Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis, also known as motor neuron disease

Amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) is a fatal neuromuscular disease characterized by progressive muscle weakness that results in paralysis. Ciliary neurotrophic factor (CNTF) has been shown to slow disease progression and improve muscle strength in an animal model of MND, through survival-promoting effects on motor neurons. Ciliary neurotrophic factor treatment did not show any significant effect on the progression of amyotrophic lateral sclerosis and side effects were observed at high concentrations.The review found only two eligible trials with a total of 1300 participants; the risk of bias was low for one trial but was unclear for the other trial; they did not show any significant effect of ciliary neurotrophic factor on progression of ALS or MND in man. On the other hand, several adverse effects were observed after treatment with ciliary neurotrophic factor. An updated search was performed in April 2011, but no new studies were found.

Authors' conclusions: 

Ciliary neurotrophic factor treatment had no significant 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.

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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. This is an updated review. An updated search was performed in April 2011, but no new studies were found.


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

Search strategy: 

We updated the searches of the Cochrane Neuromuscular Disease Group Specialized Register (19 April 2011), CENTRAL (2011, Issue 2), MEDLINE (January 1966 to April 2011) and EMBASE (January 1980 to April 2011), checked the reference lists of papers identified and contacted the authors of identified studies to get additional unpublished results.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.
We did not specify outcomes as selection criteria. In the review our outcome measures were as follows.
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: 

Three review authors independently checked all titles and abstracts from the searches to identify eligible randomized controlled trials. Two review authors independently extracted data and a third checked the data. We obtained some missing data from the investigators. Two authors independently assessed the risk of bias for each included study.

Main results: 

Two trials with a total population of 1300 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 risk of bias was low for one trial but was unclear for the other trial. No new trials were found on updating the search in April 2011. 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 risk ratio was 1.07 (95% confidence interval 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 ciliary neurotrophic factor.