Stiff Person Syndrome (SPS) is a rare, progressive autoimmune and neurological disorder. It causes muscle stiffness and painful spasms, affecting the central nervous system and increasing sensitivity to stimuli. SPS may be caused by the immune system attacking glutamic acid decarboxylase (GAD), a protein essential for the neurotransmitter GABA which helps regulate motor neurons. Although there is no cure, treatments aim to manage symptoms and target the autoimmune response.
Standard Therapies for SPS
Treatment is personalized and involves symptomatic relief and immunotherapy.
- Symptomatic Treatment: Benzodiazepines like diazepam and muscle relaxants like baclofen are commonly used to reduce stiffness and spasms by enhancing GABA effects.
- Immunotherapy: Therapies modulate the immune system. Intravenous immunoglobulin (IVIg), which provides antibodies from healthy donors, is a widely supported option for reducing stiffness and improving balance. Other treatments include plasmapheresis, corticosteroids, and immunosuppressants, though effectiveness varies.
What is the New Drug for Stiff Person Syndrome? The Rise of Cell Therapies
The most promising advancements are in cell-based immunotherapies, which aim to reset the immune system.
KYV-101: A Promising CAR T-cell Therapy
KYV-101, a CAR T-cell therapy, has been cleared by the FDA for investigation in SPS patients and is in late-stage clinical trials. This therapy modifies a patient's T-cells to target and eliminate B-cells involved in autoimmune activity. Early data from other autoimmune diseases suggests KYV-101 has a tolerable safety profile and shows promising clinical activity. The KYSA-8 trial is specifically evaluating KYV-101 for SPS.
ADI-001: Allogeneic Gamma Delta T Cell Therapy
ADI-001 from Adicet Bio is another significant development. The FDA cleared an IND amendment in late 2024 to evaluate ADI-001 in a Phase 1 SPS trial. This therapy uses allogeneic gamma delta T cells. Enrollment for the SPS group was expected to begin in early 2025, with initial data from a broader study anticipated in the first half of 2025.
Comparison of SPS Therapies
| Therapy Class | Specific Example(s) | Mechanism of Action | Status for SPS |
|---|---|---|---|
| GABA Agonists | Diazepam, Baclofen | Enhances GABAergic inhibition to reduce muscle activity | Standard Symptomatic Care |
| Immunoglobulin | IVIg | Modulates the body's autoimmune response | Preferred Immunotherapy |
| B-cell Depletion | Rituximab | Monoclonal antibody that depletes CD20+ B-cells | Investigational/Second-Line (Efficacy debated) |
| CAR T-cell Therapy | KYV-101 | Genetically modified T-cells target and deplete CD19-positive B-cells | Investigational (In late-stage clinical trials) |
| Gamma Delta T-cell Therapy | ADI-001 | Allogeneic T-cell therapy targeting autoimmune cells | Investigational (In Phase 1 clinical trials) |
The Role of Other Investigational Drugs
Research continues into other immunotherapies:
- Rituximab: This B-cell-depleting therapy has been used for SPS, but its efficacy is debated. While a systematic review noted efficacy in many patients, a large controlled trial did not show significant benefit over placebo.
- Other Biologics: Investigational therapies include FcRn inhibitors, which break down antibodies, and IL-6 receptor antagonists, which target inflammation.
Conclusion
SPS treatment is advancing, with a focus on targeted immunotherapies. While traditional medications manage daily symptoms, cell therapies like KYV-101 and ADI-001 represent the frontier of research, offering hope to reset the autoimmune process. Their progress in clinical trials is a significant development for patients with this rare condition.
For more information, you can visit the National Institute of Neurological Disorders and Stroke (NINDS).
