Stiff-Person Syndrome

What is stiff-person syndrome ?

Stiff-person syndrome (SPS) is a rare immune-mediated disorder of the central nervous system that is characterized by rigidity and painful muscle spasms.^1-3

The condition gradually worsens and, left untreated, can lead to permanent disability^1,4 and, in some cases, death.⁵ Classic SPS, which is associated with anti-glutamic acid decarboxylase (GAD) antibodies, is the most common type of SPS and is present in 70% to 80% of people with SPS.

Where it strikes

Stiff-person syndrome affects twice as many women as men. Stiff person syndrome is typically diagnosed in people:
– between ages 30 to 50
– who have other autoimmune diseases, specifically others involving GAD65 antibodies, most commonly diabetes.⁶

Current treatments

Treatments for SPS help to control symptoms by slowing down the activation of neurons, including those that control muscles, to help reduce rigidity and spasms caused by the disease.^5,6 Additionally, immunotherapies attempt to address the cause of the disease and have also shown some benefits in treating SPS.^7-9 Despite availability of these treatments, response to treatment varies and there is currently no cure for SPS.¹⁰

CAR T-cell therapy for stiff-person syndrome

CAR T-cell therapy involves modifying a patient’s T cells to recognize and deplete cells expressing the protein targeted by the CAR in the patient’s body. Kyverna’s CD19 CAR T-cell therapy, KYV-101, specifically targets CD19, a protein expressed on the surface of B cells, which is involved in various types of autoimmune diseases. We believe our approach may present a significant advantage over current standard-of-care therapies by aiming to directly deplete B cells and potentially resetting disease-contributing B cells.

1. Dalakas MC. Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology. Neurol Neuroimmunol Neuroinflamm. 2023;10(3). doi: 10.1212/NXI.0000000000200109.
2. .Muranova A, et al. Stiff Person Syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, [cited 2024 Apr 03]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK573078/.
3. Rizzi M, et al. Long-lived plasma cells and memory B cells produce pathogenic anti-GAD65 autoantibodies in Stiff Person Syndrome. PLoS One. 2010;5(5):e10838. doi: 10.1371/journal.pone.0010838
4. Levy LM, et al. The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid. Ann Intern Med. 1999;131(7):522-30. doi: 10.7326/0003-4819-131-7-199910050-00008.
5. Duddy ME, et al. Stiff person syndrome. Front Neurol Neurosci. 2009;26:147-65. doi: 10.1159/000212375.
6. https://www.columbiadoctors.org/news/stiff-person-syndrome-not-what-you-think-it Accessed October 2024
7. Dalakas MC, et al. A double-blind, placebo-controlled study of rituximab in patients with stiff person syndrome. Ann Neurol. 2017;82(2):271-7. doi: 10.1002/ana.25002.
8. Fekete R, et al. Childhood stiff-person syndrome improved with rituximab. Case Rep Neurol. 2012;4(2):92-6. doi: 10.1159/000339446.
9. Qureshi A, et al. Stiff person syndrome (SPS) complicated by respiratory failure: successful treatment with rituximab. J Neurol. 2012;259(1):180-1. doi: 10.1007/s00415‑011‑6123‑9
10. Baizabal-Carvallo JF, et al. Stiff-person syndrome: insights into a complex autoimmune disorder. J Neurol Neurosurg Psychiatry. 2015;86(8):840-8. doi: 10.1136/jnnp-2014-309201..