Current Advances and Challenges in Gene Therapies for Neurologic Disorders: A Review for the Clinician

Over 300 million people globally are affected by rare diseases, many of which present predominantly with neurologic symptoms. Rare neurologic disorders pose significant diagnostic and therapeutic challenges including delayed diagnoses, limited treatment options, and a shortage of specialists. However, advancements in diagnostics, particularly next-generation sequencing and expansion of newborn screening, have significantly shortened the time to diagnosis for many of these disorders. Concurrently, the past decade has witnessed exponential development of new treatments for rare neurologic diseases, with several approved gene therapies and more trials under way. A range of targeted therapies now offers hope for not only symptomatic management but also for disease modification. As treatments transition from clinical trials to clinical practice, the responsibility of identifying and monitoring patients may increasingly fall on the general neurologists. This evolving therapeutic landscape highlights the urgent need to enhance our understanding of this new class of medications and the details on clinical eligibility and monitoring of patients with diseases that have approved gene therapies. This article provides a comprehensive overview of gene-targeted therapies currently available for neurologic disorders, with a focus on their mechanisms, challenges, and post-treatment considerations.