MS Living Well Podcast – Reengineering Hope: CAR-T Therapy for Multiple Sclerosis

Host: Dr. Barry Singer
Guests: Dr. Jeff Dunn (Stanford) & Dr. Amanda Piquet (University of Colorado)
Date: October 14, 2025

Episode Overview

This episode explores the promise and early experience of CAR-T cell therapy as a potentially transformative treatment for multiple sclerosis (MS). Dr. Singer talks to Dr. Jeff Dunn about the science behind CAR-T in MS, early trial results, patient experience, and why experts believe it could re-engineer hope for people living with progressive, treatment-resistant MS. Later, Dr. Amanda Piquet joins to discuss safety, risks, and the expansion of CAR-T into other autoimmune neurologic conditions.

Key Discussion Points & Insights

1. What is CAR-T Therapy? (02:02–04:16)

• Definition: CAR-T stands for Chimeric Antigen Receptor T-cell therapy.
• Analogy: “People can imagine their immune systems as their own personal military or secret service… CAR T cell is a really highly specialized, designed, engineered cell that has search and destroy functions altogether.” – Dr. Jeff Dunn (02:20)
• Engineering Process: Patient’s own T-cells are collected, genetically modified (using a virus carrying a new gene) to target specific cell-surface antigens (e.g., CD19 on B cells), then reinfused to attack problematic cells.

2. CAR-T in MS: Scientific Rationale (04:25–08:59)

• Targeting B Cells: CAR-T cells for MS are currently engineered to eliminate B cells by recognizing CD19, a molecule on their surface, including plasma cells that make antibodies.
• Potential Advantages Over Antibody Therapies:
  • Deeper tissue and CNS penetration (since T-cells can cross the blood-brain barrier, unlike monoclonal antibodies).
  • The possibility of targeting meningeal B cell follicles implicated in progressive MS.
• Quote: "CAR T therapies… circulate widely throughout the body, including the sanctuary sites of the central nervous system… offering deep tissue penetration for MS." – Dr. Dunn (06:29)

3. The Patient Experience: The Clinical Process (08:59–14:31)

• Collection: Patient undergoes apheresis (3–6 hours) to collect T-cells via a catheter in the arm or chest (09:09–10:58).
• Manufacturing: Cells are sent to a lab for engineering and expansion—a process taking about 4 weeks (11:24).
• Pre-treatment: Mild chemotherapy is administered before reinfusion to “make room” for the CAR-T cells (12:32–13:47).
• Infusion: A single IV push (usually 100 million cells over 10 minutes). “It’s remarkable how anticlimactic the infusion of CAR T cells actually is… surprisingly simple.” – Dr. Dunn (14:20)
• Hospital Stay: Patients remain hospitalized for at least 7–10 days post-infusion for close monitoring due to possible serious side effects (14:34).

4. Early Results and Patient Impact (15:24–19:08, 24:11–27:37)

• Side Effects: All patients experienced abrupt fever 10 days post-infusion—managed with hydration/acetaminophen (15:24).
• Efficacy: Robust proliferation of CAR-T cells, confirmed CNS penetration, and, in select cases, disappearance or reduction of oligoclonal bands (a diagnostic marker in MS) in spinal fluid (17:03–19:08).
• Immune Reset Concept: “We then see that the B cells will regrow... from the marrow without that infection, without that EBV Epstein Barr virus pollution... maybe this therapy provides a true immune reset.” – Dr. Dunn (19:15)
• ‘One-and-Done’ Potential: Theoretically, if effective, could be a single procedure offering long-term benefit—unlike current chronic therapies (20:28–21:36).
• Remarkable Outcomes: Patients reported a dramatic lift in fatigue and functional gains. One patient improved from being confined to transfers to walking 100 yards; another was able to walk Disneyland for 13 hours (25:58–26:46).
  • “Fatigue… seems as if it’s just lifted. What they describe… is they’re living like they used to years ago.” – Dr. Dunn (24:11)
• Caveat: Small patient numbers (six so far); larger, multi-center studies are needed.

5. How to Participate in CAR-T Trials (21:36–23:18)

• Ask your MS specialist or check clinicaltrials.gov for local recruiting sites.
• Current focus: progressive MS not responding to approved therapies.
• Quote: “Most of the trials… are phase one, which really focuses on safety and feasibility.” – Dr. Dunn (21:46)

6. Expert Optimism and Perspective (23:22–24:07)

• Dr. Dunn: “I have never been more excited about a therapy than this one. Never… I think there’s a chance that this process could eradicate the MS process in individuals, that it could truly provide an immune reset and cleanse them of this autoimmunity.”
• Urges continued focus on safety and further research.

