Drug treatment for spinal muscular atrophy types II and III

Background Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. There are no known efficacious drug treatments that influence the disease course of SMA. Objectives To evaluate if drug treatment is able to slow or arrest the disease progression of SMA type II and III, and to assess if such therapy can be given safely. Drug treatment for SMA type I 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 We sought all randomized or quasi-randomized trials that examined the efficacy of drug treatment for SMA type II and III. Participants had to fulfil the 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 change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were to be change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full time ventilation, and adverse events attributable to treatment during the trial period. Data collection and analysis Two authors independently reviewed and extracted data from all potentially relevant trials. Pooled relative risks and pooled weighted standardized mean differences were to be calculated to assess treatment efficacy Main results Four randomized placebo-controlled trials on treatment for SMA type II and III were found and included in the review. The treatments were creatine, phenylbutyrate, gabapentin and thyrotropin releasing hormone. None of these trials showed any effect on the outcome measures in patients with SMA type II and III. None of the patients in any of the four trials died or reached the state of full time ventilation and serious side effects were infrequent. Authors' conclusions There is no proven efficacious drug treatment for SMA type II and III.