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

Abstract

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.