RealTalk MS — Episode 441: The 2026 ACTRIMS Forum

Host: Jon Strum
Guests: Dr. Manuel Friese, Dr. Amit Bar-Or, Dr. Haritha Desu
Date: February 9, 2026

Episode Overview

This episode kicks off Part 1 of RealTalk MS’s in-depth coverage of the 2026 ACTRIMS Forum, America’s foremost annual meeting dedicated to the latest advances in multiple sclerosis (MS) research and treatment. Host Jon Strum sits down with global leaders in the field—Dr. Manuel Friese, Dr. Amit Bar-Or, and up-and-coming investigator Dr. Haritha Desu—to discuss breakthroughs in understanding MS progression, the promise of emerging therapies, and key clinical trial results presented at the conference.

Key Discussion Points and Insights

1. Rethinking MS Progression and Neuroprotection

Guest: Dr. Manuel Friese (Director, Institute of Neuroimmunology and Multiple Sclerosis, Hamburg; 2026 Barancik Prize winner)

Neurons: Not Just Passive Victims

• Traditional view: The focus has been on stopping the immune system’s attacks.
• Dr. Friese’s shift: “We try to readjust our understanding... The progression of MS is still the most unmet clinical need in MS.” (03:33)
• The importance of studying how neurons themselves adapt (or fail to adapt) following inflammation.

Why Do People Progress Without Relapses?

• Even when MRIs show no new lesions, gradual worsening (progression) can occur.
• Friese proposes that neurons “have a response, a memory for the inflammation, and this is somehow what is determining their further outcome.” (05:03)
• Parallel drawn to other neurodegenerative diseases, with unique MS stressors (inflammation).

Energy Dysfunction in Neurons

• Inflammation forces neurons to downregulate energy production—possibly an evolutionary defense.

  “One way to really modulate infections is to shut down energy... the brain, the nerve cells still think that there is an infection around.” (06:44)

• Main challenge: Finding how to “lift the brake” on neuronal energy consumption without causing harm.

Nutrition and Neuroprotection

• Hopeful but cautious about diet alone making a major difference.
• The real issue seems to be neurons avoiding energy uptake rather than lacking nutrition.

  “The picture… is more the contrary, is that neurons consume too little energy actually because they are primed not to consume too much… they should actually again take all the energy up which they are getting provided.” (09:04)

• Talks about the difficulty of delivering protective nutrients directly to the brain; vitamin E is plentiful but not the solution.

Prospects for Neuroprotective Drugs

• Many immune therapies developed by “serendipitous finding.”
• Neuroprotection is a much greater challenge because of the complexity and essential nature of the nervous system.

  “I believe that the nervous system is even more complex than the immune system… taking out large chunks or courses of the nervous system is just not possible as it is in the immune system.” (11:32)

• Envisions a future with two kinds of drugs: one for immune modulation, one for neuroprotection, but stresses we’re “still quite some time” away. (11:32)

Empowering Patients in the Clinic

• Explains to patients that MS arises by chance—a “stochastic event”—and isn’t anyone’s fault.
• Striking, compassionate perspective:

  “They carry the burden… That everybody lives and can survive against infections and they carry the burden for humankind pretty much. Right? ...we should also heavily support these individuals because they are… giving the other individuals the allowance to really live and cherish without a disease.” (13:56)

2. Latest Clinical Trial Insights from ACTRIMS

Guest: Dr. Amit Bar-Or
(Director, Centre for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania)

Understanding MS Progression—Two Key Processes

• Relapsing: Waves of immune cells from outside the CNS causing visible attacks.
• Progressive: Ongoing inflammation inside the CNS, involving both persistent immune cells and activated resident brain cells (microglia, astrocytes).

  “Ideally we want to be able to target both those different aspects of the disease and perhaps ideally with a single agent.” (17:52)

BTK Inhibitors: How Are They Different?

• Standard B-cell therapies (like Ocrevus) are effective for relapses but “don’t typically get into the CNS at concentrations that in fact change the face of central nervous system inflammation.” (18:59)
• BTK inhibitors (especially those that cross the blood-brain barrier) can:
  • Impact B cells and myeloid cells outside the brain (relapse biology).
  • Target B cells and microglia inside the CNS (progressive biology).

Key Clinical Trials Presented

a) Moonstone Trial (Obexelimab, Week 12 Results)

• What is it? A phase 2 trial for obexelimab (a monoclonal antibody).
• Mechanism: Binds to CD19 and another B-cell receptor, delivering a negative signal (less activation, not just killing B cells).

