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Drug treatment for spinal muscular atrophy type I

  • Review
  • Intervention

Authors


Abstract

Background

Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells of the spinal cord, which leads to progressive muscle weakness. Children with SMA type I will never be able to sit without support and usually die by the age of two years. There are no known efficacious drug treatments that influence the course of the disease. This is an update of a review first published in 2009.

Objectives

To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA type I, and to assess if such therapy can be given safely. Drug treatment for SMA types II and III is the topic of a separate updated Cochrane review.

Search methods

We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to 8 March 2011). We searched the Clinical Trials Registry of the U.S. National Institute of Health (www.ClinicalTrials.gov) (8 March 2011) to identify additional trials that had not yet been published.

Selection criteria

We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA type I. Participants had to fulfil the clinical criteria and have a deletion or mutation of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis.

The primary outcome measure was time from birth until death or full time ventilation. Secondary outcome measures were development of rolling, sitting or standing within one year after the onset of treatment, and adverse events attributable to treatment during the trial period.

Data collection and analysis

Two authors (RW and AV) independently reviewed and extracted data from all potentially relevant trials. For included studies, pooled relative risks and standardised mean differences were to be calculated to assess treatment efficacy.

Main results

One small randomised controlled study comparing riluzole treatment to placebo for 10 SMA type 1 children was identified and included in the original review. No further trials were identified for the update in 2011. Regarding the primary outcome measure, three of seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months, whereas all three children in the placebo group died; but the difference was not statistically significant. Regarding the secondary outcome measures, none of the children in the riluzole or placebo group developed the ability to roll, sit or stand, and no adverse effects were observed. For several reasons the overall quality of the study was low, mainly because the study was too small to detect an effect and because of baseline differences. Follow-up of the 10 included children was complete.

Authors' conclusions

No drug treatment for SMA type I has been proven to have significant efficacy.

Plain language summary

Drug treatment for spinal muscular atrophy type I

Spinal muscular atrophy (SMA) is a severe neuromuscular disease with onset in childhood and adolescence that results in progressive muscle weakness. There are three main types of SMA. Drug treatment for SMA types II and III is discussed in a separate Cochrane review. The age of onset of SMA type I, also known as Werdnig-Hoffmann disease, is before six months. Children with SMA type I will never be able to sit without support and usually die by the age of two years. It is one of the most important causes of death due to a genetic disease in childhood. There was only one small randomised trial in the original review, which assessed the efficacy of riluzole for 10 children with SMA type I. In this trial all three children in the placebo group died, but three of the seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months. However, none of the children in the riluzole or placebo group developed the ability to roll, sit or stand. For several reasons the overall quality of the study was low, mainly because the study was too small to detect an effect and there were baseline differences that resulted in risk of bias. Evidence is insufficient to recommend riluzole for SMA type I. No further trials were identified for this 2011 update. No drug treatment has been shown to have significant efficacy for SMA type I.