Jordi Diaz-Manera, MD, PhD, Professor of Neuromuscular Diseases at Newcastle University discusses the latest results from an ongoing phase1/2 clinical trial testing gene therapy for late-onset Pompe disease.

Pompe disease is a lysosomal disorder due to an inadequate level of the enzyme acid alpha-glucosidase (GAA) that results in the accumulation of glycogen in the body and causing damage – particularly to muscle tissue. Enzyme replacement therapy is available for this condition that can dramatically attenuate, but not stop, disease progression. More effective treatments, such as gene therapy, are needed that can hopefully stop the disease from progressing.

AT845 is an adeno-associated virus 8 (AAV8) vector-based gene replacement therapy that delivers a functional copy of the GAA gene.

In the trial, participants (2 female, 2 male; mean age at dosing 54.5 years) received a one-time intravenous infusion of AT845 at either 3x1013 vg/kg or 6x1013 vg/kg dose (n=2 each). All participants showed evidence of AT845 vector transduction and an increase in GAA activity in the muscle compared to baseline.Three participants developed transient, steroid responsive transaminitis that was mild to moderate and deemed possibly related to AT845. One participant in the 6x1013 vg/kg cohort developed a peripheral sensory neuropathy that led to the US Food and Drug Administration (FDA) to place a hold on the clinical trial in February 2022. As noted by Dr. Diaz-Manera, data has been presented to the FDA showing the patient has improved and the clinical hold has been lifted.

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