Researchers find blood pressure drug holds promise for preventing onset of Type 1 diabetes

Researchers working with a University of Florida supercomputer have discovered that a common drug used to control high blood pressure also might help prevent or delay the onset of Type 1 diabetes in up to 60 percent of those at risk of getting the disease.

The finding by researchers at UF Health and the University of Colorado Anschutz Medical Campus were published this week in the Journal of Clinical Investigation.

“This study has significant implications for the treatment of Type 1 diabetes and also other autoimmune diseases,” said David Ostrov, Ph.D., an associate professor in the department of pathology, immunology and laboratory medicine in the UF College of Medicine and a member of the UF Health Cancer Center, the UF Genetics Institute and the UF Center for NeuroGenetics.

“This study suggests that the same approach may be adapted to prevent autoimmune diseases such as rheumatoid arthritis, celiac disease, multiple sclerosis, systemic lupus erythematosus and others,’’ he said.

The implications for those at risk of getting Type 1 diabetes is enormous.

“We can now predict with almost 100 percent accuracy who is likely to get Type 1 diabetes,” said Aaron Michels, M.D., a researcher at the Barbara Davis Center for Childhood Diabetes and an associate professor of medicine at CU Anschutz. “The goal with this drug is to delay or prevent the onset of the disease among those at risk.”

The drug, methyldopa, has been used for over 50 years to treat high blood pressure in pregnant women and children. It is on the World Health Organization’s list of essential drugs. But like many drugs used for one condition, the researchers found it is potentially useful for something totally unrelated.

“This is the first personalized treatment for Type 1 diabetes prevention,” said Michels. “We made this discovery using a supercomputer, on the lab bench, in mice and in humans.”

That supercomputer is the HiPerGator, the most-powerful computer at a public university and the third most-powerful university computer in the nation. HiPerGator has enough memory to store 40 years of high-definition TV video or 240 million books.

Some 60 percent of people at risk of getting Type 1 diabetes possess the DQ8 molecule, which significantly increases the chance of getting the disease. The researchers believed that if they could block the DQ8 molecule, they could also block the onset of the disease.

After running thousands of drugs through the supercomputer, they found that methyldopa not only blocked DQ8, it also didn’t harm the immune function of other cells like many immunosuppressant drugs do.

The research spanned 10 years and its efficacy was shown in mice and in 20 Type 1 diabetes patients who took part in a clinical trial at the Barbara Davis Center for Childhood Diabetes at the University of Colorado School of Medicine.

The next step will be a larger clinical trial sponsored by the National Institutes of Health in spring.

“A drug capable of blocking the unwanted activity of HLA-DQ8 would be expected to prevent autoimmune diabetes in high-risk individuals, such as those inheriting HLA-DQ8, and also delay the progression of the disease in diabetes patients,” Ostrov said.

The study’s authors include Mark Atkinson, Ph.D., the director of the UF Diabetes Institute and a professor in the department of pathology, immunology and laboratory medicine in the UF College of Medicine. Other authors are Aimon Alkanani of the Barbara Davis Center for Childhood Diabetes at CU Anschutz; Kristen McDaniel of the Barbara Davis Center; Stephanie Case of the Barbara Davis Center; Erin Baschal of the Barbara Davis Center; Laura Pyle of the Barbara Davis Center and Colorado School of Public Health; Sam Ellis of the Barbara Davis Center and the department of clinical pharmacy at CU Anschutz; Bernadette Pollinger at the Novartis Institutes for Biomedical Research in Basel, Switzerland; Katherine Seidl at Novartis; Viral Shah at the Barbara Davis Center; Satish Garg at the Barbara Davis Center; and Peter Gottlieb at the Barbara Davis Center.