“We feel very fortunate to have the opportunity to be part of this exciting research and look forward to working with all of our participant volunteers,” says Ilana Katz Sand, MD
For those living with Multiple Sclerosis (MS), GLP-1 receptor agonists (GLP-1 RA) might represent a new mechanism for combating disease progression. Though initially developed for diabetes treatment, GLP-1 agents have become famous for inducing weight loss. However, the investigators behind the TAG-MS clinical trial, now recruiting patients at The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, are hopeful that GLP-1 RAs will demonstrate therapeutic benefits beyond their metabolic impact.
The study drug, NLY01, is a modified version of an existing GLP1-RA that has already been approved by the Food and Drug Administration for the treatment of type 2 diabetes. The modified drug exhibits a key difference: NLY01 maintains a significantly higher sustained concentration in the body and has other characteristics that enable it to more readily cross the blood-brain barrier. Given the widespread presence of GLP-1 receptors in the brain, this property led investigators to hypothesize that NLY01 may be able to directly target the central nervous system inflammation implicated in neurodegeneration.
This theory has a solid scientific foundation: In a mouse model of brain inflammation commonly used to study MS, investigators found that NLY01 administration had anti-inflammatory and neuroprotective properties. They proposed that by reducing peripheral and central inflammation, the neurodegeneration that is a hallmark of progressive MS can be slowed.
Researchers have also expanded beyond mouse models. In a previous study of patients with Parkinson’s disease, the study drug showed improved clinical outcomes compared to a placebo control. Additionally, in a recent trial in Alzheimer’s disease, a GLP-1 agent resulted in a slower reduction in brain volume.
At first glance, research in Parkinson’s disease and Alzheimer’s disease may seem far removed from MS. However, Ilana Katz Sand, MD, Associate Director of the MS Center and Associate Professor of Neurology, emphasizes that while Parkinson’s and Alzheimer’s are distinct diseases from MS, they do share common pathways with regard to neuroinflammation and neurodegeneration. “Recent research in these conditions strengthens our rationale for studying them in MS,” she says.
Building on this scientific rationale, Ellen Mowry, MD, of Johns Hopkins University designed a new phase 2 study, funded by the International Progressive MS Alliance, to investigate these mechanisms. At Mount Sinai, Dr. Katz Sand is the principal investigator behind the study.
The overall aim of the TAG-MS study is to investigate whether NLY01 can protect against neurodegeneration in people living with MS. The study is a randomized, placebo-controlled trial. Approximately 40 participants enrolled at Mount Sinai will self-administer weekly injections of either the study drug or a placebo over the course of two years.
“In a randomized controlled trial, a computer program assigns whether each participant receives the active drug or the placebo,” says Dr. Katz Sand. “The study team cannot choose the treatment assignment, and no one involved with the study will even know the assignment until the study concludes… to avoid introducing bias into the results. However, regardless of whether participants receive the study drug or the placebo, all participants will remain on their current MS disease-modifying therapy and also receive lifestyle behavioral therapy by trained nurses, as well as a free Fitbit.”
The primary goal of the study is to measure how much brain volume is retained over time. A “decrease in brain volume is part of normal aging, but we know that people who live with MS can have a slightly greater rate of decrease than those who don’t,” says Dr. Katz Sand. “This is somewhat correlated with worsening of MS-related disability over time. Disease-modifying therapies can help partially protect the brain, and we hope to find that NLY01 provides additional protection from brain volume loss.”
In addition to monitoring brain volume with three MRIs over the two-year study period, additional data will be collected through OCT scans, blood samples, clinical assessments and questionnaires, and Fitbit devices. While the primary goal of TAG-MS is to evaluate whether NLY01 can slow brain volume loss, these additional health measures may provide valuable insight into how the treatment affects disease progression more broadly.
With enrollment now underway at Mount Sinai, Dr. Katz Sand is enthusiastic about beginning this new study.
“Interventions that protect against neurodegeneration are critically needed to delay, prevent, and slow progression in MS,” she says. “TAG-MS approaches this important issue from a totally new angle. We feel very fortunate to have the opportunity to be part of this exciting research and look forward to working with all of our participant volunteers.”
If you’re wondering if you’re eligible, take a look at the table below to determine if you fit the study criteria. Please don’t hesitate to reach out to coordinators Diya Pandey (diya.pandey@mssm.edu) and Chelsea Seidel (chelsea.seidel@mssm.edu) if you have any questions.
By Chelsea Seidel and Diya Pandey, research coordinators at The Corinne Goldsmith Dickinson MS Center