Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis or 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. It might be treated with ciliary neurotrophic factor.

Objectives

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

Search strategy

We searched the Cochrane Neuromuscular Disease Group Trials Register (searched to September 2006) for randomized trials, MEDLINE (from January 1966 to August 2006) and EMBASE (from January 1980 to August 2006); checked the reference lists of papers identified and contacted the authors of identified studies to get additional unpublished results.

Selection criteria

We considered the following selection criteria:
Types of studies: randomized controlled clinical trials.
Types of participants: 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 trial format.
Types of outcome measures:
Primary outcome: survival;
Secondary outcomes: 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).

Data collection and analysis

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

Main results

Two trials with a total population of 1,300 amyotrophic lateral sclerosis patients who were randomized to treatment with subcutaneous injections of recombinant human ciliary neurotrophic factor or placebo 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% confidence interval (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.

Authors' conclusions

Ciliary neurotrophic factor treatment has no effect on amyotrophic lateral sclerosis progression. At high concentrations, 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.