Current Roadblocks Toward Expanding Gene Therapy Across Pediatric Neurology: Shafali Jeste, MD

WATCH TIME: 6 minutes

"At the clinical trial stage, where we’re developing gene therapies and testing them, the conversations I have all the time in our field is that we need better biomarkers, better clinical end points to determine if a therapy is actually working. We need trial designs that are going to help us answer the question of whether these gene therapies work in a timely manner."

Pediatric neurological disorders are characterized with variable phenotypes, severity of symptoms, age at onset, and disease progression. Over the years, as genetic testing has advanced, gene-targeted therapies have become more of a reality for infants and children with these disorders. In 2019, the field broke through with the approval of Zolgensma (Novartis), the first approved gene therapy for infants with spinal muscular atrophy (SMA), the most severe form of SMA and a leading genetic cause of infant mortality. Years later, the FDA would approve SRP-9001, Sarepta's AAV vector-based gene therapy, as the first for patients with Duchenne muscular dystrophy, a neuromuscular condition that causes progressive weakness and loss of skeletal and heart muscles.

While the introduction of gene therapies has been exciting across walks of neurology, there are several challenges with their development and incorporation into clinical practice, says Shafali Jeste, MD. Jeste, chief of neurology and co-director of the Neurological Institute at the Children’s Hospital Los Angeles, was recently named the 2024 recipient of the prestigious Martha Bridge Denckla Award from the Child Neurology Society. Her lab, Kids with Neurogenetic and Developmental Disabilities (KiNDD), has defined early predictors of autism in at-risk infants, as well as biomarkers and clinical end points for trials in genetic neurodevelopmental disorders.

In a recent interview with NeurologyLive^®, Jeste spoke about the possibilities and promise of gene therapies in pediatric neurology, while noting the caveats that come with them. Specifically, she talked about the struggle to develop effective gene therapies and the ability to test them in timely manner. In addition, she spoke on the resources it takes to safely administer such agents and the financial burden for both parents and institutions. Furthermore, she touched upon the unknown aspects of gene therapy that still need resolving, such as long-term safety.