IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

摘要: Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA caused by low levels survival motor neuron (SMN) protein that induce selective loss α-motor neurons (MNs) spinal cord, resulting progressive muscle consequent respiratory failure. To date, no effective treatment available to counteract course disease. Among different therapeutic strategies with potential clinical applications, evaluation trophic and/or protective agents able antagonize MNs degeneration represents attractive opportunity develop valid therapies. Here we investigated effects IPLEX (recombinant human insulinlike growth factor 1 (rhIGF-1) complexed recombinant IGF-1 binding 3 (rhIGFBP-3)) on a severe mouse model SMA. Interestingly, molecular biochemical analyses carried out mice before drug administration revealed marked reductions circulating hepatic mRNA expression. In this study, found perinatal IPLEX, even if does not influence body weight mice, results reduced MNs, increased fiber size amelioration functions mice. Additionally, show phenotypic changes observed are SMN-dependent, since significant SMN modification was addressed treated Collectively, our data indicate as good candidate hinder progression process