  “Rather than just killing the cell... this antibody engaging the B cell changes its response to be less of a bad guy, less pro-inflammatory.” (20:04)

• Results:

  “The obexilimab arm decreased the development of new lesions by over 90%. It was highly effective at decreasing both gadolinium enhancing lesions as well as… new or enlarging T2 lesions.” (21:21)

b) Phase 3 Phentropid Study (Fenebrutinib vs. Ocrevus for Primary Progressive MS)

• Design: Non-inferiority trial to see if fenebrutinib (a BTK inhibitor) is at least as good as Ocrevus.
• Findings:

  “The study achieved its primary outcome... established non inferiority of fenebrutinib compared to ocrelizumab... people on fenebrutinib did a little bit better nominally than those on the ocrelizumab...” (~12% decrease in confirmed disability progression). (22:08-23:26)

Are We Getting Closer to Protecting Brain Health?

• Dr. Bar-Or: “I think we have just kind of gotten beyond the cusp and for the first time really with the class of the CNS penetrant BTKIs… the prospect of impacting the non-relapsing progressive disease.” (23:44)

What Makes ACTRIMS Special?

• Ms.-dedicated, single-track format, focus on discussion and young investigators.

  “It… emphasizes young emerging investigators and trainees in the field, which is a top priority for us...” (24:14)

3. The Next Generation of MS Research

Guest: Dr. Haritha Desu
(Postdoctoral neuroscientist, CHUM, Montreal)

Breaking the “Stickiness” of Immune Cells in the Brain

• Focus: How ICAM1 helps immune cells stick in the CNS, maintaining inflammation.

  “By making the cells less sticky and preventing them from staying in the brain, that means we can hopefully stop the damage that’s occurring and maybe even help the brain repair itself.” (26:45)

Beyond Entry Blockade: What Do Immune Cells Do Once Inside?

• Current therapies often stop immune cells from entering, but Desu’s work targets cells already resident in the CNS.
• If we can find accessible targets on immune cells still in the periphery (e.g., through the bloodstream), we may be able to drive them out of the brain or stop their harmful action.

TNFR2: A New Avenue for Repair

• Her graduate work suggests activating TNFR2 (tumor necrosis factor receptor 2) could stimulate repair, not just stop damage.

  “When we add an activating antibody, it can help reduce the inflammation.” (29:04)

• Still early: Challenge is getting drugs to act in the brain, but it’s a “very promising” direction.

NFL (Neurofilament Light Chain) as a Biomarker

• NFL is “not just a marker of more disease severity, but it also increases with age and there’s a lot of other factors… it’s not MS specific.” (29:59)
• New protein biomarkers to predict progression and therapy response are under active study.

Primary vs. Secondary Progressive MS—Same Disease, Different Speed

“I think the consensus in the field now is that it’s the same fire just burning at different speeds.” (31:32)

Notable Quotes & Memorable Moments

• Dr. Friese (on the patient journey):
  “There is no fault in having that disease, nothing which has been done wrong by the patient. ...they carry the burden... for humankind pretty much.” (13:56)

• Dr. Bar-Or (on BTK inhibitors):
  “For the first time really with the class of CNS penetrant BTKIs... the prospect of impacting the non-relapsing progressive disease.” (23:44)

• Dr. Desu (on progressive MS):
  “It’s the same fire just burning at different speeds.” (31:32)

Timestamps for Key Segments

• Introduction & Dr. Friese’s Profile: 00:01–03:13
• Dr. Friese on Neuroprotection & MS Progression: 03:13–13:56
• Dr. Bar-Or: Immune System & BTK Inhibitors: 17:41–19:49
• Moonstone Trial Results: 20:04–21:52
• Phentropid Study Results: 22:08–23:26
• Future of Brain Health in MS: 23:44–24:14
• ACTRIMS Forum Uniqueness: 24:14–25:15
• Dr. Desu: Sticky Immune Cells & Repair: 26:45–29:59
• Biomarkers/NFL Levels: 29:59–31:12
• Primary vs Secondary Progressive MS: 31:32

Episode Tone and Takeaways

The episode balances scientific rigor with empathy. Listeners gain an insider view of how cutting-edge research is reshaping our understanding of progression and neuroprotection in MS, and how young investigators are pushing the field forward. Notably, Dr. Friese’s perspective on the patient journey and Dr. Desu’s description of “the same fire burning at different speeds” give hope and context to people living with MS.

Whether you are living with MS, a caregiver, or simply interested in medical innovation, this episode offers thoughtful, jargon-free explanations straight from the world’s leading MS researchers.