Shift Needed in Research, Treatment, for Aging MS Population

NASHVILLE, Tennessee — For the first time, the majority of patients with multiple sclerosis (MS) in the United States are, or soon will be, over age 55, a phenomenon that’s driving a shift in priorities including the creation of MS aging centers and a push for more clinical trials aimed at this growing patient population.

Given typical patterns of MS onset and its rate of progression, disease duration has long been thought to be the key variable driving disability, but Jennifer Graves, MD, PhD, director of the Neuroimmunology Research Program, University of California, San Diego, said she now believes that “patient age is actually more important.”

Speaking at a May 30 symposium at the Consortium of Multiple Sclerosis Centers (CMSC) 2024 Annual Meeting, Graves noted that it is well-known that key MS symptoms increase over time, particularly during the transition from a relapsing to a progressive phenotype.

However, she maintains that independent of disease progression, the impact of aging on MS has been underappreciated. She cited research showing that relative to chronological age, biologic age is more robustly correlated with MS outcomes.

In studies evaluating variables such as telomere length, various markers of senescence, and DNA methylation patterns, Graves and others have shown that biologic vs chronological aging is more rapid in patients with MS than those without the disease.

In addition, within the population with MS, there are also data supporting the premise that disease progression is slower in those with a younger vs older biologic age.

“This raises the question of whether biologic age is a driver of MS and whether we can slow the disease trajectory if we slow [biologic] aging,” Graves said. While she acknowledged that genetics play an important role in the aging process, she pointed to evidence showing exposure to toxins and other biological stressors, as well as poor lifestyle choices, such as lack of exercise and smoking, are modifiable aging variables.

There are already many avenues of research regarding aging processes and their interaction with MS. Graves spoke briefly about current research into the relationship between declining ovarian function, declining telomere length, and how this might relate to the transition to progressive MS and advancing disability. To date, her research has revealed a correlation between declining ovarian function and increasing MS disability.

The rapid aging of the population with MS in the United States makes research into slowing biologic aging a priority, said Robert Motl, PhD, professor in the Department of Physical Therapy, University of Alabama Birmingham Multiple Sclerosis Center. He reported he was able to secure funding from the National MS Society for the Healthy Aging through LifesTyle MS Research Center 10 years ago.

“We are the first and, so far, the only research center devoted to the study of aging in MS,” said Motl, another participant in the CMSC aging symposium. Motl said he and a colleague have been evaluating specific strategies to meet the varied needs of aging patients with MS with a key focus on physical therapy and preserving function.

Yinan Zhang, MD, an assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus, Ohio, recently started a multidisciplinary clinic for the management of older patients with MS and said he hopes these types of clinics will help shed light on the unmet needs of older adults with MS — particularly the need for better therapies to address common types of neurodegeneration in this population.

“We need to move away from immunomodulatory agents [in older patients],” Zhang said. Older patients, he added, are typically excluded from therapeutic MS trials for a number of reasons, not least because trials have been traditionally targeted at relapsing disease, which is less common in older patients with MS. He believes older patients are particularly appropriate candidates for MS therapy trials aimed at progressive neurodegeneration, which is characteristic of late-stage disease. Therapies with the potential to slow, or even reverse, demyelination are among the novel strategies being pursued in progressive MS.

Multidisciplinary Approach

Zhang acknowledged that his recently established MS clinic is still in the early phases and is largely focused on comprehensive care designed to meet the diverse needs of older individuals who often have advanced disabilities and comorbidities.

Currently, each patient that attends the clinic consults with six different types of providers, including a psychologist, a pharmacist, and a physical therapist — all in a single appointment.

Zhang said his decision to open a clinic was motivated by the increased volume of older patients with MS and was inspired by similar clinics for other disease states in older individuals.

“The need is already strong and growing,” said Zhang, who speculated that these types of clinics will become widespread as the need for this care is more broadly recognized and accepted.

As the clinic evolves and matures, Zhang anticipates there will be a research component to better characterize cell senescence and aging processes that might eventually be modifiable or even reversible. He also speculated that aging in MS might eventually become a subspecialty.

Graves reported financial relationships with Horizon Therapeutics. Zhang reported no potential conflicts of interest. Motl reported financial relationships with Bristol Myers Squibb.

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