Systematic Review of Presymptomatic Treatment for Spinal Muscular Atrophy

Area of Science:

• Neurology
• Genetics
• Pediatrics

Background:

• Spinal muscular atrophy (SMA) is a genetic disorder causing motor neuron degeneration.
• Approved treatments like nusinersen, risdiplam, and onasemnogene abeparvovec are effective but show greater benefit when initiated early.
• Emerging evidence suggests presymptomatic treatment yields superior outcomes.

Purpose of the Study:

• To systematically review prospective studies on presymptomatic treatment for 5q SMA.
• To evaluate the effectiveness of early intervention initiated before symptom onset.
• To compare outcomes of presymptomatic treatment versus symptomatic treatment.

Main Methods:

• Systematic review of prospective studies (interventional and observational) published up to December 2023.
• Inclusion of single-arm interventional studies (NURTURE, RAINBOWFISH, SPR1NT) and observational studies comparing cohorts.
• Analysis of follow-up data from screened cohorts identified via newborn screening.

Main Results:

• Babies with 3 SMN2 copies treated presymptomatically (nusinersen, onasemnogene abeparvovec) mostly achieved motor milestones.
• Babies with 2 SMN2 copies showed some delays and required support.
• Comparative studies indicated improved outcomes with presymptomatic treatment versus symptomatic treatment.

Conclusions:

• Presymptomatic treatment for SMA, particularly following newborn screening, appears to improve outcomes compared to later intervention.
• Further research is needed on long-term clinical outcomes and cost-effectiveness.
• Early diagnosis and intervention are crucial for managing SMA effectively.