A $957,000 grant will support research at the University at Buffalo into events that precede the onset of neurodegeneration in multiple sclerosis (MS). Specifically, the funding by the U.S. Army Medical Research and Development Command will be used to investigate possible changes in cell metabolism that lead to disease onset or progression in patients. “The project has the potential to impact MS clinical science and patient care,” Murali Ramanathan, the project leader and a professor at the university's School of Pharmacy and Pharmaceutical Sciences, said a press release. Metabolism describes the chemical reactions that occur in cells — metabolic pathways can provide energy for the cell, produce molecules that the cells need, and break down large molecules into smaller building blocks. Metabolic reactions are necessary for the proper functioning of a cell. The immune system and the nervous system have high metabolic demand — both are highly active and require considerable energy to work as they should. Things that disrupt metabolic pathways can cause permanent and irreversible damage to cells and nervous system tissue. The researchers plan to study metabolic changes in people with relapsing-remitting MS and progressive MS over five years, as well as changes in the levels of serum neurofilament light chain (sNfL), a protein released into the blood when nerve cells are damaged. Alterations in the brain's gray matter volume, the accumulation of brain MRI lesions, and other measures of disease progression and neurodegeneration will also be assessed. Ramanathan, working with colleagues, has previously shown that higher sNfL levels are associated with an increase in grey matter atrophy in the brains of MS patients. These researchers also found evidence suggesting that high sNfL levels during MS onset are associated with a significant loss of the blood-brain barrier (BBB) integrity and greater immune cell movement outside the circulatory system. The BBB protects the brain and limits the entry of immune system cells; a loss of BBB integrity allows for immune cells to enter areas of the brain where they can cause damage. They also reported links between apolipoproteins, high sNfL levels, and grey matter injury in people with MS, and between cholesterol and MS fatigue. (Apolipoproteins are molecules that bind to lipids or fats, transporting them in blood and cerebrospinal fluids.) According to the team, all these findings, together with discoveries that might come from the new project, could be important in understanding metabolism as it relates to MS. “Our findings can be leveraged for developing diet, lifestyle, and drug interventions for preventing progression and improving outcomes for MS patients,” Ramanathan said.