Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/motor neuron disease.
BACKGROUND
Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neuromuscular disease characterized by progressive muscle weakness resulting in paralysis, which might be treated with ciliary neurotrophic factor.


OBJECTIVE
The objective of this review was to examine the efficacy of ciliary neutrophic factor in amyotrophic lateral sclerosis.


METHODS
We searched the Cochrane Neuromuscular Disease Group trials register (searched June 2003) for randomized trials, MEDLINE (from January 1966 to October 2003) and EMBASE (from January 1980 to October 2003), checked the reference lists of papers identified and contacted the authors of studies identified to get additional unpublished results.


METHODS
We considered the following selection criteria: Types of studies: randomized controlled clinical trials;


METHODS
adults with a diagnosis of either probable or definite amyotrophic lateral sclerosis according to the El Escorial criteria; Types of interventions: treatment with ciliary neurotrophic factor for at least six months, in a placebo-controlled randomized format; Types of outcome measures Primary: survival; Secondary: muscle strength, respiratory function, changes in bulbar functions, changes in quality of life, proportion of patients with adverse side effects (such as cough, asthenia, nausea, anorexia, weight loss and increased salivation).


METHODS
We identified two randomized trials. The data were extracted and examined independently by the reviewers. Some missing data were obtained from investigators.


RESULTS
Two trials, with a total population of 1,300 amyotrophic lateral sclerosis patients treated with subcutaneous injections of recombinant human ciliary neurotrophic factor, were examined in this review. The methodological quality of these trials was considered adequate. No significant difference was observed between ciliary neurotrophic factor and placebo groups for survival, the primary outcome measure. The relative risk was 1.07 (95% CI 0.81 to 1.41). No significant differences between the groups were observed for most of the secondary outcomes. However, a significant increase of the incidence of several adverse events was noted in groups treated with higher doses of CNTF.


CONCLUSIONS
Ciliary neurotrophic factor treatment has no effect on amyotrophic lateral sclerosis progression. At high concentration, several side effects were observed. A combination of ciliary neurotrophic factor with other neurotrophic factors (as suggested by results on animal models), and more efficient delivery methods should be tested.
Bongioanni
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Department of Neuroscience, University of Pisa, Via Paradisa, 2, Pisa, Italy, 56100. paolo.bongioanni@tin.it
Reali
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Sogos
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D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D020934:Ciliary Neurotrophic Factor / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D016472:Motor Neuron Disease / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
D020934:Ciliary Neurotrophic Factor