Personalized medication is increasingly common, and with the results of a study published in March in the Journal of Clinical Investigation, the applicability of using a patient’s own genetic make-up as a target to prevent diabetes has become even clearer. Earlier research established that individuals expressing human leukocyte antigen HLA-DQ8 serotype have an increased risk for type 1 diabetes, and that this serotype is also commonly linked to other autoimmune disease.
Dr. Aaron Michels, associate professor of medicine at the University of Colorado Anschutz Medical Campus and one of the study researchers, theorized that if the DQ8 molecule could be blocked, the onset of illness could be stopped. “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,” said Michels, adding, “This is the first personalized treatment for type 1 diabetes prevention.”
Surprisingly, after analyzing thousands of drugs with the supercomputer, they found that the antihypertensive agent methyldopa blocked DQ8. Methyldopa was first available in the 1960s and has remained a popular, preferred option for treating hypertension during pregnancy. A competitive inhibitor for DOPA decarboxylase, methyldopa reduces dopaminergic and adrenergic activity in the peripheral nervous system, lowering blood pressure. Michels and University of Florida (UF) Health researcher David Ostrov, PhD, describe their shared goal of seeing this same mechanism of action helping to treat other autoimmune diseases, including diabetes. “This study has significant implications for treatment of diabetes and other autoimmune diseases,” said Ostrov, associate professor of pathology, immunology and laboratory medicine in the UF College of Medicine and a member of the UF Health Cancer Center, Genetics Institute, and Center for NeuroGenetics.
Dr. Ostrov said the 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. The next step will be a larger clinical trial sponsored by the National Institutes of Health, planned this spring.
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