Limited Benefits Halt Enrollment in Hematopoietic Stem Cell Transplantation Trial for Stiff-Person Syndrome

Stiff-person syndrome (SPS) is an autoimmune disease characterized by stiffness of truncal and proximal limb muscles due to co-contracture of agonist and antagonist muscles resulting in hyperlordosis, difficulty bending, slow gait, and statue-like appearance; episodic spasms precipitated by unexpected auditory, tactile, visual, or stressful stimuli; and task-specific phobias.^1,2 High-titer autoantibodies against glutamic acid decarboxylase (GAD)–65, the rate-limiting enzyme for GABA synthesis, or glycine receptors are detected in most patients, denoting impaired inhibitory neurotransmission causing excitotoxicity, spasms, and stiffness.^1–3 High GAD titers are also seen, or overlap with, autoimmune epilepsy, encephalitis, cerebellar ataxia, and myoclonus, forming the GAD spectrum disorder.^2,3 SPS responds to GABA-enhancing drugs (diazepam, baclofen, anticonvulsants) and certain immunotherapies.^1–4 A placebo-controlled trial with IV immunoglobulin (IVIg) showed significant improvements in 70% of patients,⁵ but a randomized controlled trial with rituximab did not reach significance due to strong placebo effect, although 35% of patients improved.⁶ Plasmapheresis, corticosteroids, and immunosuppressants variably show limited benefits.^2–4 Patients poorly responding to these therapies may become permanently impaired, requiring walkers or wheelchairs. Additional immunotherapies are therefore welcome.