Drug treatment for spinal muscular atrophy types II and III.

Renske I. Wadman, Wendy M J Bosboom, W. Ludo van der Pol, Leonard H. van den Berg, John H J Wokke, Susan T. Iannaccone, Alexander F J E Vrancken

Research output: Contribution to journalArticle

Abstract

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. This is an update of a review first published in 2009. To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA types II and III and to assess if such therapy can be given safely. Drug treatment for SMA type I is the topic of a separate updated Cochrane review. We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), Cochrane Central Register of Controlled Trials (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 March 8 2011). We also searched clinicaltrials.gov to identify as yet unpublished trials (8 March 2011). We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a deletion or mutation of the survival motor neuron 1 (SMN1) gene (5q11.2-13.2) that was confirmed by genetic analysis.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. Two authors independently reviewed and extracted data from all potentially relevant trials. Pooled relative risks and pooled standardised mean differences were to be calculated to assess treatment efficacy. Risk of bias was systematically analysed. Six randomised placebo-controlled trials on treatment for SMA types II and III were found and included in the review: the four in the original review and two trials added in this update. The treatments were creatine (55 participants), phenylbutyrate (107 participants), gabapentin (84 participants), thyrotropin releasing hormone (9 participants), hydroxyurea (57 participants), and combination therapy with valproate and acetyl-L-carnitine (61 participants). None of these studies were completely free of bias. All studies had adequate blinding, sequence generation and reports of primary outcomes.None of the included trials showed any statistically significant effects on the outcome measures in participants with SMA types II and III. One participant died due to suffocation in the hydroxyurea trial and one participant died in the creatine trial. No participants in any of the other four trials died or reached the state of full time ventilation. Serious side effects were infrequent. There is no proven efficacious drug treatment for SMA types II and III.

Original languageEnglish (US)
JournalCochrane database of systematic reviews (Online)
Volume4
StatePublished - 2012

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Spinal Muscular Atrophies of Childhood
Pharmaceutical Preparations
Therapeutics
Spinal Muscular Atrophy
Hydroxyurea
Creatine
Outcome Assessment (Health Care)
Life Expectancy
Ventilation
Phenylbutyrates
Acetylcarnitine
Anterior Horn Cells
Neuromuscular Diseases
Thyrotropin-Releasing Hormone
Sequence Deletion
Asphyxia
Muscle Weakness
Valproic Acid
Muscle Strength
Motor Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wadman, R. I., Bosboom, W. M. J., van der Pol, W. L., van den Berg, L. H., Wokke, J. H. J., Iannaccone, S. T., & Vrancken, A. F. J. E. (2012). Drug treatment for spinal muscular atrophy types II and III. Cochrane database of systematic reviews (Online), 4.

Drug treatment for spinal muscular atrophy types II and III. / Wadman, Renske I.; Bosboom, Wendy M J; van der Pol, W. Ludo; van den Berg, Leonard H.; Wokke, John H J; Iannaccone, Susan T.; Vrancken, Alexander F J E.

In: Cochrane database of systematic reviews (Online), Vol. 4, 2012.

Research output: Contribution to journalArticle

Wadman, RI, Bosboom, WMJ, van der Pol, WL, van den Berg, LH, Wokke, JHJ, Iannaccone, ST & Vrancken, AFJE 2012, 'Drug treatment for spinal muscular atrophy types II and III.', Cochrane database of systematic reviews (Online), vol. 4.
Wadman RI, Bosboom WMJ, van der Pol WL, van den Berg LH, Wokke JHJ, Iannaccone ST et al. Drug treatment for spinal muscular atrophy types II and III. Cochrane database of systematic reviews (Online). 2012;4.
Wadman, Renske I. ; Bosboom, Wendy M J ; van der Pol, W. Ludo ; van den Berg, Leonard H. ; Wokke, John H J ; Iannaccone, Susan T. ; Vrancken, Alexander F J E. / Drug treatment for spinal muscular atrophy types II and III. In: Cochrane database of systematic reviews (Online). 2012 ; Vol. 4.
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N2 - 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. This is an update of a review first published in 2009. To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA types II and III and to assess if such therapy can be given safely. Drug treatment for SMA type I is the topic of a separate updated Cochrane review. We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), Cochrane Central Register of Controlled Trials (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 March 8 2011). We also searched clinicaltrials.gov to identify as yet unpublished trials (8 March 2011). We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a deletion or mutation of the survival motor neuron 1 (SMN1) gene (5q11.2-13.2) that was confirmed by genetic analysis.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. Two authors independently reviewed and extracted data from all potentially relevant trials. Pooled relative risks and pooled standardised mean differences were to be calculated to assess treatment efficacy. Risk of bias was systematically analysed. Six randomised placebo-controlled trials on treatment for SMA types II and III were found and included in the review: the four in the original review and two trials added in this update. The treatments were creatine (55 participants), phenylbutyrate (107 participants), gabapentin (84 participants), thyrotropin releasing hormone (9 participants), hydroxyurea (57 participants), and combination therapy with valproate and acetyl-L-carnitine (61 participants). None of these studies were completely free of bias. All studies had adequate blinding, sequence generation and reports of primary outcomes.None of the included trials showed any statistically significant effects on the outcome measures in participants with SMA types II and III. One participant died due to suffocation in the hydroxyurea trial and one participant died in the creatine trial. No participants in any of the other four trials died or reached the state of full time ventilation. Serious side effects were infrequent. There is no proven efficacious drug treatment for SMA types II and III.

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