Feb 17 - The Horizon of Prenatal Therapies for Genetic Disorders OnDemand-Presentation

Video Transcription

Video Summary

The 2026 ACMG Education Webinar focused on innovative prenatal therapies for genetic disorders, featuring presentations by Billie Young-Glue and Dr. Richard Finkel. Billie Young-Glue discussed the PERL trial at UCSF, which is pioneering in utero enzyme replacement therapy (ERT) for fetuses with lysosomal storage disorders (LSDs), such as multiple mucopolysaccharidoses and Pompe disease. She highlighted the advantages of prenatal intervention, including earlier access to the central nervous system before the blood-brain barrier closes, immune tolerance to therapies reducing anti-drug antibody formation, and lower dosing with potential cost benefits. Early results from the trial showed promising outcomes, with mitigation of expected organ damage, absence of anti-drug antibodies, and normal development in treated infants. Challenges include multiple in utero procedures and limited CNS delivery postnatally. Future directions include prenatal gene therapies and genome editing.<br /><br />Dr. Richard Finkel presented on prenatal therapy for spinal muscular atrophy (SMA) using oral administration of the small molecule drug risdiplam to pregnant mothers, enabling fetal exposure through the placenta. SMA, caused by mutations in the SMN1 gene, presents severe motor neuron degeneration often starting in utero. Postnatal treatments exist, but prenatal intervention aims to prevent early neurodegeneration. Early cases (about 10 treated worldwide) have demonstrated feasibility and safety, with favorable biomarker trends and normal infant development, though longer-term efficacy remains under study. Challenges include proper dosing, monitoring fetal safety, and the need for structured clinical trials to optimize treatment protocols. Both speakers emphasized multidisciplinary collaboration, ethical considerations, and the importance of registries to assess long-term outcomes. They noted barriers to access, including high therapy costs, and stressed ongoing research to refine and expand prenatal genetic therapies.

Keywords

prenatal therapies

genetic disorders

enzyme replacement therapy

lysosomal storage disorders

multiple mucopolysaccharidoses

Pompe disease

spinal muscular atrophy

risdiplam

in utero treatment

prenatal gene therapy