A single infusion of engineered immune cells improved walking speed by at least 20% in 21 of 26 people with stiff person syndrome, a trial published Nov. 9 in JAMA Neurology found. By their last follow-up, every patient was off the other immune treatments they had used for the disease.
Stiff person syndrome is a rare autoimmune disorder that causes rigid muscles and painful spasms. A one-time treatment that lets patients stop ongoing immune therapy would change how the disease is managed, and four out of five patients in this trial crossed the bar researchers set for a meaningful response.
How the CAR-T Therapy Works
The therapy, mivocabtagene autoleucel, formerly called KYV-101, is made from each patient’s own T cells. Doctors engineer the cells to target CD19, a marker on B cells, the immune cells that make antibodies. In stiff person syndrome, antibodies attack the nervous system. The treatment wipes out the B cells and lets the immune system rebuild. Patients received one dose after a short course of low-dose chemotherapy. The trial, called KYSA-8, enrolled 27 patients at three U.S. sites from September 2024 to May 2025 and treated 26.
What the Stiff Person Syndrome Trial Found
The main measure was the time it took patients to walk 25 feet. At week 16, walking time improved by an average of 7.69 seconds, and the median improvement was 45.6%. Among 16 patients with 24 weeks of data, the median improvement was 44.4%. All secondary measures also improved.
Shari St. Germain, a trial patient who walked about seven miles a day before she got sick, described the change in a Mayo Clinic report. “I couldn’t believe it when I walked for 7 minutes on the treadmill,” she said. Another patient, Jonathan Walden, said, “I have not had one episode since receiving treatment.”
Side Effects and Limits of the Trial
Cytokine release syndrome, an immune reaction common with CAR-T, affected 24 of 26 patients, all at grade 1 or 2. Three had mild neurological side effects that resolved. Eleven patients, 42%, had grade 3 or 4 side effects, most often low white blood cell counts. One patient had severe neck swelling that required a breathing tube and resolved. No one died or left the trial because of side effects. The trial had no control group and was not blinded, and 26 patients is a small sample. Median follow-up was 6.5 months. Employees of Kyverna Therapeutics, which develops the therapy, are among the authors.
“What was most striking was the degree of improvement we saw in some patients,” said Dr. Anastasia Zekeridou, a neurologist and researcher at Mayo Clinic. She added that “the key question now is whether those improvements will be sustained over time.” Dr. Sean Pittock, chair of the Department of Neurology at Mayo Clinic in Rochester, said, “There is still much we need to learn, but this opens an exciting new avenue for the field.” Long-term follow-up of the patients is continuing.
