Treatment of SMA in a Preterm Infant with Elevated Anti-AAV9 Antibody Titers: A Case Report
Azalea Lee1, Sumit Verma2
1Emory University School of Medicine, 2Child Neurology, Emory University School of Medicine; Children's Healthcare of Atlanta
Objective:
To present a case of the treatment of a preterm infant with spinal muscular atrophy (SMA) using risdiplam bridging to onasemnogene abeparvovec (Zolgensma)
Background:
SMA type 1 is the most common monogenic cause of death in infancy. Standard gene therapy for SMA (onasemnogene abeparvovec or Zolgensma) is approved in the U.S. for infants younger than 2 years, but not until reaching full-term. Early administration has been linked to improved outcomes, yet limited data exist on its use in premature infants. Recent studies have explored in utero treatment with risdiplam, raising questions about prenatal versus postnatal initiation of therapy.
Results:
A dichorionic-diamniotic twin girl was born at 31 weeks 4 days, of whose newborn screen and genetic testing confirmed SMA with two SMN2 copies. Due to her prematurity and an elevated anti-AAV9 antibody titer (1:100), gene therapy could not be administered. Risdiplam was initiated at 34 weeks postmenstrual age. Baseline nerve conduction studies (NCS) at 33 weeks showed reduced compound muscle action potentials (CMAP) with normal distal latencies. CMAP normalized by 2 months corrected age (CA). The anti-AAV9 titer decreased to <1:25 by 2 months CA, and Zolgensma was administered at 3 months CA. CHOP-INTEND scores remained stable (52 at 38 weeks CA and 53 at 3 months, pre- and shortly post-gene therapy). However, NCS again showed CMAP reduction post-gene therapy. Muscle ultrasound also showed fasciculations, increased echogenicity, and decreased bulk. Risdiplam was continued after gene therapy. Intrathecal nusinersen is under consideration.
Conclusions:
Management of SMA in premature infants is complex, with no standardized approach. This case highlights the challenges of timing therapy and the potential discordance between clinical scales and neurophysiological measures early after therapy. Further research comparing in utero treatment with early postnatal therapy is crucial to determine optimal strategies for improving outcomes in preterm infants with SMA.
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