On the other side, therapeutic use of rhIGF-I has been debated in ALS, since a Cochrane systematic evidence review found that the available randomized placebo controlled trials[335,336] did not permit a definitive assessment of its clinical efficacy[407], with just a small significant benefit in favor of recombinant IGF-I, which clinical relevance is unclear. Here, IGF1 is linked to amyotrophic lateral sclerosis.