RealTalk MS – Episode 436

Title: 3 Questions Your Neurologist Should Be Asking Themselves with Dr. Leorah Freeman
Host: Jon Strum
Guest: Dr. Leorah Freeman, Director of the Multiple Sclerosis and Neuroimmunology Center at Dell Medical School, UT Austin
Date: January 5, 2026

Episode Overview

This episode kicks off 2026 with a deep dive into the current and future landscape of multiple sclerosis (MS) treatment, particularly focusing on the emerging era of BTK inhibitors—an innovative class of MS drugs. Host Jon Strum is joined by Dr. Leorah Freeman, who explores the crucial questions neurologists must consider as new therapies, technologies, and approaches reshape MS care. The episode weaves news updates, patient-centered perspectives, and cutting-edge scientific discussion into an engaging and accessible conversation.

Key Discussion Points & Insights

Recent MS News & Updates

• USPS Postmark Changes Impacting Health Care (02:00-04:40)

  • New rules mean postmarks now reflect the date processed at an automated hub, which can be days after mailing. Jon urges listeners to plan ahead for critical healthcare documents, noting the potential impact on insurance, disability applications, and more.
  • “Planning ahead is usually a sound strategy for almost anything. In this case, it can make the difference in your ability to access health care without having to jump through a bunch of additional hoops.” – Jon Strum [04:13]

• FDA Rejection of Tolebrutinib for SPMS (04:45-08:45)

  • The FDA declined approval of Sanofi's tolebrutinib for non-active secondary progressive MS (SPMS), a move that surprised many given prior feedback and the drug’s “breakthrough” status.
  • BTK inhibitors (like tolebrutinib) represent a new class targeting both peripheral and central immune responses in MS.
  • Notable quote: "Today's FDA decision is a significant and meaningful change in direction... we remain committed to working with the FDA to find a path forward for tolebrutinib and ultimately serve the MS community." – Dr. Human Ashrafian, Sanofi [06:30]

• Biologically Informed MS Subtypes Identified (08:46-12:10)

  • AI-driven analysis of MRIs and blood biomarkers reveals two new MS subtypes (early SNFL and late SNFL) based on neurofilament light chain levels and types of brain damage.
  • Could lead to more precise, biologically targeted treatments rather than just symptom-driven MS course descriptions.
  • Jon emphasizes: “The more specifically those biological mechanisms can be described, the more targeted that individual’s treatment plan can be. And that’s the ultimate goal here.” [11:37]

• Study on Fear of Relapse/Progression in MS (12:11-15:32)

  • A systematic review of over 3,000 people with MS worldwide reveals fear of disease progression is common and closely linked to poorer mental health and quality of life.
  • Jon underscores the importance of evidence-based information and the power of education in managing uncertainty.
  • “Living with the uncertainty of MS is the worst part... That uncertainty can drive your imagination. And there’s no end to the ways our imaginations can create terrifying scenarios.” – Jon Strum [14:09]

• Experimental Medicine Trials for Progressive MS (15:33-17:17)

  • Two new clinical trials announced:
    • Hydroxychloroquine Trial (Finland) – Testing neuroinflammation reduction.
    • GLP-1 Agonists Trial (US/Johns Hopkins) – Testing neuroprotection and inflammation reduction.
  • Both trials emphasize patient involvement in their design.

Main Interview: Dr. Leorah Freeman on Neurology’s 3 Big Questions

Introduction to BTK Inhibitors (17:39-19:42)

• Dr. Freeman explains BTK inhibitors:
  • “BTK inhibitors are this new class of medication... They are able to get into the brain and modulate immune cells that reside within the brain—those resident B cells or the famous microglial cells thought to contribute to progressive disease.” – Dr. Freeman [18:21]
  • Current MS drugs mostly target peripheral inflammation, but BTK inhibitors might also address progressive MS by acting within the CNS.

