UB Dept of NeurologyUBMD Neurology/JNI
brains&GAINSNovember 2, 20139-12 a.m.Center For Tomorrow
http://ubnjacobsneuro.wordpress.com/home/
@wolfegil
https://www.facebook.com/UBMDNeurology
Gil I. Wolfe, MD• Irvin and Rosemary Smith Professor and Chair since Jan 2012• 9 new Dept. of Neurology faculty
– 3 stroke– 1 multiple sclerosis– 1 adult epilepsy– 1 child neurology– 1 neurocritical care– 2 neuroimaging (100% research)
• Clinical and investigative career in neuromuscular medicine– Myasthenia Gravis (MG)
• ECU-MG-301: Double-blind, placebo –controlled trial of eculizimab in refractory generalized MG
• Clinical chair of international, NIH supported study of thymectomy in MG– Peripheral Neuropathy
• GBS longitudinal follow-up study (IGOS)– Others
• INSIGHTS– IV immunoglobulin usage patterns across U.S.
Aging, Alzheimer’s Disease & Memory
• Kinga Szigeti, MD, PhD– Director, Memory Disorders Program
Disease Classification
NMJ
Muscle
Axon
Myelin
Motor neuron
Neuronopathies& NeuropathiesALS, PLS, SMA, diabetic neuropathy, toxic neuropathy, GBS,CMT
MyopathiesMuscular dystrophy,polymyositis, dermatomyositis, IBM
Neuromuscular Junction DisordersMG, botulism
Eculizimab in MG
• Monoclonal antibody that binds complement C5, preventing cleavage to C5a
• Complement activation is key component to damage of muscle membrane in MG– Cobra venom blocks complement and prevents
induction of experimental autoimmune MG (EAMG)– Membrane attack complex (MAC) present on muscle
membrane in EAMG animals and MG patients• Up to 10% of MG patients refractory
MG and complement-mediated injury
Shiraishi et al. Ann Neurol 2005;57:289 (biceps biopsies)
Control AChRAb
MuSKAb MuSKAb
Phase II Study of Eculizimab• n=14 (30-72 yrs)• AChRAb+ and failed 2
immunosuppressives, including prednisone, for ≥ 1 yr
• No IVIg for 8 weeks or plasma exchange for 12 weeks
• Results– Reduction by >3 QMG points
during eculizimab vs. placebo marginally significant (p=0.0577)
• Side effects– Mild to moderate– Nausea, back pain, headache,
pharyngitis – 3 serious adverse advents on both
active and placebo treatment
Howard JF et al. Muscle Nerve 2013;48:76--84
600 mg IV qwk for 4 wks900 mg IV at 5th q2wks for 12 wks
ECU-MG-301: Eculizimab in refractory generalized MG
• Phase 3, randomized (1:1), double-blinded, placebo-controlled trial– Treatment duration 26 wks
• AChRAb+, age ≥ 18 yrs• MG-ADL score ≥ 6
– MG-ADL is the primary outcome measure– QMG, MGC, QOL also measured
• Failed ≥2 immunotherapies for at least 1 yr– No IVIg or PE within 4 wks– Can continue on current immunosuppressive treatments
without dose changes