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Collaboration to advance therapy for Huntington’s Disease

Neil A
Neil Aronin 

UMass Medical School has entered into a research collaboration with pharmaceutical company Lundbeck Inc. aimed at further development of a targeted therapy to slow or halt the progression of Huntington’s disease (HD). 

Led by Neil Aronin, MD, professor of medicine, cell biology and physiology, the collaboration will further the study of RNAi-based therapies as a possible method for selectively suppressing the abnormal protein that causes HD, called mutant huntingtin (mHtt). RNA interference, or RNAi, is a natural process that cells use to turn down, or silence, activity of specific genes. HD is mapped to a specific gene, which makes it a promising target for RNAi-based therapy because production of a mutant protein such as mHtt can potentially be blocked by knocking down, or reducing, the gene’s activity. 

There is currently no therapy to stop or reverse the course of HD, a hereditary neurodegenerative disease characterized by progressive motor, cognitive and emotional symptoms. 

“Our core idea is that RNAi can be used to selectively reduce mutant huntingtin production to slow or block the progression of HD, but we also hypothesize that excessive huntingtin silencing may impair neuronal function by interfering with essential signaling events,” said Dr. Aronin, principal investigator of the study. “This research collaboration allows us to test promising RNAi-based therapeutic vehicles to selectively knock down mutanthuntingtin with the goal of restoring normal neuronal function.” 

This multi-faceted, pre-clinical study will progress beyond previously successful animal-model studies and could bring RNAi-based therapy one step closer to human clinical trials. The study will measure dosing, assess the safety profile and establish the best distribution of RNAi, packaged as short hairpin RNA (shRNA), via adeno-associated virus for potential use in clinical HD therapies. This method is used to interfere with the expression of a specific gene and, in this case, researchers will apply it to mHtt. 

Other UMMS faculty collaborating with Aronin include Guangping Gao, PhD, the Penelope Booth Rockwell Chair in Biomedical Research and professor of microbiology and physiological systems, and Richard P. Moser, MD, professor of surgery and radiation oncology. Other collaborators include colleagues at Massachusetts General Hospital, University of Pittsburgh School of Medicine and the Neuro-Psychiatric Institute at UCLA. 

This collaboration is part of Lundbeck’s Huntington’s disease research initiative, which is driven by collaborations with academic institutions and companies with promising compounds in development. 

Read more about efforts underway to bring RNAi into the clinical setting: