Treatment with the growth factor, recombinant human insulin-like growth factor I, for amyotrophic lateral sclerosis (motor neuron disease)

Mitchell JD, Wokke JHJ, Borasio GD

Published Online:

October 5, 2011

Recombinant human insulin-like growth factor is a genetically engineered human protein. Theoretically, it is expected to enhance the survival of motor neurons which degenerate in amyotrophic lateral sclerosis also known as motor neuron disease. It is given by daily subcutaneous injection. Two randomised controlled trials involving altogether 449 participants measured disease progression on a special clinical rating scale of disease severity in amyotrophic lateral sclerosis. The combined results showed a small significant benefit in favour of rhIGF-I, the clinical relevance of which is unclear at present. Safety was not a major concern. The trials may have been too small and, in retrospect, inadequate in quality. Consequently, further trials are need to determine the effectiveness of insulin-like growth factor I for amyotrophic lateral sclerosis.

Abstract (click to read)

Background:

Trophic factors, including recombinant human insulin-like growth factor I (rhIGF-I) are possible disease modifying therapies for amyotrophic lateral sclerosis.

Objectives:

To examine the efficacy of recombinant human insulin-like growth factor I in amyotrophic lateral sclerosis.

Search strategy:

We searched the Cochrane Neuromuscular Disease Group Trials Register (March 2006), MEDLINE (January 1966 to March 2006) and EMBASE (January 1980 to March 2006) and asked the authors of randomised clinical trials and manufacturers of recombinant human insulin-like growth factor I.

Selection criteria:

We considered all randomised controlled clinical trials involving rhIGF-I treatment of amyotrophic lateral sclerosis in adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events.

Data collection and analysis:

We identified three randomised clinical trials. Only two were included in the analysis. Each author graded the studies for methodological quality. Data were extracted and entered by the lead author and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs.

Main results:

In a European trial with 59 participants on placebo and 124 on rhIGF-I, 0.1 mg/kg/day the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08), non-significantly less in the treated than the placebo group. In a North American trial, in which 90 participants on placebo were compared with 89 on recombinant human insulin-like growth factor I 0.05 mg/kg/day, and 87 participants on 0.1 mg/kg/day, the MD after nine months was -6.00 (95%CI -10.99 to -1.01), significantly less on treatment. The combined analysis from both randomised clinical trials showed a weighted mean difference after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. Similarly the data with the 0.05 mg/kg/day dose showed trends favouring rhIGF-I at all time points but did not reach significance at the five per cent level at any point. There was an increased risk of injection site reactions with rhIGF-I (relative risk 2.53, 95% CI 1.40 to 4.59).

Authors' conclusions:

The available randomised placebo controlled trials do not permit a definitive assessment of the clinical efficacy of rhIGF-I on ALS. More research is needed and one trial is in progress. Future trials should include survival as an outcome measure.

This record should be cited as:

Mitchell JD, Wokke JHJ, Borasio GD. Recombinant human insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD002064. DOI: 10.1002/14651858.CD002064.pub2

Assessed as up to date:

August 21, 2007

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Primary Review Group:

Neuromuscular Disease Group

Health topics:

Neurology > Motor neurone disorders > Amyotrophic lateral sclerosis/motor neurone disease

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Treatment with the growth factor, recombinant human insulin-like growth factor I, for amyotrophic lateral sclerosis (motor neuron disease)

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