CHICAGO — A single dose of an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy rapidly improved mobility and rigidity in patients with stiff person syndrome (SPS).

Early results of a phase 2 trial also showed the therapy — mivocabtagene autoleucel (miv-cel) — was well-tolerated and enabled patients to remain free of immunotherapies. 

“In my expert opinion, as someone who sees so many patients with stiff person syndrome, the results of this trial are truly remarkable,” lead trial investigator, Amanda L. Piquet, MD, director of the autoimmune neurology program at the University of Colorado Anschutz School of Medicine, and Celine Dion Foundation endowed chair, told Medscape Medical News. 

“I’ve just never seen outcomes that come close to delivering these types of benefits with the unapproved therapies that we use today in the clinic.”

The findings “are compelling and potentially paradigm changing for the SPS community” and could pave the way for miv-cel to become the first CAR T-cell therapy to be approved by the FDA for this autoimmune disease, she added during a press briefing. 

The findings were reported April 21, 2026 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

A Novel Treatment 

SPS is a rare, highly debilitating, neurological autoimmune disease characterized by progressive rigidity and painful spasms in the torso, arms, and legs. The condition gradually worsens over time and, if untreated, can lead to permanent disability and even death.

Public awareness of SPS increased after internationally renowned singer Celine Dion revealed her 2022 diagnosis and later chronicled her experience in the 2024 documentary I Am: Celine Dion.

There are currently no FDA-approved therapy for SPS, which affects about 1 in 1 million people.Unapproved treatments include high-dose benzodiazepines, other muscle relaxants, off-label immunotherapies such as intravenous immunoglobulin, plasmapheresis, and rituximab. Patients may also get relief from physical, speech, and occupational therapy. 

However, most SPS patients have inadequate or no response to medical treatment. About 80% of patients ultimately need some type of walking assistance or even a wheelchair, said Piquet. 

Autoimmune diseases involves B cells. In SPS, such involvement is supported by impaired GABAergic inhibitory transmission, with most patients exhibiting autoantibodies against glutamic acid decarboxylase (GAD). 

Miv-cel is an immune therapy made from a person’s own immune cells. “It’s a unique, fully human, autologous CD19 directed CAR-T therapy for B cell-driven autoimmune diseases,” said Piquet.

Using CAR T-cell technology, engineered T cells with receptors are designed to recognize and eliminate B cells, including those that produce GAD autoantibodies. This approach intervenes at the root of the autoimmune response.

‘Meaningful Functional Independence’ 

The small phase 2 study included 26 adults with SPS who had an inadequate response to at least one immunomodulatory therapy and a score of 2 or greater on the distribution-of-stiffness index (DSI), a scale ranging from no stiffness (0) and increasing by one point with the addition of stiffness to the face, arms, upper trunk, abdomen, lower trunk, and legs. 

To help prime the immune system, study participants received lymphodepletion before getting a single infusion of miv-cel (target dose 1×10⁸ CAR T cells).

The primary efficacy outcome was timed 25-foot walk (T25FW). After a median follow up of 6.5 months, the study showed statistically significant (P = .0003) improvement in T25FW of a median -4.8 seconds — which represented a 46 % median improvement — at week 16. 

Piquet noted that a 20% improvement is considered clinically meaningful, adding that about 81% of patients exceeded that threshold.

Of the 12 patients requiring a walking aid at baseline, two-thirds (67%) no longer needed assistance at week 16, which Piquet said reflects “meaningful functional independence.” 

Miv-cel was well-tolerated with a manageable safety profile. There was no high-grade cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome; lower-grade CRS occurred in 92.3% of patients, but all resolved without sequelae. Other treatment-related adverse events included fatigue (54%), diarrhea (38%), and headache (31%). 

Some patients (15.4%) experienced grade 3/4 neutropenia, a known adverse event associated with CAR-T treatments, but this was manageable. Deep B-cell depletion was observed, which is associated with immune reset. 

All study participants remained free of immunotherapies, and no patients required rescue therapy as of the last follow up. This highlights the potential of miv-cel’s ability to provide clinical benefit while significantly reducing or eliminating chronic treatment burden. 

The study also showed highly statistically significant benefits on all secondary efficacy endpoints, including scores on the modified Rankin Scale (mean improvement of -0.8); Hauser Ambulation Index (-1.6); SPS-specific measures of DSI (-1.5) and heightened sensitivity scale (-3.2). (The P values were < .0001 on all scales.) 

‘Transformative Outcomes’ 

“These transformative outcomes were possible through the ability of miv-cel to deliver this deep B cell depletion and broad immune reset,” said Piquet. “From a clinical perspective, the magnitude and consistency of functional improvement observed is unprecedented.” 

Asked if patients require more than the one infusion, Piquet said the therapy “has the potential for being ‘one and done.’” 

Based on these positive data, the sponsoring company, Kyverna Therapeutics, is preparing to submit a biologics license application to the FDA for SPS. The company has received both regenerative medicine advanced therapy and orphan drug designations for miv-cel in this indication. 

CAR T-cell therapy is being investigated in oncology and in other autoimmune diseases, including myasthenia gravis and multiple sclerosis, said Piquet. “This new data gives a lot of hope to patients, their families, and physicians, not only with SPS, but also with other autoimmune neurologic diseases.” 

Commenting on the findings, Max Herman, MD, a member of the AAN Autoimmune Neurology Education committee and an autoimmune neurology fellow, Mayo Clinic, Jacksonville, Florida, said — despite the study’s small sample size — the study results could “represent a breakthrough therapy for SPS patients.” 

“Historically, this condition is very hard to treat, and who will respond to immunotherapy is highly variable. The fact that so many patients saw some form of improvement speaks volumes to the potential efficacy of this treatment,” he told Medscape Medical News. 

He added that SPS patients may have other presentations, including cerebellar ataxia with GAD65 antibodies, or glycine receptor antibody encephalopathy.

“It will be interesting to see if there are also improvements in these symptoms and, if so, it could represent a breakthrough therapy for multiple diseases related to these autoantibodies.”

He said he is curious whether CD19 CAR-T therapy offers additional benefit beyond lymphodepletion alone.

“There has been historical success with treating some patients with lymphodepleting chemotherapies like cyclophosphamide, so what degree of this improvement is due to the initial lymphodepletion remains to be seen.”

He added that longer-term data from phase 3 studies will be important. “It remains to be seen if the positive changes are sustained over time.”

He added that he is curious about whether patients treated with CD19 CAR-T would do better than those who have been lymphodepleted but don’t receive CAR-T treatment. 

“There has been historical success with treating some patients with lymphodepleting chemotherapies like cyclophosphamide, so what degree of this improvement is due to the initial lymphodepletion remains to be seen.”

The study was sponsored by Kyverna Therapeutics. Piquet has received grants or contracts from the Celine Dion Foundation, Foundation for Sarcoidosis, Genentech/Roche, and Kyverna Therapeutics, as well as consulting fees and honoraria from various groups. Herman reports no relevant conflicts of interest.