Researchers in France have trialed a new gene therapy approach to treat the central nervous system (CNS) aspect of the lysosomal storage disorder, Pompe disease. In an animal model, adeno-associated recombinant vector (AAV) mediated gene transfer was found to successfully correct cardiac and neurological regions affected by the inherited condition.
Current enzyme replacement treatment (ERT) for Pompe disease has managed to allay the inevitable fatality of the condition. However, the neurological phenotype and the persistence of selective muscular weakness in some patients requires further treatment as these may not be targeted by the ERT. Thus, a team from LUNAM Université tested an AAV mediated gene therapy to insert a corrected version of the mutated acid-α-glucosidase (GAA) gene, which results in glycogen storage.
Mice were used as the study’s subjects and the results found showed that there was functional neurologic correction in treated animals from 4 months onward, neuromuscular improvement from 9 months onward, and correction of the hypertrophic cardiomyopathy at 12 months. These changes were directly attributed to the CNS correction as muscle glycogen storage was not affected. Corrections on enzymatic, biochemical and histological levels were found in the cardiac and neurological areas most affected by the disease.
The research is published in the journal acta neuropathologica communications, and the team hope that ‘this unprecedented global and long-term CNS and cardiac cure offer(s) new perspectives for the management of patients.’
Source: Hordeaux J, et al., Long-term neurologic and cardiac correction by intrathecal gene therapy in Pompe disease. acta neuropathologica communications Sept 2017. DOI