Rare Daily Staff

Axovant Gene Therapies reported dosing the first patient in a clinical study of its investigational gene therapy, AXO-AAV-GM1, for the treatment of GM1 gangliosidosis, a progressive and fatal lysosomal storage disorder.

The patient experienced no initial complications related to the intravenous administration of the vector. The dosing marks a milestone as the first patient with GM1 gangliosidosis to be treated with a gene therapy.

GM1 gangliosidosis is caused by mutations in the GLB1 gene leading to impaired production of the beta-galactosidase enzyme. It leads to neurodegeneration, muscle weakness, enlarged liver and spleen, and skeletal abnormalities. Depending on the severity of the condition and time of onset, it can be associated with a much lower life expectancy. There are currently no approved treatments for the disorder.

AXO-AAV-GM1 delivers a functional copy of the GLB1 gene via an adeno-associated viral (AAV) vector, with the goal of restoring β-galactosidase enzyme activity for the treatment of GM1 gangliosidosis. The gene therapy is delivered intravenously, which has the potential to broadly transduce the central nervous system and treat peripheral manifestations of the disease as well.


Preclinical studies in murine and a naturally-occurring feline model of GM1 gangliosidosis have supported AXO-AAV-GM1’s ability to improve β-galactosidase enzyme activity, reduce GM1 ganglioside accumulation, improve neuromuscular function, and extend survival. Axovant expects initial data from the clinical study in the second half of 2019, as well as continued enrollment of patients in this program throughout 2019.

The endpoints of the clinical study include safety, biomarker, neurodevelopment, and magnetic resonance imaging and spectroscopy measures.

The clinical study of AXO-AAV-GM1 is being conducted at the National Institutes of Health, by Cynthia Tifft, deputy clinical director at the National Human Genome Research Institute, and a leading expert in ganglioside storage disorders. A three-way cooperative research and development program among Axovant, the NIH, and the University of Massachusetts Medical School has been established to support the conduct of the clinical program.

“GM1 gangliosidosis is a devastating disease in young children, for which there are no currently approved treatment options,” said Tifft. “The development of a safe and effective gene therapy for these patients would be a welcome advancement in the field of pediatric lysosomal storage disorders affecting the brain.”

AXO-AAV-GM1 is Axovant’s third investigational gene therapy program to enter the clinic. Axovant, part of the Roivant family of companies, is also developing gene therapy candidates that target GM2 gangliosidosis (including Tay-Sachs disease and Sandhoff disease), Parkinson’s disease, oculopharyngeal muscular dystrophy, amyotrophic lateral sclerosis, and frontotemporal dementia.

Photo: Cynthia Tifft, deputy clinical director at the National Human Genome Research Institute

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