THE INSULIN-LIKE GROWTH-FACTOR SIGNALING SYSTEM AND ALS NEUROTROPHIC FACTOR TREATMENT STRATEGIES

Because of its multi-faceted potential as a neurotrophic factor, insul in-like growth factor I (IGF-I) has been given to hundreds of ALS pati ents world-wide. Unlike some patients with post-polio syndrome and fra gile elderly males, it is unclear whether any of these patients posses s disturbances in IGF signaling. We found that about 25% of ALS patien ts in a controlled trial of human growth hormone (hGH) had lower or hi gher than normal IGF-I serum levels. Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way. In addition, in type I diabetes significant increa se in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complica tions are prominent. We have studied the response of IGFBPs in ALS pat ients to subcutaneous rhIGF-I and found transient induction of IGFBP-1 . Studies related to the IGFBPs have not been done in familial ALS (FA LS) patients. However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2. IGF-I has been given to several models of motor neuron degeneration in the mouse, inc luding motor neuron disease and wobbler, with beneficial effects. Howe ver, it is also not known whether any accepted genetic mouse model of motor neuron degeneration possesses any disturbance in the IGF signali ng system.