Gene therapy for childhood neuromuscular and neurodegenerative disorders: An update

The central nervous system is a rather complex site for gene therapy as it contains neurons, astrocytes, and oligodendrocytes, and they have discrete and intricate interconnections between them, establishing a delicate balance. However, with significant advances in scientific technology and development of new viral vectors, now, gene therapy has a greater promise for pediatric neurological disorders, especially for certain neurodegenerative diseases, which still remains to be invincible by other pharmacological modalities. Adeno-associated virus (AAV) vector is the predominant vector used for gene therapy currently. Gene editing therapy using antisense oligonucleotides has been successfully implemented in neuromuscular diseases such as dystrophinopathy and spinal muscular atrophy (SMA). Recently, an AAV-mediated gene therapy is approved by the Food and Drug Administration for SMA, and it is considered to be the most expensive drug in the world. Gene therapy for dystrophinopathy has also been safely tried in two clinical studies, although its efficacy is yet to be demonstrated. In Xlinked adrenoleukodystrophy, late infantile metachromatic leukodystrophy, late infantile neuronal ceroid lipofuscinosis and Canavan disease results of human trials are very much promising. Ongoing clinical trials in several lysosomal storage disorders such as mucopolysaccharidosis type III, Fabry disease, and Pompeii disease are currently active. In mouse models, several other neurodevelopmental disorders have also been tested successfully for gene therapy.