This ‘living drug’ could change the course of autoimmune disease

Two months before the treatment that would change Lynn Montgomery-Haga’s life, she could barely walk down a hallway.

In a test at the University of Colorado Anschutz, Montgomery-Haga struggled to walk 25 feet, often reaching out to the walls for support. Usually, the 49-year-old relied on her walker or wheelchair. “She had a very stiff, hesitant gait,” says Montgomery-Haga’s neurologist, Amanda Piquet.

For about a decade, Montgomery-Haga had lived with a debilitating autoimmune disease known as stiff person syndrome. The progressive condition can lock up the body’s muscles without warning, leading to falls, broken bones, excruciating pain and difficulty moving. Singer Celine Dion, who returned to the stage in September after years of battling the disease, has said it can feel “like somebody’s strangling you.”

Montgomery-Haga’s own days were marked by dizziness, fatigue and pain. And sudden muscle spasms would send her sprawling. It was like the fainting goat videos popular on the internet, she says. “They get surprised and they fall over, and there’s nothing they can do about it.”

But stiff person syndrome is no joke. It stripped Montgomery-Haga of her accounting job and her ability to drive. She couldn’t sit up in bed unless she had a safety bar to pull on. If she dropped the soap in the shower, it’d take her 10 minutes to pick it up.

Now, Montgomery-Haga hopes those struggles are finally coming to an end. That’s because a clinical trial with an experimental therapy has helped restore mobility for her — and others like her. She can stride through her living room again. She can landscape her front yard. She doesn’t have to brace herself when her dogs jump on her. And she hasn’t fallen once since the treatment. The change has been drastic, she says. “I’m just really excited about the future.”

The treatment, a type of CAR T cell therapy, extracts immune cells from a person’s body and engineers them to attack the very cells causing the disease. First used to fight cancer, CAR T is now also targeting a variety of autoimmune diseases. If given the green light by the U.S. Food and Drug Administration, Montgomery-Haga’s treatment would be the first such therapy approved for an autoimmune condition — and it would be the first approved treatment for stiff person syndrome.

Stiff person syndrome may be just the beginning, says Carl June, the University of Pennsylvania immunologist and oncologist who spearheaded CAR T cell therapy for cancer decades ago. The “living drug” could herald a new era of therapeutics for autoimmune diseases like lupus, rheumatoid arthritis and even multiple sclerosis. “It’s revolutionary to think how far things have gone,” June says.

But he warns that it’s far too early to know if scientists have definitively cured stiff person syndrome. And there haven’t been enough people treated to get a good handle on all the possible side effects. “There could be long-term complications in autoimmune patients that don’t happen in our cancer patients,” he says. Other researchers urge caution. “It’s very important not to oversell it,” says Marc Scherlinger, a rheumatologist at Strasbourg University Hospital in France.

For Piquet, one crucial question is how long the treatment will last. In Montgomery-Haga’s case, the answer seems to be at least two years. Montgomery-Haga still considers herself disabled, or “disabled-ish,” as she calls it. But when rating how she used to feel on a scale of one to 10, she’d put herself at a zero before treatment, she says. These days, she’s more like a seven.

What’s more, Montgomery-Haga says, “I think I’m still improving.”

No approved therapies

There’s no single symptom that clued Montgomery-Haga in to her disease. In 2014, she started having difficulty picking things up off the floor. Then her boss asked her why she was limping — Montgomery-Haga hadn’t noticed. Her balance was off and her head felt weird, like “I was walking around in a fishbowl,” she says. It got to the point where Montgomery-Haga had difficulty crossing thresholds between rooms.

Montgomery-Haga would startle easily, prompting her body to stiffen up like a board. One time when cooking, she burned her finger, spasmed and collapsed, cracking the back of her head on the cabinets. She lay on the floor crying, but finally managed to right herself. “As soon as you hit the floor,” she says, “your muscles are like, ‘Fine,’ and you can get up again.”

Those unpredictable symptoms capture a slice of what life is like with stiff person syndrome, or SPS. The disease, which affects roughly 2 in 100,000 people in the United States, typically develops in a person’s 30s or 40s. It is about twice as common in women as in men.

