Limited Benefits Halt Enrollment in Hematopoietic Stem Cell Transplantation Trialfor Stiff-Person Syndrome Should There Be More to Come?

摘要

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. 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.