From the wheelchair to the bicycle: CAR-Ts achieve spectacular remissions against autoimmune diseases

The case of the first patient to receive immunological therapy against stiff person syndrome opens the door for the treatment to be used against other conditions, such as multiple sclerosis

Lilia, the first patient with stiff person syndrome to be treated with CAR-T, photographed a few days ago.EL PAIS
Nuño Domínguez

A few days ago, singer Céline Dion spoke about the rare disease that she suffers from and how it has hurt her professional life. “It’s like somebody’s strangling you,” she told NBC. The Canadian singer suffers from stiff person syndrome, an autoimmune disease that paralyzes different parts of the body, causing falls and making it difficult to walk. It is thought that this genetic disease affects only one person in a million. So far, only palliative treatments are available: there is no cure.

Lilia, a 69-year-old Venezuelan woman who has lived in Germany since the 1980s, received an experimental treatment that has proven highly effective against the same disease that affects Dion. Her case, recently described in the medical literature, has sparked hope for new treatments for stiff person syndrome and other autoimmune diseases that attack the central nervous system and are much more prevalent, such as multiple sclerosis.

On the phone from Bochum, Lilia (she prefers not to say her last name) describes her 10-year journey since she first began to experience symptoms. Stiffness in her legs and sudden falls. First, she needed crutches, then a walker, before ending up bedridden for several hospital admissions without any of her doctors giving her a clear diagnosis.

“I was in unbearable pain. I felt like my vertebrae were breaking inside my back. They suggested that it could be psychosomatic, but my body was talking to me,” says the retired administrator.

In 2014, she went to see neurologist Ralf Gold, who performed a genetic test and discovered that Lilia suffered from stiff person syndrome. The patient stopped responding to all available drugs. In 2023, Lilia was offered an experimental treatment: lymphocytes with chimeric antigen receptors, or CAR-T, a therapy that has revolutionized the treatment of blood tumors and that, in theory, could also work against her disease. The syndrome is characterized by a genetic defect in b cells, a type of white blood cell that produces harmful antibodies that hinder the transmission of nerve impulses and cause paralysis.

Since the treatment, Lilia has gone from needing a walker to go 50 meters to being able to go shopping and take 3.7-mile walks. She only continues to use the walker because she is afraid of falling, according to Gold, a neurologist at St. Josef Hospital in Bochum and the University of Jena in Germany. The doctor says that in his more than 35 years of experience, “he has never seen a similar response.” “This is a disease that is very difficult to treat and that destroys the body. In this patient, treatment with CAR-T has allowed her to recover quality of life. And in other cases, if it is detected earlier, the benefits could be greater,” he explains. The results have just been published in the journal PNAS.

Lilia received CAR-T against the CD19 protein. This means that the doctors extracted T-lymphocytes from her blood and genetically modified them to recognize this molecule, which protrudes from the surface of diseased white blood cells, and annihilate them. “The treatment reset the patient’s immune system. Today, her levels of harmful antibodies are very low,” says Gold. The treatment is made by the U.S. company Kyverna, which is testing it on patients with various types of early-stage autoimmune diseases (1 and 2).

Together with other specialists, the German neurologist has applied the same treatment to two patients with myasthenia gravis, another autoimmune disease mediated by antibodies that attack the body. The results, recently published, show complete remissions. One of the patients was 33 years old and, due to progressive paralysis, needed a wheelchair to move around and a machine to breathe. After receiving the CAR-T, the patient improved to the point of being able to ride an electric bicycle for more than 15 miles. “So far we have treated four patients with myasthenia gravis. The most striking case is a 74-year-old man who could not chew or swallow. One year after treatment, the disease is in complete remission, and he does not require any other medication,” says the German neurologist.

Since they began to be applied in 2011, CAR-Ts have cured achieved tens of thousands of patients with blood tumors. In 2022, these revolutionary treatments were also applied to people with systemic lupus erythematosus, another autoimmune disease that affects 0.1% of the world’s population, especially young women, achieving complete remissions.

Josep Dalmau, neurologist at the Hospital Clínic of Barcelona, was the supervisor of the study on Lilia, the first patient with stiff person syndrome to be treated with CAR-T therapy. “These treatments are being imported from cancer to autoimmune diseases, in this case to target them against cells that produce pathogenic antibodies,” he explains. “We’re seeing a trickle of spectacular first isolated cases, and we’re going to see more. In parallel, in the United States, there are about 12 more systematic clinical trials with a larger number of patients.”

The doctor explains that at his hospital they have developed their own CAR-T against CD19 and have used it to treat a man with a neurological autoimmune disease that had left him blind in one eye. The biggest fear was that the illness would soon affect the other. Although the patient has not yet recovered sight in his diseased eye, they have gone 14 months without relapses or needing more treatments, Dalmau details.

Another future application of CAR-T will be against multiple sclerosis, an autoimmune disease that represents a much greater challenge than those mentioned. A trial is already underway at Hospital Clínic of Barcelona. “In this case we do not know the culprit nor is there a specific antibody that causes this disease,” explains Dalmau. “But we do know that b cells have a crucial role. Although there are about 20 effective drugs against multiple sclerosis, sometimes none of them work. This happens especially in young patients who have a lot of disease burden in the spinal cord and brain. And we don’t know why. CAR-Ts might work better in these cases. It will be interesting to confirm if this is the case,” he concludes.

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