Scientists don’t know what sets off the disease. But they think a person’s own antibodies start attacking a neurological network that helps muscles throughout the body relax. And when those tensed muscles are in opposition, like the biceps and triceps, they start fighting one another, Piquet says. That’s when people can end up in a stuck position, leading to stiffness. But because everyone’s immune system is different, patients’ experiences with the disease can vary greatly.

For Tara Zier, a former dentist based in Maryland, SPS started with extreme neck pain, blood pressure spikes, shortness of breath and feelings of impending doom. While some people struggle with mobility, Zier’s difficulties include standing and extreme fatigue. When she holds herself upright, her muscles clamp down on her spine like it’s in a vise. “Have you ever had a charley horse in your calf?” she asks. “Imagine one in your whole body that stops you in your tracks.”

Zier and Montgomery-Haga went years before learning what was behind their symptoms. Their cases mystified doctors — Zier saw 13 specialists and visited the emergency room nine times before getting a diagnosis. When she finally found out she had SPS three years after her first symptoms, Zier says she felt validated, like medicine was confirming what she already knew: “Something’s wrong with me.”

Montgomery-Haga’s 2018 diagnosis put her “over the moon,” she says. For nearly four years, she had gotten sicker and sicker — but doctors couldn’t tell her why. She felt as if they were giving up on her. With the diagnosis, Montgomery-Haga not only learned that SPS existed, she says, “I was told it’s treatable.”

Current treatments include muscle relaxers, anti-seizure medications and Botox injections in body parts that feel especially stiff. Although these off-label therapies can address people’s symptoms, they’re “doing nothing to treat the underlying autoimmune disease,” Piquet says. And some can come with potent side effects, like mental fog.

Zier, who has tried multiple combinations of different meds, remembers frequently losing her train of thought. She has since tapered off all but one drug, a low dose of Valium. “The trade-off,” she says, “is pain.”

People with SPS can also receive intravenous infusions of healthy antibodies, a treatment called IVIG, to decrease muscle spasms and stiffness. Montgomery-Haga found it helpful but time-consuming. She’d go to the clinic every three weeks for an infusion, which could take up to six hours.

“The bottom line is there are no FDA-approved therapies for this disease,” Piquet says. Now, the one most likely to cross the finish line first is something no one would have expected even a few years ago, CAR T pioneer June says. If you told doctors that CAR T cell therapy was going to be FDA approved for an autoimmune disease, he says, “people would have laughed.”

To catch a killer

June may be best known for his work in cancer, but he’s been keenly following the progress in auto-immune therapy. His daughter, now in her 30s, was diagnosed with juvenile rheumatoid arthritis when she was 9 years old. For her, that’s meant over 20 years of treatment with drugs that bring a bundle of side effects, such as fatigue and risk of infections. “It would be much better to be cured,” he says.

In autoimmune diseases like rheumatoid arthritis, lupus and SPS, a person’s own antibodies attack tissues throughout the body, from blood vessels to cartilage to neurons. Wiping out these rogue antibodies can stop the attacks. But CAR T cell therapy doesn’t act on the antibodies themselves. It goes straight to the source, snuffing out the cellular factories that manufacture them.

Those antibody factories are known as B cells. To eliminate them, doctors recruit T cells, which act as the body’s security system and work together to hunt down and destroy problematic cells. In the lab, scientists fine-tune these hunters, outfitting them with a molecular homing device called a chimeric antigen receptor, or CAR. When infused back into patients’ bodies, the newly-engineered T cells can target the antibody factories directly — like a saboteur told exactly what to destroy.

“The secret behind CAR T cell therapy is that you completely deplete B cells in the body,” says Georg Schett, a rheumatologist at Friedrich-Alexander-Universität Erlangen-Nürnberg in Germany. Temporarily wiping out a person’s B cells lets the body replace them with fresh, unproblematic ones, Schett says. He calls it an “immune reset.”

