1. brains&GAINS November 2, 2013 9-12 a.m. Center For Tomorrow
UB Dept of Neurology
UBMD Neurology/JNI
@wolfegil

2. 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.

3. Aging, Alzheimer’s Disease & Memory
Kinga Szigeti, MD, PhD
Director, Memory Disorders Program

4. Disease Classification
Motor neuron
Neuronopathies
& Neuropathies
ALS, PLS, SMA,
diabetic neuropathy,
toxic neuropathy, GBS,
CMT
Axon
Myelin
Neuromuscular
Junction Disorders
MG, botulism
NMJ
Myopathies
Muscular dystrophy,
polymyositis,
dermatomyositis, IBM
Muscle

5. 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

6. MG and complement-mediated injury
Control
AChRAb
MuSKAb
MuSKAb
Shiraishi et al. Ann Neurol 2005;57:289 (biceps biopsies)

7. 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 wks
900 mg IV at 5th q2wks for 12 wks

8. 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