How is spinal muscle atrophy (SMA) treated?

Updated: Nov 05, 2018
  • Author: Ashish S Ranade, MBBS, MS, MRCS; Chief Editor: Jeffrey A Goldstein, MD  more...
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Curative therapy for SMA has been elusive. The survival rate is poor among young patients. Interest has arisen in the use of inhibitors of gamma-aminobutyric acid (GABA) synthesis, with promising results. Developments in the use of antisense-based therapy have been described. [29, 30]

In December 2016, the US Food and Drug Administration (FDA) approved nusinersen (Spinraza), the first drug approved for treatment of children (including newborns) and adults with SMA. Nusinersen is an antisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Through in-vitro assays and studies in transgenic animal models of SMA, nusinersen was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein. [31]

FDA approval was based on the ENDEAR trial, a phase 3 randomized, double-blind, sham-controlled study (N=121) in patients with infantile-onset (most likely to develop type 1) SMA. [32] At a planned interim analysis, the rate of achieving a motor milestone response was higher in infants treated with nusinersen (40%) than in those not so treated (0%), as measured by the Hammersmith Infant Neurological Examination (HINE). Additionally, a smaller percentage of patients died in the nusinersen group (23%) than in the untreated group (43%).

Interim findings from CHERISH, another phase 3 trial, involved 126 nonambulatory patients with later-onset SMA (consistent with type 2), including those with the onset of signs and symptoms at 6 months or later and an age of 2-12 years at screening. [33] Prespecified interim analysis demonstrated a difference of 5.9 points at 15 months between the treatment arm (n=84) and the sham-controlled arm (n=42), as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE). From baseline to 15 months of treatment, patients in the nusinersen group achieved a mean improvement of 4.0 points in the HFMSE, whereas those in the control group showed a mean decline of 1.9 points.


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