CAR T cell therapy got its start in the 2010s, when researchers used engineered T cells to target cancer. In 2017, the FDA approved the first CAR T cell therapies for two blood cancers, acute lymphoblastic leukemia and large B cell lymphoma. Soon after, scientists saw the first tantalizing hints that it might work for autoimmune diseases, too. In some cases, cancer patients with autoimmune disorders reported improvements in both conditions after treatment.

But most researchers didn’t think it could be that easy, Schett says. After all, autoimmune diseases were driven by a complex network of cell types. How could targeting just one of them work?

That thinking underwent a paradigm shift in 2021 when Schett and his team published the first major paper reporting a successful treatment with the therapy. The patient was a 20-year-old woman with a severe case of lupus, a complex, sometimes-fatal illness that can damage the kidneys and other organs. Within five weeks of CAR T cell therapy treatment, signs of her disease began to vanish.

Results like these were “unheard of,” says rheumatologist Maximilian Konig of Johns Hopkins Medicine in Baltimore. Lupus is extremely difficult to treat, and for decades, most drugs tested against it failed. No one had ever seen the kind of improvements that Schett’s patient experienced.

After the paper came out, “everybody was talking about it,” Konig says. Today, more than five years later, the woman’s lupus hasn’t returned, Schett says. “We consider this patient cured,” he says.

The woman’s response was no fluke. The following year, Schett’s team reported similar results in five more lupus patients. All went into remission after CAR T cell therapy.

This was the true tipping point, June says. “It’s rare, very rare, that you get such striking results.”

What followed was an explosion of research around the world. Scientists are now testing CAR T cell therapy in nearly a dozen autoimmune diseases linked to harmful B cells, including lupus, rheumatoid arthritis and a connective-tissue disease known as systemic sclerosis.

Kyverna, the California-based company behind the SPS trial, is also running trials for neurological autoimmune conditions including generalized myasthenia gravis and progressive multiple sclerosis, or MS.

One reason using CAR T cell therapy for neurological conditions excites researchers is because of the cells’ potential to slip past the blood-brain barrier. That means they might be able to access pockets of smoldering inflammation inaccessible to other drugs, says neurologist Rebecca Farber of Columbia University.

That could be a huge help in diseases like MS, in which a person’s antibodies attack the protective sheaths around nerve cells, causing numbness, brain fog and difficulty walking. Still, Farber doubts that CAR T cell therapy could fix existing damage. “We’re not expecting it to repair the nervous system,” she says. But it’s possible the treatment could freeze the disease’s progress. Patients are already asking her team about future treatments.

For Piquet, who cares for roughly 100 people with SPS, Kyverna’s trial offered a compelling opportunity to help her patients. Montgomery-Haga cried when Piquet told her about the trial at one of their regular Zoom appointments. She recalls wondering, is this the treatment that “might help me be normal again?”

The good, the bad and the potentially ugly

Though Montgomery-Haga leapt at the chance to try Kyverna’s treatment, called miv-cel, CAR T cell therapy is no walk in the park. Before starting, doctors sit patients down to “talk about the good, the bad and the potentially ugly,” Piquet says.

That includes the rigorous prep work needed before people receive their engineered T cells. Patients must first get low-dose chemotherapy, which flushes T cells from the body and makes space for the new ones. Chemo can ambush the body with symptoms including hair thinning, nausea, vomiting and diarrhea. 

Treatment itself also carries risks. It destroys most B cells in the body — not just the ones that cause disease. That can lead to fever, inflammation and potentially risky infections. In Kyverna’s trial, for example, 15 percent of participants had severely low white blood cell counts after treatment. Such symptoms were expected, Piquet says, and were easily treated.

Other CAR T treatments seem to have fared far worse. In August, the pharmaceutical company Novartis paused clinical trials of its therapy, rap-cel, across a spectrum of autoimmune diseases after three patients died. Bristol Myers Squibb has also paused similar studies after some patients experienced neurological complications, according to the Wall Street Journal. Details of the incidents were slow to emerge and have set the field on edge. “It’s a tragedy,” Konig says. He calls such outcomes an important wake-up call.

