Study suggests L-DOPA therapy for Angelman syndrome may have both benefits and unanticipated effects

Last year a clinical trial of L-DOPA — a mainstay of Parkinson’s disease therapy — was launched for Angelman syndrome, a rare intellectual disorder that shares similar motor symptoms such as tremors and difficulty with balance. The clinical trial is based on a 10-year-old case report showing benefit with the drug, but few studies since have explored the neurological justification for using L-DOPA to treat parkinsonian features in Angelman syndrome.

New research from the University of North Carolina School of Medicine, conducted in animal models of the disorder, now provides justification for this therapeutic approach. The study, published online ahead of print on Nov. 12 by the Journal of Clinical Investigation, suggests that L-DOPA could compensate for a loss of the neurochemical dopamine in the brain’s motor pathways and improve motor symptoms. However, it also indicates that the drug could add to an already increased amount of dopamine in the brain’s reward pathways and thus have unanticipated consequences on emotion and attention.

“The results were extremely surprising, because we don’t know of any other disorder where dopamine is affected one way in one brain pathway and the opposite way in another,” said Benjamin D. Philpot, PhD, associate professor of cell biology and physiology at UNC.

“If what we see in humans mirrors what we see in mice, then it does provide some optimism that L-DOPA might provide benefit for tremor,” said C.J. Malanga, MD, PhD, associate professor of neurology at UNC. “But it also raises caution that researchers might want to consider assessing other aspects of Angelman syndrome that might be affected by dopamine — not just motor symptoms but also other neuropsychiatric features.”  Malanga and Philpot are senior authors of the study.