There’s a new way to prevent the onset of type 1 diabetes with an old drug. Methyldopa has been treating high blood pressure in pregnant women and children for more than 50 years, but in a decade-long study, researchers from the University of Colorado Anschutz Medical Campus introduce a new way to put this drug to good use.
"We can now predict with almost 100 percent accuracy who is likely to get type 1 diabetes," explained Aaron Michels, PhD, from the University of Colorado. "The goal with this drug is to delay or prevent the onset of the disease among those at risk.”
In studies with animal models of type 1 diabetes and a clinical trial with 20 people with the disease, Michels and others successfully showed how methyldopa can prevent onset of type 1 diabetes in 60 percent of people at risk for the disease. This percentage of people have a specific molecule, DQ8. The presence of DQ8 significantly increases an individual’s likelihood of developing type 1 diabetes. The adaption of methyldopa to type 1 diabetes marks the first personalized treatment for the disease.
With its connection to the risk of developing type 1 diabetes, researchers theorized that by blocking DQ8, they could prevent the onset of the disease. They used a supercomputer to assess thousands of drugs for their ability to bind DQ8.
"All drugs have off-target effects,” Michels explained. "We took every FDA-approved small molecule drug and analyzed HLA-DQ8 binding through a supercomputer. We searched a thousand orientations for each drug to identify those that would fit within the DQ8 molecule binding groove."
Methyldopa blocks DQ8 but also leaves the immune system alone, making it a particularly good candidate for preventing type 1 diabetes. As an autoimmune disease where the immune system mistakenly attacks beta cells, which produce insulin, many existing treatments for type 1 diabetes involve suppressing the immune system. While those drugs may reduce the immune attack on beta cells, they also leave the individual taking the drug vulnerable to infections.
In addition to preventing and treating type 1 diabetes, methyldopa is also potentially applicable to other autoimmune diseases connected to DQ8. For example, rheumatoid arthritis, celiac disease, multiple sclerosis, and lupus could all be impacted by drugs that block DQ8.
Going forward, Michels and his team will be continuing their study of methyldopa in the context of type 1 diabetes with a larger clinical trial to begin in the spring.
The present study was published in the journal Journal of Clinical Investigation.