But red flags in one trial don’t mean all CAR T products are dangerous, Konig says. That’s because many different designs and manufacturing processes exist, and scientists can’t always predict what will make one product toxic and another safe. Kyverna’s miv-cel, for instance, has been consistently well-tolerated in the more than 100 patients treated, a spokesperson for the company says.

CAR T cell therapies are transformative, Konig says. “They’re going to change the field — but there are risks.”

Another risk is that the once-vanquished disease will return. Doctors don’t know all the genetic and environmental conditions that trigger autoimmune disease. Some researchers wonder whether vulnerable individuals remain vulnerable, even after treatment. But because it often takes multiple insults for someone to tip into a state of disease, Scherlinger says, CAR T cell therapy could buy patients lots of time.

“Now I can”

After 10 days in the hospital for her treatment, Montgomery-Haga returned to recover at home. In the following months, she started to notice some changes. It was easier getting around the house, for one. And she felt her balance and stability improving. She can now kneel down to garden and clean without the days of recovery it used to require. “I can vacuum my house,” she says. “It seems so little, but now I can vacuum!”

Montgomery-Haga can even sit down “crisscross applesauce,” she says. “I couldn’t do that for, like, 10 years.”

Four months after the treatment, Piquet’s team tested Montgomery-Haga’s walking ability. In a hallway at University of Colorado Anschutz’s research building, the team marked out 25 feet with little orange cones. At one end stood Montgomery-Haga. At the other, Piquet watched behind a video camera. This time, Montgomery-Haga’s gait was smooth and her arms were down, not hovering out into the air to catch herself if she fell. “You could see that she was walking with a lot more confidence,” Piquet says.

The team saw similar results in other SPS patients. Some who had difficulty walking before treatment now wanted to run, Piquet says. “It’s incredible to just see those patients speeding down the hallway.” She remembers smiles, high fives and a sense of celebration in the air. Eight of 12 people who had used a walking aid for the initial test didn’t need one for the follow-up, Piquet reported at the American Academy of Neurology meeting in April.

In September, Kyverna reported the trial’s one-year results: Patients maintained mobility improvements, with a third completing their 25-foot walk about as fast as a healthy adult. Additionally, nearly all patients no longer rely on immuno-suppressive drugs to tamp down harmful immune activity. That’s good news because such drugs can bring all sorts of nasty side effects, like vomiting, bleeding and infections.

The results with SPS are “really something to celebrate,” June says. But only time and many more treatments will reveal how safe CAR T really is, he says.

That’s a concern for Zier, who says she wouldn’t feel comfortable trying the therapy at this point. Zier doesn’t know how she’d respond. She’s a single mother with two kids; even a rare side effect could disrupt her life in a way she may not be able to manage. And these days, she’s managing as well as she can. Zier is the founder and CEO of The Stiff Person Syndrome Research Foundation, which supports research for SPS treatments.

Kyverna is in the process of submitting miv-cel for FDA approval. The company is seeking priority review and hopes the treatment might be available to patients in 2027. If SPS is the first autoimmune disease to have an FDA-approved CAR T cell therapy, myasthenia gravis could be the second, says Warner Biddle, Kyverna’s CEO. What’s more, miv-cel also appeared to improve symptoms in six patients with severe cases of rheumatoid arthritis, researchers reported in August in Nature Medicine.

As for what’s next, the door is wide open. Some scientists are working to make off-the-shelf forms of CAR T that wouldn’t require personalized engineering. Others are trying to reprogram T cells directly inside people’s bodies, rather than in the lab. Still others are trying to make T cells that target only the B cells responsible for disease. In the future, doctors might use such drugs to help patients avoid the cumbersome treatment process that Montgomery-Haga endured.

Montgomery-Haga’s own future looks far different than what she had imagined a few years ago. In 2026, she took a trip to Washington, D.C., to see the monuments. Now she’d like to visit Paris, Scotland and Ireland, too.

For so many years, Montgomery-Haga has looked at trips and activities — and even household chores — that most people take for granted, thinking, “Man, I wish I could do that,” she says. “Now I can.”