GM2 gangliosidosis
GM2 gangliosidosis is caused by mutations in one of two genes which contain the instructions for making the protein ‘beta-hexosaminidase A’. This protein is responsible for breaking down other proteins in a subcellular structure known as a ‘lysosome’, which may be thought of as a sort of ‘recycling centre’ for the cell. People in whom beta-hexosaminidase A does not function correctly as a result of these genetic mutations experience a variety of neurological symptoms as cellular proteins are not broken down correctly and build up to toxic levels in the brain. Beta-hexosaminidase A is composed of both an ‘A’ and ‘B’ subunit, the instructions for which are contained in two different genes. Depending on whether the mutation occurs in the ‘A’ gene or ‘B’ gene, GM2 can also be known as either Tay-Sachs or Sandhoff disease. The fact that Tay-Sachs and Sandhoff disease are each caused by mutations in single genes makes them amenable to gene therapy; a type of therapy in which a modified virus is used to deliver ‘corrected’ versions of the A and B beta-hexosaminidase genes into a patient. This press release from the pharmaceutical company Sio Gene Therapies Inc reports that the first patient with infantile-onset Tay-Sachs disease has been dosed in a Phase 1/2 clinical trial designed to test how well a GM2 gangliosidosis gene therapy works. The therapeutic is known as AXO-AAV-GM2, and is the first ‘disease-modifying’ treatment for GM2 gangliosidosis, meaning it has potential to slow, stop or potentially even reverse the progression of disease. Up until now, the only treatments available are those designed to help manage symptoms. This trial will, in the first stage, assess safety and the most effective dosing regiment for AXO-AAV-GM2. The second stage will involve further evaluation of safety and how effective the treatment is. Although much further work is needed to determine how effective AXO-AAV-GM2 will be at treating GM2 gangliosidosis, results from previous ‘expanded access’ clinical studies indicates that it will be both well-tolerated in patients and associated with good clinical outcomes.