DAILY DIGEST

REPORTING FROM THE 2021
CONSORTIUM OF MULTIPLE SCLEROSIS CENTERS ANNUAL MEETING

THURSDAY, OCTOBER 28

On the Agenda Today

  • 8:00 am – 8:45 am: Donald Paty Lecture: Microbiome in Adults and Pediatrics, Emmanuelle Waubant, MD, PhD, Panzacola F/G
  • 9:00 am – 12:00 pm: Women in MS: Building Skills for Thriving In Your Career, Carrie Hersch, DO, Chair, Sandlake
  • 9:00 am – 12:00 pm: Late-Breaking Science, Corey Ford MD, PhD, Chair, Panzacola F/G
  • 12:00 pm: Meeting adjourned. See you in National Harbor, Maryland in June 2022!

Researcher Shares Promise and Perils of Lipoic Acid in Progressive MS

Amy Lovett-Racke, PhD (pictured), chaired Wednesday’s Whitaker Invited Lecture session consisting of reports from established MS researchers. Among the research updates was an update on the therapeutic potential of lipoic acid in progressive MS. Dr. Spain delivered her lecture remotely via the video platform.ORLANDO, Fla. – Lipoic acid is a naturally occurring antioxidant derived from food sources or supplements. Because oxidative stress is thought to be involved in the pathogenesis of multiple sclerosis (MS), antioxidants may have some neuroprotective or restorative properties. At the CMSC’s Whitaker Invited Lecture session here on Wednesday, Rebecca Spain, MD, MSPH, Associate Professor of Neurology at Oregon Health & Science University, reviewed her pilot study results and in-progress multicenter study of lipoic acid in patients with progressive multiple sclerosis (PMS).

Oxidative stress is an intriguing target for intervention in MS. Oxidative stress occurs when the oxidation from free radicals outweighs our normal cellular and nutritional antioxidant defenses. “The brain is particularly susceptible to oxidative stress,” Dr. Spain said. “While it only represents 2% of our body mass, it uses about 20% of our metabolic rate and consumes 20% more oxygen.” Oxidative stress has been shown to be present in animal models of MS and in studies of MS lesions.

“Lipoic acid falls into the category of nonenzymatic antioxidants. It is endogenous in that we synthesize it naturally in our bodies, but it can be taken as a supplement,” she told the audience. Lipoic acid is being studied in many other disease states, including metabolic syndrome and diabetes because of its functions as an insulin mimetic.

“Progressive disease that is no longer showing signs of inflammatory activity is exactly where we are lacking treatment,” Dr. Spain said. In her phase 2 pilot study of 31 patients with SPMS, 27 received lipoic acid and 24 placebo. The treated group showed a significant reduction in the primary outcome, whole brain atrophy, over the two-year study period. The most common adverse event was gastrointestinal upset, which can be mitigated by taking the supplement with food.

This “promise” of lipoic acid set the stage for Dr. Spain to launch a larger multicenter trial with the goal of enrolling 118 patients at 11 study sites. The trial is sponsored by the Veteran’s Administration and the National MS Society. However, an unexpected safety signal emerged that caused the larger trial to halt temporarily. Three cases of elevated proteinuria leading to a complication of membranous nephropathy occurred in the treated group and resolved after discontinuation of lipoic acid. In consultation with nephrologists and the safety review board, Dr. Spain’s study team instituted steps for screening and monitoring in order to proceed safely with the study of lipoic acid.

Because walking speed was a primary endpoint, the larger trial was unable to enroll patients with EDSS beyond 6.5, although Dr. Spain acknowledged the importance of research into treatments that will benefit patients with more advanced disability. Results from the multicenter trial are anticipated in about two years.

 

To register for the Annual Meeting educational sessions, please go to:

https://cmscscholar.org

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