells" to cure diabetes.

What About the Obvious: A Vaccine?

Another aspect of diabetes cure research involves catching diabetes before it starts—in other words, developing a vaccine.

Alan Baxter, MD, PhD, and colleagues at the Centenary Institute in Sydney, Australia, say they have discovered a part of the tuberculosis vaccine that may prevent type 1 diabetes.

Tony Basten, director of the Centenary Institute, says the vaccine is promising because it is non-toxic, has been shown to protect against diabetes in mice without causing lupus and has the potential to be administered in a single dose to children who are at high risk for type 1. In addition, "the proposed trials have the support of pediatricians in Sydney responsible for the management of diabetes," Basten told Diabetes Health.

Baxter, who has been working with autoimmunity since 1988, would like to begin conducting the phase 1 and 2 trials for the vaccine, in which dosage, timing, safety and efficacy of the vaccine will be tested. In addition, he has plans for clinical trials to test the vaccine on siblings of people with diabetes who are at high risk for getting the disease.

But Baxter needs more funding to make it happen.

Diabetes Australia, a private Australian charity, first provided funding for his research. Baxter has also received additional funds from an Australian pharmaceutical company, but those funds will only hold him over until the end of the year. A lot of the vaccine research is done on a volunteer basis by students and research staff.

If they can move on with test trials and the trials prove successful, the vaccine could be available in the next five years, Baxter says.

"This treatment has the potential to prevent diabetes in those at risk," Baxter told Diabetes Health. "For those who already have the disease, there may be less concern about their children getting diabetes in the future."

The Islet Cell Argument

One popular—and notably long-running—research method that's aimed at finding a cure for diabetes is islet transplantation, or injecting islets of the pancreas to replace those that have been destroyed. The most significant setback here has been the need to take anti-rejection drugs to stop the immune system from fighting off the foreign cells.

Can lslets Do the Trick?

One man who believes islet transplantation is the answer to finding a cure is Scott R. King, president of Islet Sheet Medical, of San Francisco, California (not the Scott King who founded this magazine). King and his team are collaborating with researchers at the University of Alberta, Edmonton, Canada, to find a way to transplant a sheet of islets without having to use anti-rejection drugs. The Islet Sheet, which contains islets protected by a polymer coating, can be taken out at any time—a measure of safety unavailable with other technologies.

"If the Islet Sheet concept works without significant risk to patients, this could be an incredible advance for islet transplant," James Shapiro, director of the clinical islet transplant program at the University of Alberta, was quoted as saying in the March issue of Diabetes Health.

"Transplant without drugs is the goal of all of us, the dream being to transplant earlier in the course of diabetes, including children one day, to more effectively prevent secondary complications without the risks of [anti-rejection drugs]."

The method has been shown to work in small animal studies and is in the process of being tested in dogs in pre-clinical studies.

But King doesn't have enough funding yet to launch large animal clinical trials.

"I don't think we can make much progress with one or two dogs," he says.

King is soliciting private investors for larger sums of money. He's thinking in the range of seven figures.

"We need several million [dollars] to get into clinical trials," he says. "To get the product on market, [we will need] $100 million."

If the funding happens, King hopes to launch clinical trials in two years.

Despite the long road ahead—the need for large-scale funding and years of further research—King thinks his method is the way to go.

"In three years, islet transplantation has gone from something you barely talked about to being acknowledged [as a viable option]," he says. "I've thought for 20 years that it's the way we were going to cure diabetes, but now I think there's certainly more interest and hope for it."

Look Ma, No Drugs

Gordon C. Weir, MD, head of the section on Islet Transplantation and Cell Biology at the Joslin Diabetes Center, has been working on islet-cell transplantation for more than 10 years. In his latest effort, his research team found a way to transplant islets successfully in mice without having to use anti-rejection drugs—a potential coup in the quest for a cure.

Reporting their results in the August issue of Diabetes, Weir's research team placed bio-compatible capsules made out of alginate—a gel extracted from seaweed—around the islets to protect them from rejection.

