Progress in Tay-Sachs gene therapy
Tay-Sachs disease is caused by mutations in HEXA gene. Patients experience rapid neurodegeneration, including loss of neurons and decrease in myelination, and usually die before the third year of life. There is no cure for Tay-Sachs and there are no clinical trials investigating genetic intervention.
Gene therapy for Tay-Sachs is currently tested in expanded access study – FDA’s pathway for experimental drugs aimed at life-threatening conditions. Two infants, aged 7 and 30 months, received one-time administration of adeno-associated viruses (rh8) containing healthy HEXA and HEXB genes. Currently, patients are 4 and 11 months after the procedure, respectively.
Younger individual started therapy before the onset of severe symptoms. At 11 months of age, the brain demonstrated normal development. Patient did not enter rapid clinical regression, which should be expected in a typical course of the disease.
Older individual maintained baseline neurological levels over almost one year.
Both patients have slightly higher concentration of Hex A enzyme in cerebrospinal fluid, up to 1.8% of normal enzyme activity.
The study is conducted by Axovant Gene Therapies. Preliminary data were presented at the conference of European Society of Gene and Cell Therapy. The company plans to start phase II clinical trial.