Fast Five Quiz: Acute Infantile Spinal Muscular Atrophy Type 1, or Werdnig-Hoffmann Disease

Stephen L. Nelson, Jr, MD, PhD


August 12, 2020

Recent advances in the treatment of SMA have significantly altered prognosis even for patients with SMA type 1, the most severe form of the disease. Several innovative drugs have recently been approved that have been shown to improve symptoms and delay disease progression in many patients, particularly when they are administered before the onset of symptoms in addition to standard of care supportive therapies. Data from trials evaluating these agents highlight the importance of neonatal screening to expedite diagnosis and ensure early treatment to maximize outcomes.

Nusinersen is a disease-modifying antisense oligonucleotide directed at improving functional SMN protein expression by altering SMN2 transcript splicing. It was approved by the US Food and Drug Administration (FDA) in 2016 and by the European Medicines Agency (EMA) in 2017, making it the first drug approved for patients with SMA. Interim results from the NURTURE trial, a study to evaluate the safety and efficacy of nusinersen in presymptomatic patients, were overwhelmingly positive, with 100% of patients alive (median age at last visit, 26 months), 88% able to walk with assistance, and 77% of patients older than 18 months able to walk independently. Similarly, in the ENDEAR trial, 51% of patients treated with nusinersen achieved improvement in motor milestones, compared with none in the control group. In addition, whereas 75% of patients with disease duration ≤ 12 weeks responded positively, only 32% of those with a disease duration > 12 weeks did.

Onasemnogene abeparvovec-xioi, a recombinant AAV9-based gene replacement therapy that is designed to deliver a copy of the gene encoding the human SMN protein, was approved by the FDA in 2019 and the EMA in 2020. In the ongoing phase 3 STR1VE trial, all 15 patients receiving the gene therapy were alive and event-free at 20 months of age, compared with a survival rate of 8% in a historical cohort. Increases in motor function and significant milestone achievement were also seen in patients with SMA type 1 who received the gene therapy. The ongoing phase 3 SPR1NT trial is evaluating the safety and efficacy of onasemnogene abeparvovec-xioi administered to presymptomatic patients, with encouraging interim results reported thus far.

Learn more about treatment options for SMA type 1.


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