When asked if she could walk unassisted after taking part in a clinical trial, Lynn Montgomery-Haga jumps up from her chair and does a quick lap around the tables of her small town’s only coffee shop. At the end, the longtime Milliken, Colo., resident throws her arms in the air, taking a “ta-da!”-like pose.
The answer was a definite yes.
The seemingly small feat went unnoticed by the customers filling the place with chatter on a mid-morning weekday. But it represented a major victory for Montgomery-Haga and – the hope is – for millions of other patients who suffer from autoimmune diseases.
Diagnosed with stiff person syndrome (SPS) in 2018 after an agonizing four years of not knowing what was wrong with her body, Montgomery-Haga was the first person enrolled in a recent CAR (chimeric antigen receptor) T-cell therapy clinical trial for the disease at the University of Colorado Anschutz. At 12 months out, she’s still walking – instead of wheeling – around her home.
Of the 12 participants with stiff person syndrome who needed walking aids at the start of the landmark clinical trial, eight no longer required assistance to walk a 25-foot timed test at the 16-week mark. In that time period, 81% of the 26 participants demonstrated a clinically significant increase in walking speed.
“And a third of participants were able to walk at the speed of a healthy adult, which is around 25 feet in four seconds,” said Amanda Piquet, MD, primary investigator of the three-site clinical trial and renowned expert in SPS. “So, yes, pretty impressive.”
If the trial’s results are strong enough to earn a Food and Drug Administration nod in the next few months, it will be the first FDA-approved treatment for SPS and the first CAR T-cell therapy ever approved for an autoimmune disease.
The scope: Upward of 15 million Americans live with an autoimmune disease, between 60% and 80% of them women.
“The go-to therapy for stiff person syndrome is IVIG, or intravenous immune globulin,” said Piquet, founder and director of the Autoimmune Neurology Program at the University of Colorado Anschutz, one of only three such programs in the country. “But it’s not always sustained,” she said.
“There is some literature out there that suggests that about a third of patients continue to progress years after the initiation of IVIG,” she said. “So we definitely need better therapeutics.”
Called miv-cel (mivocabtagene autoleucel), the novel CAR T-cell therapy achieved statistically significant clinical benefit across all primary and secondary endpoints of the trial after one dose, reversing disability and eliminating the need for other immunotherapies, according to the sponsoring biopharmaceutical company, Kyverna Therapeutics, Inc.
“The hope is that this is a one-and-done treatment,” Piquet said, noting that trial participants will be followed for at least 15 years.
With autoimmune diseases, something goes awry, causing a person’s own immune system to attack itself. In the case of SPS, scientists believe B cells malfunction, producing excess GAD65 antibodies.
When a doctor finally sent Montgomery-Haga to CU Anschutz after four years of appointments, tests and stumped providers, a blood test showed her GAD65 level at 1,087. Normal is below 0.02.
With SPS, a neurological autoimmune disease, the army of GAD65 antibodies block important GABA receptors in the brain and spinal cord. These receptors function as a brake for the central nervous system by relaxing muscles after they contract. The malfunction leads to overexcitement of the muscles, causing debilitating stiffness and painful spasms throughout a person’s trunk and limbs.
For Montgomery-Haga, flares would often hit out of nowhere, causing her to stiffen like a board and then just crash to the floor. Other times, triggers (stress, bright light, loud sounds, unexpected touch, tripping hazards) would bring on episodes.
“Once, I reached forward to shake a client’s hand and, boom! Flat on the floor,” said Montgomery-Haga, who commuted from her northern Colorado town to Boulder for a senior tax accountant job before her then-undiagnosed SPS prevented it. The disease is progressive, especially untreated, landing her in a wheelchair within two years.
Another time, Montgomery-Haga burned her finger slightly while cooking, and her husband found her on her back unable to move, sandwiched between the oven door and the floor.
“If you’re falling, don’t grab an oven door. They open,” she said, able to joke now about incidents that then – not knowing what was wrong – had her terrified and in tears.
