New research into off-label uses for a 50-year-old drug commonly prescribed for high-blood pressure has found that it could prevent the onset of type 1 diabetes. The promising research also suggests a new approach for investigating drugs that could help treat a variety of autoimmune diseases.
Up to 60 percent of people at risk of developing type 1 diabetes possess a molecule dubbed DQ8. The new study, from researchers at the University of Colorado and the University of Florida, set out to investigate whether blocking that specific molecule could also block the onset of type 1 diabetes and whether there was an already approved drug that achieved this effect.
"We took every FDA approved small molecule drug and analyzed HLA-DQ8 binding through a supercomputer," explains Aaron Michels, one of the researchers working on the project. "We searched a thousand orientations for each drug to identify those that would fit within the DQ8 molecule binding groove."
The research homed in on a drug called methyldopa, which has been safely prescribed to both adults and children for over 50 years to treat cases of hypertension. After proving the drug did specifically block DQ8 in studies with mice, the next step was a phase 1 trial involving human subjects with type 1 diabetes to evaluate both dose safety and efficacy in reducing DQ8 levels in target patients.
As a proof-of-concept early clinical trial, the results were promising. Methyldopa was seen to reduce insulin-specific T-cell responses in patients with recent-onset type 1 diabetes indicating the drug could be effective in preventing development of the disease. A larger clinical trial, slated to get underway this year, is the next step for the researchers.
Another compelling outcome from the research is the potential for the same investigative process to be transferred to other diseases. Simply altering the molecular targets should allow the computer to analyze whether other currently approved drugs could have beneficial off-label uses.
"This study suggests that the same approach may be adapted to prevent autoimmune diseases such as rheumatoid arthritis, coeliac disease, multiple sclerosis, systemic lupus erythematosus and others," says David Ostrov, another researcher on the project.
The new study was published in the Journal of Clinical Investigation.
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