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

A few days ago, singer Celine Dion gave an interview to describe the rare disease she has been suffering from for years and which has kept her from her professional life. “It’s like being strangled by a hand,” she described to NBC. The Canadian singer suffers from stiff-person syndrome, an autoimmune disease that paralyzes different parts of the body to the point of causing falls or preventing walking. It is thought that this genetic disease affects only one in a million people. So far, only palliative treatments are known, not a cure.

Without looking for it, Lilia, a 69-year-old Venezuelan woman who has lived in Germany since the 1980s, has received an experimental treatment that has proven highly effective against the same disease that affects Dion. Her case, recently described in the medical literature, opens up hope for the treatment of this 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 (who prefers not to give her last name) describes a 10-year ordeal since she began to feel the first symptoms. Stiffness in her legs, sudden falls, needing crutches first, then a walker, and then being bedridden for several hospital stays without any of her doctors giving her a clear diagnosis.

“I was in unbearable pain. I felt as if the vertebrae inside my back were breaking. They suggested to me that it could be something psychosomatic, but my body was speaking to me,” says this retired administrative worker.

In 2014 he went to the neurologist’s office Ralf Goldwho gave her a genetic test and found that she suffered from stiff-person syndrome. The patient stopped responding to all available drugs. In 2023, Lilia was offered an experimental treatment: chimeric antigen receptor-mediated lymphocytes, or CAR-T, a therapy that has revolutionized the treatment of blood tumors and could, in theory, also work for this 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 walk 50 metres to being able to go shopping and take walks of six kilometres. She only continues to use the walker because she is afraid of falling, according to Gold, a neurologist at the St. Josef Hospital in Bochum and the University of Jena. This doctor says that in his more than 35 years of experience “he has not seen a similar response”. “This is a very difficult disease to treat and it destroys the body. In this patient, the treatment with CAR-T has allowed her to recover her 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 of the National Academy of Sciences from the United States.

Lilia received CAR-T against the protein CD19. This means that doctors extracted T cells from her blood and genetically modified them so that they recognize this molecule, which protrudes from the surface of diseased white blood cells, and destroy them. “The treatment reset the patient’s immune system. Currently, her levels of harmful antibodies are very low,” Gold summarizes. The treatment is manufactured by the American company Kyvernawhich is testing it on patients with various types of autoimmune diseases in early stages (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, Just publishedshow complete remissions. One of the patients was 33 years old and due to progressive paralysis she needed a wheelchair to move and a machine to be able to breathe. After receiving CAR-T she improved to the point of being able to ride an electric bike again and do routes of more than 25 kilometers. “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 has completely remitted and he does not need any other medication,” says the German neurologist.

Since they were first used in 2011, CAR-Ts have achieved tens of thousands of complete cures in people with blood tumors. In 2022, these revolutionary treatments were also used in 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, a neurologist at the Hospital Clínic in Barcelona, ​​was the supervisor of the study on Lilia, the first patient with stiff-person syndrome treated with CAR T. “These treatments are being imported from cancer to autoimmune diseases, in this case to target the cells that produce pathogenic antibodies,” he explains. “We are seeing a trickle of spectacular first isolated cases, and we are going to see more. In parallel, in the United States there are about 12 more systematic clinical trials with a larger number of patients,” he highlights.

The doctor explains that at the Clínic 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 greatest fear was that the disease would soon affect the other. Although he has not yet managed to recover sight in the affected eye, the patient has gone 14 months without relapses or needing further treatment, Dalmau explains.

Another future application of CAR-T will be against multiple sclerosis, an autoimmune disease that poses a much greater challenge than those mentioned. At the Clínic they have a trial underway. “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 play 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 heavy disease burden in the spinal cord and brain. And we do not know why. CAR-T could work better in these cases. It will be interesting to confirm if this is the case,” he concludes.

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