Gene therapy for Huntington’s disease | LATSS 2026

Speaker: Sarah Tabrizi (Huntington's Disease Centre, UCL) Synopsis: Huntington's disease (HD) is a devastating rare inherited neurodegenerative disease caused by a CAG repeat expansion in exon 1 of the huntingtin gene (HTT) that affects people typically in their early 40s. The disease has a complex pathogenesis which involves somatic expansion of the CAG repeat in vulnerable neurons leading to the production of toxic protein species. HD is now thought of as having a two-step pathogenesis – the rate driver (somatic expansion of the repeat), which is modified by a number of DNA repair proteins. Then step 2, toxicity drivers, mutant Huntingtin exon 1 fragment proteins, and N-terminal proteolytic fragments from full length mutant HTT. This talk will give an overview of HD drug development, including consideration of the evidence needed to transition from preclinical work to first in human trials. It will cover the disease's pathogenesis and trajectory in humans, looking at the new insights within the mechanistic and therapeutic landscapes, with agents targeting huntingtin DNA, RNA and protein including the recent AMT130 gene therapy results. The talk will discuss the diverse therapeutic modalities being tested and give an overview of the current state of clinical development including the future challenges we face treating this complex genetic disease. This talk was recorded at the LifeArc Translational Science Summit 2026. ------------------------------------- LifeArc is a self-funded medical research organisation with one clear purpose – transforming the lives of people living with rare diseases and drug-resistant infections. We aim to deliver this by conducting and funding pioneering research, and working with partners to accelerate the translation of scientific breakthroughs into new tests and treatments. Our vision is a world where people living with rare diseases and drug-resistant infections can access effective, life-changing treatments faster. Find out more at lifearc.org