Mitochondria and progressive MS

Project Summary:

Developing potential drug candidates that preserve and protect neurons in progressive MS is dependent on the early identification of disease (prodromal phase). This project aims to leverage existing models for insight into pathological mechanisms of tissue damage, including neurodegeneration, inflammation and energy failure through damage to mitochondria, as well as the cellular mechanisms underlying the clinical presentation of progressive MS, while identifying the prodromal phase of progressive MS through performance related and reversible symptoms, such as exercise induced fatigue (motor fatigability). These reversible symptoms are frequently reported by individuals affected by MS and they become gradually more prominent over time, before the diagnosis of progressive MS. Preliminary findings indicate a role for mitochondria and cellular energy failure in the worsening of these exercise induced symptoms over a period of time, reflecting the dysfunction of vulnerable neurons before degeneration. By identifying such dysfunction earlier, neurodegeneration can be delayed and resulting symptoms improved through therapeutic targeting of mitochondria. A model of earlier identification of progressive MS will provide a clinical platform enabling future clinical trials to be performed more efficiently.