Grant: Proof of Principle Program Phase I - Drug Development

Amyotrophic lateral sclerosis (ALS) , also known as Lou Gehrig's disease, is a fatal neuromuscular condition that currently affects approximately 30,000 people in North America. In ALS, deterioration of upper and lower motor neurons causes gradual muscle paralysis and atrophy, affecting mobility, speech, swallowing and eventually respiration. Half of affected individuals are dead within 3 years, with less than 20% surviving for more than 5 years. There is a strong connection with inflammation in the brain possibly triggered through activation of specialized defence cells termed microglia. Indeed there is evidence of microglial activation in human postmortem brain and spinal cord tissue, and PET scanning of the brain of ALS patients strongly suggests a role for inflammatory cascades in ALS pathology. Thus excessive inflammation in the brain through microglia activation likely contributes to motor neuron dysfunction, injury and loss, and hence, to disease progression. We are proposing here to further develop an exciting new drug from the innate defence regulator peptide family, which has demonstrated efficacy in suppressing inflammation in a broad range of inflammatory situations including an animal model of severe ALS. Here we will determine whether specific formulations enhance effectiveness and also determine the optimal dosing schedule and amount.