Expanding CAR-T’s Horizon: Dr. Amanda Piquet Interview

1. Use in Other Autoimmune Neurologic Diseases (28:51–30:23)

• Active Research: Clinical trials for lupus, stiff person syndrome, myasthenia gravis, and case reports in neuromyelitis optica and autoimmune encephalitis.
• Quote: “Some of the responses… have been quite striking. Patients are experiencing improvements.” – Dr. Piquet (29:59)

2. CAR-T vs. Stem Cell Transplant (31:00–31:37)

• Both aim for immune reset, but:
  • Stem cell transplant ablates the entire adaptive immune system.
  • CAR-T is more targeted, removing specific cells (e.g., B cells), with less severe side effects.

3. Key Risks of CAR-T Therapy (31:51–39:36)

Cytokine Release Syndrome (CRS) (31:51–33:48)

• Symptoms: Fever, low blood pressure, shortness of breath—typically peaks within first 10 days after infusion.
• Management: Steroids, tocilizumab for severe cases.
• Generally milder in autoimmune diseases than cancer.

ICANS – Neurotoxicity (34:19–36:21)

• Symptoms: Confusion, speech difficulty, writing problems, in severe cases seizures.
• Management: High-dose IV steroids; often added seizure medication preventively (36:21).
• Linked to cerebral swelling; risk is lower in autoimmune patients than in cancer.

Infections, Cytopenias, and Monitoring (36:38–38:05)

• Immunosuppression: Risk of infection due to low B-cell (and sometimes broader blood count) depletion.
• Prevention: Protocols include prophylactic antivirals/antibiotics, sometimes IVIG.
• Monitoring: Patients advised to stay within close proximity to the treatment center for the first month post-infusion.

Long-term Safety: Cancer Risk (38:39–39:36)

• No clear data on secondary cancer risk in non-cancer populations yet; mandatory long-term monitoring (15 years required by FDA in some protocols).

4. Logistics & Practical Challenges (38:05–40:33)

• Geographic barriers for rural patients—a subject for future planning as therapy becomes more widespread.
• Currently, therapy is delivered on hematology or oncology floors, with neurology and hematology teams collaborating.

5. Quality of Life and Symptom Improvements (40:50–41:25)

• Patient Reports: Reductions in fatigue, improved mental clarity, decreased pain, and some regaining of lost function “which is not typically our mantra… but this is something that is incredibly encouraging.” – Dr. Piquet (41:11)

6. Final Advice to MS Community (41:36–42:14)

• “We’re at the very beginning of a paradigm shift… CAR T isn’t ready for widespread use yet… But it really does open a door that didn’t exist before.”
• Patients with aggressive or refractory MS may especially benefit in the future. Stay informed and consider clinical trial participation.

Notable Quotes & Memorable Moments

• Dr. Dunn (On patient improvement):
  "Fatigue... seems as if it’s just lifted. What they describe… is they’re living like they used to years ago, even before their diagnosis." (24:11)
• Dr. Dunn (On optimism):
  “I have never been more excited about a therapy than this one. Never… I think there’s a chance that this process could eradicate the MS process in individuals.” (23:28)
• Dr. Piquet (On paradigm shift):
  “We’re at the very beginning of a paradigm shift. CAR T isn’t ready for widespread use yet... But it really does open a door that didn’t exist before.” (41:36)
• Dr. Piquet (On collaboration):
  “It’s really a multi, multidisciplinary approach.” (40:21)

Important Segment Timestamps

| Segment | Timestamps | |---------------------------------------------|------------------| | What is CAR T Therapy? | 02:02–04:16 | | CAR T Mechanism & MS Application | 04:25–08:59 | | Patient Process & Logistics | 08:59–14:31 | | Early Results & Patient Impact | 15:24–19:08, 24:11–27:37 | | Trial Participation | 21:36–23:18 | | Risks: CRS, ICANS, Infection, Long-term | 31:51–39:36 | | Quality of Life & Outcomes | 40:50–41:25 | | Final Advice/Reflections | 41:36–42:14 |

Tone & Language

The episode maintains a hopeful, yet grounded, tone. Dr. Dunn is palpably excited about the prospects of CAR-T, frequently emphasizing “remarkable” and “amazing” patient outcomes, though careful to stress the preliminary nature of results. Dr. Piquet adds caution with an encouraging message—she’s clear about the risks and unknowns, insists on rigorous safety and long-term monitoring, and is enthusiastic about broader future applications.

Summary Takeaways

• CAR-T is a next-generation approach, potentially offering lasting remission via an “immune reset.”
  Early MS trials are promising: improved fatigue, some functional return, but numbers are small and safety is paramount.
• Process is complex and involves being hospitalized for treatment/monitoring, and currently restricted to clinical trials.
• Risks are significant but seemingly lower compared to cancer patients: fever, neurotoxicity, and infections are most common; long-term risks are still unknown.
• Practical access challenges and the need for multi-specialty coordination remain.
• If proven safe and effective, CAR-T could radically change future MS treatment, especially for severe, refractory cases.

For more detailed information, including links to ongoing clinical trials, listeners are encouraged to consult their MS specialist or visit clinicaltrials.gov.