With CAR T-cell therapy, a patient’s own T cells are removed, modified in the lab to target the rogue B cells, and then re-infused in the patient during hospitalization. The groundbreaking therapy debuted in oncology, transforming blood-cancer care by engineering T cells to attack cancer cells.
Flu-like symptoms from the therapy marked her 10 days in the hospital, Montgomery-Haga said. “And then, it just started getting better, as the T cells did their thing, knocking out the bad B cells. Then I started to be able to walk again,” she said, adding that she continues to have fewer episodes and symptoms.
Piquet said she believes CAR T-cell therapy has the potential to transform autoimmune disease care as it has cancer, and the hope is that this SPS trial serves as a pathway to that end.
The therapy was well-tolerated by trial patients, with no reported cases of the primary toxicity-related side effects.
“What this CAR T therapy is able to do, which our other therapeutics cannot do, is get to a deeper depletion of the B cells,” Piquet said. “It's more rapid, and it crosses the blood-brain barrier. And so it basically wipes out all of the B cells. Then eventually, over time, you have a reset of the immune system because you have nice healthy B cells populating.”
While approval of a therapy would be a major win for SPS patients, creating uniform diagnostic criteria and raising awareness of the disease (helped by patient Céline Dion’s SPS diagnosis reveal in 2022) also sit high on Piquet’s agenda.
“The average time to diagnosis is seven years,” said Piquet, the inaugural Céline Dion Foundation Endowed Chair in Autoimmune Neurology who treats the famous singer. As with most autoimmune diseases, symptoms range widely with SPS, making it difficult to diagnose, she said. Misdiagnoses of other diseases, such as multiple sclerosis and Parkinson’s disease, are common, she said.
The emotional toll of the disease, especially when undiagnosed, can cause depression, anxiety and phobias, Piquet said. “Patients report that their environment becomes very small.”
For Montgomery-Haga, fear of episodes in public provoked social anxiety, and the weight of not knowing what was wrong triggered bouts of depression, marking the years from 2014 to 2018. “I didn't want to go anywhere, unless it was with my husband, because he's my safety net,” she said.
Losing her job she worked hard for and her independence her mother instilled in her were also difficult for Montgomery-Haga. "She taught my two sisters and me to be independent. And then I wasn't anymore. And it's so hard to rely on other people, especially when you’re used to doing things for them," she said.
“Sometimes, I would just sit on my bed in the dark and cry,” she said, emphasizing that professional mental health support is crucial.
CU Anschutz to host SPS symposium
Patients, advocates and top world experts of stiff person syndrome (SPS) will converge June 13-14 on campus for the 2026 SPS Symposium. Amanda Piquet, MD, will share highlights of the CAR T-cell therapy clinical trial for SPS. Topics will focus on treatments, emerging science and lived experiences. More information.
At one point, a neurologist told her she just needed to accept it, that this was just how she was going to be.
Luckily for Montgomery-Haga, her primary care doctor refused that prognosis and called around until he landed at CU Anschutz, now a destination hospital for SPS treatment. Piquet officially diagnosed Montgomery-Haga in 2018 and has taken care of her ever since.
“I’m so thankful to have access to such great care,” Montgomery-Haga said. And the results have been “amazing,” she said, offering two pieces of advice for people newly dealing with SPS. One, don’t dwell on other patients’ journeys. “Focus on your own. No two cases are alike.” And two, “Chin up. There is hope.”
Photo at top: Lynn Montgomery-Haga smiles as she poses standing next to an empty wheelchair on campus.
Key points:
- A CAR T-cell clinical trial for stiff person syndrome showed a clinical significant increase in walking speed for 81% of the 26 participants at the 16-week mark.
- After receiving the therapy, eight of the 12 trial participants who required wheelchairs or other walking aids before the trial could walk freely during a 25-foot timed test.
- If it receives federal approval, it will be the first Food and Drug Administration-approved therapy for stiff person syndrome and the first CAR T-cell therapy approval for any autoimmune disease.
- Experts hope this regenerative therapy can reset patients’ immune systems and potentially halt disease progression.