Gene Therapy for Postnatally Diagnosed Spinal Muscular Atrophy 

Anisha Chandra Schwarz, MS, MD
Neuromuscular Child Neurology
Mary Bridge Children’s Hospital

Dr. Danielle Coleman of Pediatrics Northwest knew at the first appointment that something was amiss. At 3 days old, her newborn patient had diffuse hypotonia, weakness, and had no startle reflex. Dr. Coleman referred her urgently to child neurology at Mary Bridge Children’s Hospital, where we confirmed that the baby had spinal muscular atrophy type I, or SMA.

This is an autosomal recessive neuromuscular disorder, with 1/50 people in the United States being silent carriers and 1/10,000 babies per year affected. It is caused by lack of functioning SMN1, or the gene responsible for survival motor neuron 1. Without the functional protein, the child becomes progressively weak over time as motor neurons die.

Type 1 is the most common, more severe, and typically fatal without treatment, whereas type 4 presents in adulthood and does not alter lifespan. Testing for SMA is slated to be added to the newborn screen in Washington later this year, and will not distinguish type.

Breakthroughs in treatment for this otherwise fatal condition led to human gene therapy, currently available in two forms. One-time IV treatment (onasemnogene abeparvovec-xioi or Zolgensma) transfers the missing genetic material into cells directly, carried within the shell of a virus known as AAV9 which crosses the blood-brain barrier. For those who cannot receive this, ongoing intrathecal injections of the drug nusinersen (Spinraza) alters a similar gene, SMN2, to produce protein that functions like the missing one (SMN1). Children who received either of these in clinical trials thrived and achieved milestones impossible without treatment. Many expect a normal lifespan. The response is better when given earlier and to those who are stronger at baseline.

On February 24, Mary Bridge Children’s Hospital gave Zolgensma, the most definitive gene therapy available for SMA type I, to the youngest postnatally diagnosed baby ever to receive it worldwide. Dr. Coleman’s patient was 2 weeks old at the time of the infusion.

As for our patient, she is already moving more and we have high hopes for her future! We are thankful for Dr. Coleman and the multidisciplinary team of people who made gene therapy possible for this family.

With treatment available, all infants with diffuse low tone, absent or low reflexes, and weakness can be referred urgently for evaluation, as can any older child with normal cognitive development but motor delay, muscle weakness, gait abnormalities, and diminished reflexes.

Soon, pediatricians across the state may receive calls about positive newborn screens for SMA, which should also prompt urgent referral for genetic confirmation and treatment evaluation.