RealTalk MS – Episode 444: Treating MS with a GLP-1 with Dr. Ellen Mowry

Release Date: March 2, 2026
Host: Jon Strum
Guest: Dr. Ellen Mowry (Principal Investigator, International Progressive MS Alliance clinical trial)

Episode Overview

In this episode, Jon Strum discusses groundbreaking research into how GLP-1 receptor agonists, commonly known by brand names like Ozempic and Mounjaro, might be repurposed to treat progressive Multiple Sclerosis (MS). The featured guest, Dr. Ellen Mowry, provides an in-depth look at a newly-launched clinical trial investigating whether a specific GLP-1 drug, NLY01, can protect neurons and reduce brain inflammation in people with progressive MS. The episode breaks down both the science and clinical trial approach, while also highlighting broader MS research news and the future of treatment paradigms.

Key Discussion Points & Insights

1. Proteomics Advances in MS Diagnosis and Monitoring (03:30–09:00)

• Definitions:

  • Proteome: The full set of proteins in an organism at a given time.
  • Proteomics: Study of the proteome, often through mass spectrometry.
  • Protein panel: A group of proteins used as a biomarker to detect or predict disease.

• Recent Discovery:
  Scientists at the Max Planck Institute identified a cerebrospinal fluid (CSF) protein panel that acts as a reliable biomarker for MS using advanced mass spectrometry.

  • This allows for more accurate diagnoses and early prediction of disease progression.
  • “...the biological information required to predict an individual's future MS disease course is already present at the time that individual is diagnosed. And that could be a game changer...” – Jon Strum (08:40)

2. International Progressive MS Alliance’s New Well-Being Research Initiatives (10:10–13:10)

• Overview: Three global studies, funded with over $8 million, target fatigue, cognitive impairment, pain, and mobility in progressive MS:

  • Pain Self-Management: Telehealth vs. coached vs. therapist-delivered pain management.
  • Brain Priming & Rehabilitation: Testing transcranial direct current stimulation and aerobic exercise before cognitive/mobility training.
  • Adaptive Exercise Program: Tailored interventions for walking capacity and fatigue.

• Notable Moment:
  “Participants in the study will include people with moderate to severe disability, which is an often overlooked group...” – Jon Strum (12:20)

3. Merck & Mayo Clinic Collaboration on Big Data & AI in MS Drug Discovery (13:00–13:20)

• Details:
  Collaboration leverages AI and big data, with focus areas including MS, to improve drug target identification.

4. Main Interview: GLP-1 Agonists as a Novel MS Therapy (13:22–29:46)

Background: Why Consider GLP-1s for MS? (13:25–16:22)

• Host Question: What was the “aha moment” for considering these drugs in progressive MS?
• Dr. Mowry’s Insight:
  • “...Outcomes generally are worse for people with MS who are living with these comorbidities [like diabetes, hypertension, obesity]...” (14:30)
  • Behavioral modifications show promise but are hard to sustain; GLP-1s are effective for these metabolic conditions.
  • Mouse model studies showed GLP-1s protect nerve cells from dying—a key factor in progression.

About NLY01: The Study Drug (16:22–17:53)

• What is NLY01?
  • A pegylated version of exenatide (GLP-1 agonist), provided by Neurali.
  • Pegylation makes it longer-lasting and enables it to cross the blood-brain barrier.
• Memorable Quote:
  “If it does work and it’s dependent on mechanisms directly in the brain, that’s pretty reassuring.” – Dr. Mowry (16:57)

Targeting Brain Inflammation & Neuroprotection (17:53–19:15)

• NLY01 reduces activation of astrocytes (support glial cells) to a toxic phenotype, reducing nerve cell death in the brain and retina.

• Quote:
  “In the mouse models, they saw that NLY01 reduced the activation of those astrocytes into the toxic phenotype and subsequently led to less nerve cell death in the retina.” – Dr. Mowry (18:40)

Shifting Focus: From Immunosuppression to Neuroprotection (19:15–21:20)

• Most MS drugs block the peripheral immune response; this trial aims at protecting nerve cells already under inflammatory stress in the brain.

