Sensory neuronopathy secondary to gene therapy with AT845 for Pompe disease

Pompe disease is a rare genetic neuromuscular condition produced by pathogenic variants in the GAA gene. In recent years gene therapy using AAV has been tested in clinical trials. Our aim is to describe a late onset Pompe disease patient who developed sensory neuronopathy after initiating gene therapy with AT845 in a clinical trial. We describe the clinical, electrophysiological and response to treatment features of a 49-year-old woman with Pompe disease who developed a sensory neuronopathy after receiving AT845, an investigational adeno-associated virus (AAV) gene replacement therapy designed to deliver a functional human acid alpha-glucosidase gene. The patient started with progressive sensory symptoms affecting distal regions of the four limbs associated with gait ataxia two months after receiving intravenous infusion of AT845. A pure sensory axonal neuropathy was documented through neurophysiological studies and therefore a sensory neuronopathy was considered. Complementary studies were all negative. Sensory symptoms gradually improved after treatment with intravenous methylprednisolone and oral prednisone, although symptoms have not completely resolved after one year. Injury to dorsal root ganglion neurons has been reported in animal models treated with gene therapy using recombinant AAV, but there are limited reports of AAV-mediated sensory neuronopathy in clinical trials. This case illustrates the need of careful review of neurological symptoms and clinical signs in patients treated systemically with AAV, and of repeated neurophysiological studies.