The legendary pop diva
Celine Dion has earned numerous honors throughout her life, winning two Grammy Awards and being awarded the French Legion of Honor. She is hailed as a “legendary pop diva” and the “queen of adult contemporary music”…
The theme song “My Heart Will Go On,” which she sang for the movie “Titanic,” has become one of the world’s best-selling singles and is sung all over the world. In addition to her various accolades, Celine Dion also has another identity – a patient with stiff-person syndrome.
Stiff-person syndrome (SPS), a name that sounds quite terrifying in Chinese, actually represents a rare autoimmune central nervous system disease.
According to statistics, the annual incidence rate of SPS is about 1-2/100,000, with a male-to-female ratio of about 3:1, and the age range is mostly between 20-50 years old.
The disease starts insidiously and is difficult to diagnose. The typical symptom, as the name “stiff person” suggests, is progressive muscle stiffness.
Sudden noises, emotional stress, and tactile stimuli can trigger muscle rigidity or painful spasms, and patients, due to the lack of normal motor responses, exhibit a unique statue-like or wooden fall.
This is undoubtedly fatal for a singer.
A month before the opening of the Paris Olympics, Celine Dion released her latest documentary “I am: Celine Dion.”
In the film, Celine Dion publicly revealed her stiff-person syndrome attack for the first time. During the attack, she was unable to control her breathing, and the spasm lasted for ten minutes.
Celine Dion, who suffers from SPS, had her vocal cords affected back in 2017 ago and was only diagnosed in 2022. The opening ceremony of this Olympic Games was her first public appearance since she stopped performing after the diagnosis.
Celine Dion’s comeback has once again brought the disease SPS into the public eye, and foundations and pharmaceutical companies in this field have also received media attention accordingly.
Another patient
“I am very happy for her that she can do this.” Tara Zier, the founder and CEO of the Stiff Person Syndrome Research Foundation (SPSRF), commented on Celine Dion.
Tara Zier is also a patient with SPS.
Once, Zier was a dentist and a karate enthusiast, with the strength of a third-degree black belt. In 2014, after the death of her loved one, her health took a sharp turn for the worse, exhibiting symptoms such as difficulty breathing, fatigue, severe pain, and difficulty eating.
Misfortunes never come singly. Zier’s symptoms continued to worsen, and by 2017, she was unable to work, drive, take care of herself, or her children, and was eventually diagnosed with SPS after several twists and turns.
In 2019, Zier established the SPSRF. It is worth noting that a member of the medical advisory board of the SPSRF, Amanda Piquet, is the doctor who diagnosed Celine Dion with SPS.
“Not all neurologists are familiar with this disease (SPS), so patients usually have to go through a long diagnostic process,” Piquet said in an interview. “In one study, the average diagnostic time for this disease was found to be about 7 years, and in some cases up to 19 years.”
This is because there is no internationally recognized diagnostic standard for SPS. In clinical practice, doctors often use electromyography and blood tests to help confirm the diagnosis.
Among them, the high level of serum GAD65 antibodies related to neurological syndromes is considered an important indicator that SPS is an immune-mediated etiology.
As early as 1998, there was evidence that the vast majority (> 95%) of GAD antibody-positive SPS patients have very high antibody titers.
It is worth noting that the final diagnosis of SPS also needs to exclude spinal and extrapyramidal diseases, because GAD antibodies can be positive in healthy people as well as in other neurological diseases, and some SPS patients are negative for GAD antibodies.
Even though it is not yet clear whether low-titer serum GAD65 antibodies and other neuronal cell surface antibodies are related to different clinical syndromes.
However, relevant clinical research on SPS has already begun.
The possibility of cure by CAR-T?
GAD65 antibodies are produced by dysfunctional B cells, which interfere with the formation of the neurotransmitter GABA, thereby inhibiting the nervous system.
In layman’s terms, under normal circumstances, GABA prevents the body from overreacting to minor stimuli, such as sudden noises.
However, when GAD65 antibodies hinder this process, the excitatory part of the nervous system will rush forward unimpeded, ultimately leading to convulsions and spasms.
Therefore, targeting B cells has become one of the main paths in the development of SPS drugs.
On July 15, 2024, Kyverna Therapeutics announced that its autologous CD19-targeted CAR-T therapy KYV-101 has been granted FDA Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of refractory SPS.
Currently, KYV-101 is undergoing Phase 2 trials in several autoimmune fields, including SPS, multiple sclerosis, and myasthenia gravis.
According to the safety expansion study, as of July 31, 2024, no serious immune effector cell-associated neurotoxicity syndrome (ICANS) or cytokine release syndrome (CRS) above grade 3 was observed in 36 autoimmune disease patients who received treatment.
Now, the treatment of SPS focuses on alleviating symptoms, including diazepam (sedative), baclofen (muscle relaxant), corticosteroids, and sometimes rituximab or plasma exchange.
The arrival of cell therapy will promote the evolution of the SPS treatment landscape. In the future, will Celine Dion benefit from this and achieve a cure?
【Editor’s note】The above content (~5000 words) is a quick translation of a Chinese article by DrugTimes team. To read the original article, please click here. All comments are warmly welcome. Many thanks!
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