Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold?

摘要: Abstract Since their discovery in the 1950s, neurotrophic factors have raised expectations that clinical application to neurodegenerative diseases might provide an effective therapy for what are now untreatable conditions. Nerve growth factor (NGF) was first be discovered and one of earliest proceed trials. NGF, which is selectively trophic small fiber sensory sympathetic neurons, selected as a potential diabetic polyneuropathy because serious consequences associated with degeneration those neuronal populations this condition. In addition, evidence shows reduced availability NGF may contribute pathogenesis neuropathy, animal models neuropathy respond exogenous administration NGF. Two sets phase II trials suggested recombinant human (rhNGF) at ameliorating symptoms both HIV related neuropathy. These early studies, however, revealed painful side effects were dose limiting A large-scale III trial 1019 patients randomized receive either rhNGF or placebo 48 weeks failed confirm earlier indications efficacy. Among explanations offered discrepancy between two robust effect, inadequate dosage, different study populations, changes formation trial. As result outcome, Genentech has decided no further development rhNGF.