Real-World Experience vs. Clinical Trials (19:42-22:05)

• Cautionary tales from past MS drugs:
  • Tysabri (natalizumab): Serious but rare brain infection (PML) discovered only after broad use, prompting new safeguards.
  • Gilenya (fingolimod): Early post-approval discovery of heart risks, requiring new monitoring protocols.
  • Importance of post-marketing vigilance: “We discover after the medication was approved... very serious complications... So that was really probably the most significant example.” – Dr. Freeman [20:11]

The Art and Science of MS Care (22:05-23:48)

• On “pairing innovation with vigilance, optimism with responsibility:”
  • “We have to really navigate very specific and individualized decisions with our patients, but we have to really be mindful that our decisions have potential consequences.” – Dr. Freeman [22:37]
  • Shared decision-making and transparent communication about knowns and unknowns are essential.

The 3 Essential Questions for Neurologists (23:48-28:52)

1. Who is the Right Candidate?

   • Clinical trials include highly selected participants; real-world MS patients have comorbidities and more diversity.
   • “How do we go from group-level data to individualized decisions? … Who is really progressing, or who is at risk of progression based on what’s happening within their brains? But we have no windows into that currently.” – Dr. Freeman [25:45]

2. When Is the Optimal Window to Intervene?

   • Progression in MS can be subtle or mistaken for other conditions (e.g., mobility impairment from arthritis, not MS).
   • Early identification is crucial, but current tools are lacking.

3. How Will We Know if Treatment Works for the Individual?

   • Unlike relapses or MRI lesions (easy to measure), progression can be hard to detect and attribute.
   • Need for new markers and better patient assessment tools.

• Dr. Freeman highlights the need for novel digital, blood, and imaging biomarkers:
  • “Digital biomarkers, serum biomarkers… and advanced imaging biomarkers can add tremendous specificity to characterizing and hopefully treating MS.” – Jon Strum [28:05]

Rethinking MS Disease Course Descriptors (29:35-32:42)

• Current descriptors (relapsing-remitting, secondary progressive, primary progressive) are outdated.
• Dr. Freeman: “MS is one disease. It’s a spectrum… We truly need course descriptors that reflect the underlying biology of MS and those different processes that are intertwined within each individual.” [29:37]
• Advocates for personalized, biology-driven assessment and monitoring tools, combined with collaboration between clinician and patient.

Notable Quotes & Memorable Moments

• On Limitations of Clinical Trials:
  “Clinical trial participants are very precisely selected... this may not look like most people living with MS, because people with MS don’t live just with MS.” – Dr. Freeman [24:48]

• On Shared Decision Making:
  “It’s really about engaging in a shared decision-making approach... making decisions together with some solid data, but also this approach to uncertainty.” – Dr. Freeman [23:11]

• On the Future of MS Care:
  “What we need to understand is... not just where they've been, but where they are going, what is at play in the brain, in the immune system.” – Dr. Freeman [30:41]

Important Timestamps

• 02:00-04:40 – USPS postmark changes and impact on health paperwork
• 04:45-08:45 – FDA decision on tolebrutinib and BTK inhibitors explained
• 08:46-12:10 – New biologically informed MS subtypes & personalized care implications
• 12:11-15:32 – Study on fear of progression in MS and mental health impact
• 15:33-17:17 – Experimental medicine trial awards and upcoming clinical studies
• 17:39-19:42 – Dr. Freeman introduces BTK inhibitors and their potential
• 19:42-22:05 – Real-world medication safety lessons from Tysabri and Gilenya
• 22:05-23:48 – Art and science of MS care; optimism and responsibility
• 23:48-28:52 – The 3 questions neurologists must ask in the BTK inhibitor era
• 29:35-32:42 – Re-evaluating MS course descriptors; push for biologically-guided care

Final Thoughts

This episode challenges both clinicians and patients to think critically about the future of MS treatment in an evolving era of biotechnology and personalized medicine. Dr. Freeman’s insights offer a roadmap toward more nuanced, evidence-based, and patient-centered care—emphasizing not only technological innovation but also the enduring necessity of vigilance, humility, and shared decision-making in MS management.

“It’s not just tools in a vacuum. It’s really tools that are used together... with our patients, with our sound decision-making so that we can make individualized decisions for each and everyone.” – Dr. Leorah Freeman [32:05]

For more from Dr. Freeman, check out her Substack: The Multiple Sclerosis Insider (link in show notes).