Cause of Multiple Sclerosis Progression Studied

The two-year project, headed by Murali Ramanathan, PhD, tests the hypothesis that nicotine metabolism, the byproducts of vitamin D metabolism and increased levels of anti-Epstein-Barr virus (EBV) each interact with variations in specific genes to cause increased neurodegeneration and increased lesions in MS patients.

Ramanathan is a professor of pharmaceutical sciences and neurology in the School of Pharmacy and Pharmaceutical Sciences and the School of Medicine and Biomedical Sciences, respectively.

The study is a collaboration between the UB and investigators from Charles University in Prague, Czech Republic, and will be conducted on samples obtained at both universities’ MS centers.

The research aims to identify gene-environmental interactions between key molecules in the vitamin D pathway, anti-Epstein-Barr virus antibodies, cigarette smoking and genetic variants that are implicated in conversion of patients with clinically isolated syndrome (CIS) to definite MS.

They will assess the risk of developing clinically definite MS and the time to progression, as well as the neurodegeneration in the brain of MS patients, as measured by brain atrophy, and the extent of brain injury caused by lesions.
 
“We will use a novel approach to measure the levels of vitamin D and its metabolites, EBV exposure and nicotine metabolites from cigarette smoking,” says Ramanathan. “We have developed sensitive and selective measurements for key metabolites in the vitamin D and nicotine metabolism pathways using mass spectrometry, a method that has not been used previously to study vitamin D metabolism.

The novel study design will include the genetic variations that were associated with the risk of developing MS, as well as genes that determine the levels and responses to environmental factors. MS patients will be divided into two equal groups: a training group that will be used to identify gene-environmental interactions, and a group that will be used to replicate the training group result.

“Identifying gene-environmental interactions is critical for developing better strategies for slowing the progression of MS, because it could enable patients with preexisting genetic risk factors to reduce the rate of disease progression through lifestyle modification,” Ramanathan says.

The study results will identify the gene-environment interactions that promote disease progression in MS and facilitate the development of preventive and therapeutic interventions for MS that disrupt these interactions, notes Ramanathan.

UB co-principal investigators include:

• Bianca Weinstock-Guttman, MD
• Robert Zivadinov, MD, PhD
• Jun Qu, PhD

Dana Horakova, MD, PhD, and Eva Havrdova, MD, PhD, are collaborators at Charles University in Prague.