Gene Therapy Among SMA Treatments Offering New Hope at Hackensack Meridian Children’s Health

Recent addition of SMA to newborn screening creates opportunities for early intervention in infants with spinal muscular atrophy

There are new rays of hope for advances in gene therapy treatments for Spinal Muscular Atrophy (SMA), usually inherited in an autosomal recessive pattern.

The availability of treatments that need to be instituted early and the frequency of SMA gave impetus for the addition of SMA to the newborn screening in New Jersey on January 31, 2022.

The disease is caused by a mutation in the Survival Motor Neuron 1 (SMN1) gene, most often a mutation on Exon 7, leading to an inability to produce SMN1 protein. However, the SMN2 gene, a defective SMN gene, produces only low levels of the SMN protein due to defective transcription, causing a progressive disease. The severity of the disease has been found to correlate with the number of SMN2 copies.

Newborns can experience a rapid onset of symptoms within the first 6 months of life. With the ability to screen newborns for SMA, we are now able to treat infants with SMA prior to the onset of symptoms. Presently, there are three available treatments for SMA.

In May 2019, the first gene transfer therapy was approved by the FDA for the treatment of SMA in children under two years of age. Hackensack Meridian Children’s Health was the first hospital network in New Jersey to perform this gene therapy in children. Onasemnogene abeparvovec (Zolgensma®) is a one-time infusion that delivers the SMN gene into patients' cells and allows for the continued production of the missing SMN1 protein. Initial trial data looking at presymptomatic infants with 2 or 3 copies of SMN2 treated at less than 6 weeks of age demonstrates the benefits of treating prior to symptom onset.

The first treatment for SMA, Nusinersen (Spinraza®), approved by the FDA in December 2016, is an antisense oligonucleotide (ASO) delivered intrathecally via lumbar puncture every 4 months, which increases the production of functional SMN2 protein. Initial trial data of presymptomatic infants with 2 or 3 copies of SMN2 who were treated at age 6 weeks and younger shows the benefits of early treatment.

Another treatment option, Risdiplam (Evrysdi®), an oral ASO taken daily, was initially approved by the FDA in August 2020, with expanded approval for infants younger than 2 months old in May 2022. The initial trial is still ongoing, however early data of presymptomatic infants with 2 or 3 copies of SMN2 treated before 40 days of age followed for one year shows benefits in achieving early motor milestones and lack of need for permanent respiratory support (data collection is still ongoing).

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