IPRD funded research by Deirdre McCarthy
Tay-Sachs disease (TSD) is an ultra-rare genetic disorder caused by mutations in the HEXA gene. The α subunit of lysosomal β-hexosaminidase α (HEXA) enzyme is critical for converting GM2 gangliosides to GM3 gangliosides. When the HEXA enzyme availability is severely reduced an abnormal buildup of GM2 occurs, causing neurological symptoms. Unfortunately, there is no cure for TSD, and treatment options are limited. A recent expanded-access clinical trial used adeno-associated virus (AAV) to deliver the HEXA gene intracerebrally to two patients with infantile TSD. The results demonstrated good overall safety and feasibility of gene therapy for TSD. However, the safety and efficacy was compromised significantly by immune-mediated toxicity. The goal of this project is to test a new generation of AAV vectors that have the potential to evade the host's immune defenses.
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