Four-Drug Mixture Reverses Type 1 Diabetes in Mice – Curing Type 1 diabetes
Call it the scientist’s version of happy hour: A new, four-drug cocktail has shown a novel ability to reverse established Type 1 diabetes in some mice, University of Florida Health researchers have found.
Fifty percent of mice that were treated with the four drugs had their established diabetes go into remission, according to the findings. The drug cocktail also succeeded in reversing new-onset cases of Type 1 diabetes in 83 percent of the mice. But it’s the drugs’ effectiveness with established cases that is particularly encouraging because that has the most potential to translate into helping human patients, said Michael Haller, M.D., an associate professor of pediatrics in the UF College of Medicine and a pediatric endocrinologist with the UF Diabetes Institute. The findings were published recently in the journal Diabetes.
About 4 percent of people with diabetes — or 1.25 million people in the United States — have Type 1, according to the American Diabetes Association. In Type 1 diabetes, the immune system attacks and destroys insulin-producing cells in the pancreas.
The research team studied four groups of 12 mice, including one group that was given the four medications. Half of the mice with established diabetes that got the four-drug combination went into remission and maintained a normal blood sugar level for four months, they found.
While diabetes treatments are more easily achieved in mice and effective results can be difficult to replicate in humans, Haller said the four drugs’ overall effectiveness shows considerable promise that is worthy of further study. The four-drug cocktail has an impressive ability to induce disease remission in mice, especially since established Type 1 diabetes typically destroys the overwhelming majority of insulin-producing beta cells, researchers said.
“There are not many things that can produce a 50 percent reversal rate in mice with established Type 1 diabetes, so this is striking and has us all excited about its potential,” Haller said.
Haller said he and the other researchers considered a multidrug approach because single-drug treatments have not been especially effective against Type 1 diabetes. Two of the four drugs were already known to be effective in treating the disease and researchers wanted to build on that, Haller said.
The four-drug combination also offers other advantages. All of the drugs that were tested already have U.S. Food and Drug Administration approval for other uses in humans. Haller said the four-drug treatment would still need close scrutiny as a diabetes therapy, but the expensive and time-consuming process of getting federal regulators’ approval to use the drugs individually in humans is already done. The combination treatment also may be more translatable to human clinical trials because it uses a lower dose of the drug thymoglobulin, which researchers said makes it safer and causes fewer side effects.
In addition to thymoglobulin, the other drugs tested were granulocyte-colony stimulating factor, a dipeptidyl peptidase IV inhibitor and a proton pump inhibitor. When used together, the four drugs have a synergy that makes them substantially more effective than they are individually, researchers found. The study did not determine why the four-drug cocktail was effective in some mice but not others.
“We think combination therapies are the way to move forward with trying to prevent and ultimately reverse Type 1 diabetes. There’s a long way to go, but the results in our animal model give us hope that we’re moving in the right direction,” Haller said.
Next, Haller said he would like to consider a pilot trial of the four-drug combination in the next few years. Before that, he plans to focus on his current trial involving a two-drug treatment for new-onset Type 1 diabetes. Depending on those findings, researchers could then start looking at testing therapies involving more than two drugs, he said.
Health-e-Solutions comment: This potential treatment for #CuringType1Diabetes is, as the researcher described, “a long way off.” The fact that most “cures” in mice do not translate the same to humans means there is much left to prove before we can get very excited about the potential.
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