RNA Innovation Seminar: Hayley McLoughlin, Neurology

“Antisense Oligonucleotides for Ataxia”
Hayley McLoughlin, Ph.D.

Assistant Professor of Neurology
Assistant Professor of Human Genetics
University of Michigan

In-person: BSRB, ABC seminar rooms / hybrid link

Abstract: Her talk will cover recent advances in antisense oligonucleotide (ASO) therapy with a particular emphasis towards their mechanistic and therapeutic applications in Ataxia. She will specifically discuss ASO approaches in the most common dominantly inherited ataxia, Spinocerebellar ataxia type (SCA3). SCA3 is one of nine polyglutamine expansion diseases and is caused by a gain-of-function repeat expansion in the disease gene, ATXN3. To date, there is no effective treatment for this relentlessly progressive and fatal neurodegenerative disease. Throughout her postdoctoral training in Dr. Paulson’s lab and into her independent research career, she has assessed the efficacy and tolerability of anti-ATXN3 ASO gene silencing therapy in SCA3 mouse models in collaboration with Ionis Pharmaceuticals. Published in successive cross-sectional (PMC5415970) and longitudinal studies (PMC6119475), they defined the first evidence of a gene therapy mitigating both pathological and behavioral disease phenotypes in the SCA3 mouse, which overexpresses the full-length human disease gene. These anti-ATXN3 ASOs are currently begin assessed in SCA3 human subjects through a Phase 1 clinical trial driven by Biogen for pharmacokinetics and safety (ClinicalTrials.gov Identifier: NCT05160558).