• Quote:
  “We’re really all trying to figure out, how do we slow down that process? Because once enough nerve cells have died, people start to accumulate disability, and that is what we call progressive MS.” – Dr. Mowry (21:00)

Advanced MRI & Measuring Progression (21:20–23:01)

• Using new MRI modalities to observe:

  • Brain volume (main outcome)
  • Metabolic activity
  • Iron deposition
  • Diffusion techniques for nerve integrity

• Quote:
  “We’re looking at some special fancy MRI measures of, for example, metabolism in the brain... to help us better gain an understanding of what’s going on in MS progression...” – Dr. Mowry (21:44)

Trial Criteria & Study Design (23:01–24:42)

• Recruiting people stable from relapses or new MRI lesions—aiming to prevent, not treat, relapse triggers.

• MRI is primary outcome, as nerve cell loss can occur “under the surface” before clinical symptoms appear.

• Quote:
  “The idea, I think, should be for the field to identify people at risk of clinical progression where their symptoms are getting worse before that actually happens.” – Dr. Mowry (24:10)

Harnessing Metabolic Pathways in MS (24:42–26:11)

• GLP-1 trial represents a new chapter that uses metabolic intervention, not just behavioral modification.

• Quote:
  “It is using a new tool in the toolkit that appears to be more powerful than behavioral modification alone...” – Dr. Mowry (25:05)

What’s the Timeline for Real-World Impact? (26:11–29:32)

• If positive, further (Phase III) trials required for clinical approval.

• Current trial includes patients with BMI ≥27 due to regulatory and safety considerations.

• Quote:
  “We do need to do a much larger study, right, because you want to make sure that the results you’re finding with the MRI scans translate to a clinical benefit in terms of preventing real clinical disability worsening.” – Dr. Mowry (26:49)

Notable Quotes & Memorable Moments

• “The biological information required to predict an individual's future MS disease course is already present at the time that individual is diagnosed. And that could be a game changer...”
  — Jon Strum, 08:40

• “In the mouse models, they saw that NLY01 reduced the activation of those astrocytes into the toxic phenotype and subsequently led to less nerve cell death in the retina.”
  — Dr. Ellen Mowry, 18:40

• “We’re really all trying to figure out, how do we slow down that process? Because once enough nerve cells have died, people start to accumulate disability, and that is what we call progressive MS.”
  — Dr. Ellen Mowry, 21:00

• “I love the idea of identifying products that are already out there and saying like, wait, if there’s a rationale to try it, what are we waiting for?”
  — Dr. Ellen Mowry, 25:49

Timestamps for Key Segments

• 03:30 – Introduction to proteomics and new protein panel for MS diagnosis/prognosis
• 10:10 – Overview of new global well-being research studies for progressive MS
• 13:00 – Merck & Mayo Clinic AI/MS collaboration
• 13:22 – 29:46 – Deep dive interview with Dr. Ellen Mowry on the GLP-1 trial:
  • 13:25 – Why GLP-1s for MS?
  • 16:22 – What is NLY01?
  • 17:53 – Mechanism: glial cell modulation
  • 19:15 – Focus shift: neuroprotection
  • 21:20 – MRI and trial methodology
  • 23:01 – Participant criteria
  • 24:42 – New chapter in MS research
  • 26:11 – Roadmap for future approval

Episode Summary & Utility

This episode offers an accessible breakdown of the promise and mechanics behind repurposing GLP-1 agonist medications for progressive MS—a paradigm shift from immunosuppression to neuroprotection and metabolic intervention. Dr. Ellen Mowry’s interview is particularly insightful for patients, caregivers, and clinicians eager to understand both the “why” and “how” behind the current trial, its scientific rationale, and what could come next for the MS community.

Listeners come away with:

• An understanding of the new wave of MS biomarkers
• Details on exciting new global research into MS symptoms
• Context and specifics on the nation’s first GLP-1/progressive MS clinical trial
• A glimpse into the evolving landscape of MS treatment and drug development