Then, they injected the encapsulated islets into the pancreas of mice, allowing survival of the islets for over 350 days. In addition, the mice showed a five- to 10-fold increase in insulin secretion and maintained normal glucose levels, according to the report. To test the efficacy of the islets, they were taken out of the mice. The mice's blood glucose then went back up to higher-than-normal levels.

This technique "prolongs islet survival without" having to suppress the immune system, the researchers concluded.

But Weir is quick to point out the flaws in his method.

"I'm worried about it," he concedes. Translating the procedure successfully from rodents to larger animals—such as dogs and monkeys and, eventually, humans—is not in the least bit guaranteed.

"I have a hard time being optimistic," he says. "I think it's really important to not trumpet [these results]."

Weir and his colleagues have already begun testing their encapsulation technique on monkeys. So far, the results are "disappointing," according to Weir.

"We would be lucky to get this [method] to work," he says.

At the present time, he has enough funding to conduct some of the experiments he'd like to perform. But he is always concerned about being able to continue receiving support. For now, with dollars from Joslin, the National Institutes of Health (NIH) and the JDRF, he's not exactly strapped for cash.

"Most good scientists have been able to obtain funding that allows them to do some of the work they want to do," he says. "But everybody would like more."

Wait, Maybe Pigs Are the Answer

While multiple research centers focus on using human islets to find a cure, one group of investigators at Duke University Medical Center believes that transplanting islet cells taken from pigs could be the answer. The technique called xenotransplantation—using animal tissues to replace human tissue—is banned in the United States and many other countries.

Using pig islets is promising because pigs offer a potentially "unlimited supply of islet cells," according to a press release by Micro Islet Inc., a technology firm in San Diego, California, that has a patent for the transplant method.

Dr. William Kendall Jr., Duke University's senior surgical resident, and colleagues took approximately 250,000 islet cells from pig pancreases that had been coated with alginate to avoid rejection. Then, they injected the encapsulated islets into the abdomen of a baboon with diabetes. The blood-glucose levels of the baboon decreased from 400 mg/dl to an average of 115 mg/dl over the following nine months.

Five additional baboons are now being studied. The encouraging results lead researchers to believe they can conduct human trials within a year, according to Dr. Kendall, who spoke at the June 15 scientific meeting of the International Pancreas and Islet Transplant Association.

In another study, researchers in Mexico transplanted cells from the testes and pancreas of newborn piglets into teenagers with diabetes without having to use anti-rejection drugs.

Dr. Rafael Valdes, MD, and colleagues from the Children's Hospital of Mexico in Mexico City transplanted encapsulated islets that were taken from customized, disease-free piglets. The islets, produced by Diatranz of Aukland, New Zealand, are protected with an alginate coating. Researchers transplanted the islets into 12 teens aged 10 to 15 who had had type 1 diabetes for at least three years. According to Dr. Valdes, who announced the results of the study at the International Xenotransplantation Association Congress in Chicago this October, two of the teens recovered completely from diabetes, three lowered their need for insulin by more than 40 percent and the other teens improved slightly.

Valdes's group plans to conduct further studies to fine-tune the technology, although funding is limited. If the studies work, the technique could become available within the next two years. Not enough is known about the risks, such as spreading animal viruses to humans, according to Britain's The Sunday Times.

All Work and No Payback?

With the decades of cure research behind us and no definitive cure to be found, many people are left wondering when—and if, for that matter—it will happen.

Despite all the hard work, researchers still have faith in the cause and believe that a cure will, indeed, be found.

Working on finding a cure for diabetes "is in the spotlight now," according to Dr. Weir of Joslin. "What we've learned in the past 25 to 30 years [since research to find a cure began], is that it's a really hard problem.

"Sometimes people get discouraged and they say ‘gee whiz, is it really ever going to happen?' I really feel quite certain that it will."

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Categories: Blood Glucose, Diabetes, Diabetes, Insulin, Islet & Pancreas Transplant, The Cure, Type 1 Issues


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