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, 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 disease course.

Objectives

To evaluate if 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 type II and III will be will be the topic of a separate Cochrane review.

Search strategy

We searched the Cochrane Neuromuscular Disease Group Trials Register (September 30 2008, The Cochrane Library (Issue 3, 2008), MEDLINE (January 1966 to June 2008), EMBASE (January 1980 to June 2008), ISI (January 1988 to June 2008), and ACP Journal Club (January 1991 to June 2008).

Selection criteria

All randomized or quasi-randomized trials that examined the efficacy of drug treatment for SMA type 1 were sought. Participants had to fulfil clinical criteria and, in studies including genetic analysis to confirm the diagnosis, have a deletion or mutation of the SMN1 gene (5q11.2-13.2)

The primary outcome measure was to be time from birth until death or full time ventilation. Secondary outcome measures were to be 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 (WB and AV) independently reviewed and extracted data from all potentially relevant trials. For included studies pooled relative risks and pooled weighted standardized mean differences were to be calculated to assess treatment efficacy

Main results

One small randomized-controlled study comparing riluzole treatment to placebo for SMA type 1 was identified and included in the review. Regarding the primary outcome measure three of seven children treated with riluzole were still alive at the age 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 patients in the riluzole or placebo group developed the ability to roll, sit or stand, and no adverse effects were observed.

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 type II and III will be discussed in a separate Cochrane review. The age of onset of SMA type 1, 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 randomized trial on the efficacy of treatment with riluzole for patients with SMA type I. In this trial all three patients in the placebo group died, but three of the seven children treated with riluzole were still alive at the age of 30, 48 and 64 months. However, none of the patients in the riluzole or placebo group developed the ability to roll, sit or stand. Evidence is insufficient to recommend riluzole for SMA type I. No drug treatment has been shown to have significant efficacy for SMA type I.

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