The Untapped Promise of Genetics in Multiple Sclerosis

Two patients with multiple sclerosis (MS) can present almost identically and yet go on to have very different disease courses and responses to treatment. That reality sits at the center of the push toward precision medicine in MS, which aims to tailor care to the biology and circumstances of each individual rather than to broad disease categories. Progress in biomarkers, imaging, and immunology is bringing that goal closer. Translating those advances into everyday decisions, however, remains a work in progress.

NeurologyLive^®’s Roundtable series Precision Medicine in Multiple Sclerosis: Advances & Unanswered Questions, produced in collaboration with Cleveland Clinic Neurological Institute, examines where that work stands. Leading the conversation are Robert Bermel, MD, director of Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research; Marisa McGinley, DO, staff neurologist at the Mellen Center; and Rebecca Cebull, CNP, certified nurse practitioner at the Mellen Center. Together, they offer a candid, clinic-level view of the tools available today and the gaps that remain.

In episode 4, the panel turns to genetics and pharmacogenomics. McGinley admits that outside of label-required steps such as CYP2C9 genotyping before starting siponimod, pharmacogenetic data play little role in her daily practice. Cebull recalls a recent patient with a less common CYP2C9 variant that sent her team to the pharmacy and the manufacturer to sort out dosing. She notes that the experience underscored the need for genetically diverse clinical trial populations.

Bermel argues that the future likely lies not in a single gene but in multidimensional biological profiling that could predict disease course and guide treatment choices, such as whether a patient is better suited to a B-cell–depleting therapy or a Bruton tyrosine kinase inhibitor. He contrasts MS, which is still classified by observed phenotype, with oncology, where a term like “triple-negative breast cancer” immediately conveys biology and prognosis. Cebull adds that patients often ask about their children’s risk, and reliable genetic predictors could one day help answer those questions.