Proposed Study to Uncover Insulin Signaling's Role in ALS Motor Neuron Reinnervation and Muscle Function

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder, typically leading to death within 3-5 years due to respiratory failure. Current treatments like Riluzole offer only modest survival benefits without improving muscle strength. Initial motor neuron loss in ALS is compensated by collateral reinnervation, but this often fails, leading to progressive weakness. Maintaining this compensatory response is crucial for functional preservation and survival. While energy metabolism and glucose homeostasis influence ALS progression, the underlying mechanisms are unknown. Insulin signaling, which shares pathways with IGF-1 and regulates glucose and muscle mass, has not been investigated for its role in preserving muscle innervation and function in ALS.

This study proposes to investigate the critical role of insulin signaling pathways in maintaining collateral reinnervation and muscle function in ALS. Researchers aim to determine the specific contributions of these pathways to motor neuron preservation. Furthermore, the study will explore the link between insulin signaling and the disease-modifying effects of metabolic and glucose homeostasis perturbations. This involves identifying how distinct metabolic profiles influence the preservation of skeletal muscle innervation, providing insights into potential therapeutic avenues for ALS.