Neuromuscular disease - Gene transfer for children

Successful gene transfer therapy (GTT) provides a functional copy of a gene to appropriate tissues for affected patients. While technically difficult, GTT holds great promise for treating and even curing previously fatal diseases. GTT for Spinal Muscular Atrophy is available commercially and ongoing studies continue to show it is safe and effective. Subclinical liver dysfunction is more common in older, heavier children receiving higher vial loads. Human trials support preclinical studies showing early timing of therapy is important. GTT for Duchene Muscular Dystrophy has required strategic approaches to create mini- and micro-dystrophin genes that will fit into available viral vectors. There are multiple ongoing studies that overall demonstrate good safety and efficacy. GTT for X-Linked Myotubular Myopathy is being studied in an ongoing trial that has shown improvement in respiratory function (including ventilator independence), neuromuscular function, and histopathological evaluation. Three patients with severe cholestatic liver dysfunction have died. Evaluation is ongoing to better understand these events. While GTT for neuromuscular disorders holds significant promise, it is not without risks and requires in-depth knowledge of the disease, abundant pre-clinical work, careful patient education, and ongoing patient care. There are a number of key questions that must be considered regarding the feasibility of expanding GTT to new disorders These examples illustrate how advances in GTT benefit children on a population level and may themselves benefit from early detection by NBS. By becoming involved in advocacy at state and federal levels, families and physicians can impact newborn screening policy and implementation regarding these disorders.