P2.216: A comparison of SMA type 1 outcomes in two brothers treated with disease-modifying and gene therapies

Introduction: Spinal muscular atrophy (SMA) is a debilitating autosomal recessive condition most often caused by a mutation in the survival motor neuron gene 1 (SMN1) gene. It is characterized by the destruction of anterior horn cells, leading to progressive muscle atrophy with severity depending on the type of SMA. The disorder is classified into 5 different types based on the age of onset and highest motor function achieved. The most common form of SMA is type 1, also known as Werdnig-Hoffman disease, which has symptom onset prior to 6 months of age and is characterized by never achieving the ability to sit independently. Zolgensma (onasemnogene abeparvovec) is a single dose medication which delivers a functional copy of the SMN gene to motor neurons to improve functionality in patients with SMA. Other medications used in the treatment of SMA include Spinraza (nusinersen) and Evrysdi (risdiplam) which alter the splicing of the SMN2 gene in order to produce a full length SMN protein.

Case Description: Two brothers, both born with SMA 1, received Zolgensma gene therapy. Sibling A had a delay in diagnosis and received therapy at 123 days old. Sibling B was diagnosed in utero and received therapy at 35 days old. Both children were given Spinraza before Zolgensma. Following gene therapy, both children received physical therapy, occupational therapy, and speech therapy. Within a year of receiving Zolgensma, Risdiplam was started. Sibling A has had numerous hospitalizations, primarily due to respiratory complications. His primary feeding is through a PEG tube. He is mainly wheelchair bound and has severe scoliosis. At four years of age, he has achieved independent sitting, independent rolling, and head control with minimal assistance. Sibling B has had fewer hospitalizations and can orally feed most of his foods with only supplementation through a PEG tube. While he does have a wheelchair, at the age of 2 years and 10 months, he can independently sit, roll, crawl as well as stand with minimal assistance and walk with the aid of a gait trainer.

Discussion: The two children both have SMA type 1 with identical home environments and services provided, thus making this an interesting case to evaluate the sole variable of Zolgensma administration time on disease progression. In this case report, the child who received gene therapy earlier has met more developmental milestones and had fewer complications secondary to SMA.

Conclusion: This case demonstrates the importance of early administration of gene therapies such as Zolgensma to optimize developmental outcomes and prevent potential SMA-related complications. It also highlights the importance of early childhood screening for such diseases to allow for early pharmaceutical interventions.