Laboratory for Myasthenia Gravis Research

The Laboratory for Myasthenia Gravis (MG) Research is dedicated to “a world without MG.” To achieve that goal the Laboratory has a broad-based research program dedicated to understanding the pathogenesis of MG with a focus on development of new therapeutics. Our therapy development program spans pre-clinical programs, clinical trials, and biomarker discovery. We work closely with the clinicians of the GW Medical Faculty Associates Myasthenia Gravis Center and investigators across the United States and the world in academics and industry.

Linda L. Kusner, Ph.D. directs the laboratory and is Associate Professor of Pharmacology and Physiology. She has been a close collaborator of Dr. Kaminski’s for many years. Their complementary expertise in appreciation of the inadequacy of present therapies and the challenges in linking animal to human studies makes for a powerful team in therapeutic development.

Brief Laboratory History

Dr. Kaminski began his career in evaluating the reasons for the preferential involvement of eye muscles by myasthenia gravis. This focused set of evaluations led to the surprising discover of low levels of naturally occurring complement inhibitors in eye muscles. Complement is the prime driver of muscle injury in MG. These observations led to a series of investigations of complement and its potential for therapeutic intervention. The laboratory performed critical evaluations of the complement system in the pathogenesis of MG in laboratory animals, including an antibody directed against the C5 component of complement. The results justified the first clinical trial by the Alexion Corporation of a complement inhibitor (Eculizumab) in humans. Eculizumab is known under investigation in a Phase 3 trial for MG.

Dr. Kaminski is part of the leadership team of the National Institutes of Health (NINDS) funded trial of thymectomy for MG.  He organized collection of thymus and blood samples from study participants which now is the largest biorepository for MG. Preliminary studies using these samples supported through supplemental funds by the NINDS are providing novel insights into MG pathogenesis.

Dr. Kusner is interested in mechanisms that lead to the persistence of autoreactive cells and inhibition of the complement system to moderate disease severity.  Her extensive knowledge in animal models of MG have led to her leadership in development of standards in performance of preclinical research in myasthenia gravis.

Focused Research Studies

Anti-apoptotic Mechanisms in Myasthenia Gravis

Along with colleagues at Roswell Park Cancer Center, Dr. Kusner discovered the novel expression an anti-apoptotic protein, survivin, in lymphocytes of patients with MG and laboratory animals.

Targeted Complement Inhibition

The laboratory has been issued a U.S. patent for development of a complement inhibitor which has led to establishment of ARC Biotechnology, LLC. The company will take the technology into further development. The expectation is that this therapy will rapidly reduce symptoms without the systemic complications of complement inhibition.

Improvement in Pre-clinical Assessment

In order to develop therapeutics, the rigor of performance and accuracy of animal models of disease must be optimized. To address the state of pre-clinical assessments for MG, the National Institute of Neurological Disorders and Stroke, Myasthenia Gravis Foundation of America, and the George Washington University sponsored the workshop, Standards of Pre-clinical Efficacy in Experimental Myasthenia Gravis on September 24th-25th, 2014 in Rockville, MD. The event brought together leaders in the field of animal evaluation for MG as well as external participants who provided unique insights into pre-clinical design. A summary of the work performed at the conference was summarized in a special issue of Experimental Neurology August 2015. Dr. Kusner continues to work with colleagues across the globe to optimized animal models of MG. 

Collaborative Research

Drs. Kusner and Kaminski work with several large and small pharmaceutical companies in consultation or active assessments of potential drugs for MG.


Contact

If you are interested in research positions in the laboratory please contact Drs. Kaminski (hkaminski@mfa.gwu.edu) or Kusner (lkusner@gwu.edu). If you are a patient, please visit the GW Medical Faculty Associates at gwdocs.com/neurology for information regarding the clinical arm of the Laboratory for Myasthenia Gravis Research and to arrange an appointment with Dr. Kaminski.


Recent Publications

Alshaikh JT, Amdur R, Sidawy A, Trachiotis G, Kaminski HJ. Analysis of a national surgical database for myasthenia gravis patients undergoing thymectomy. Muscle Nerve 2016;53:370-4.

Xie Y, Meng Y, Li H-F, Hong Y, Zhu X, Sun L, Yue Y-X, Gao X, Li Y, Wang S, Kusner LL, Kaminski HJ. GR gene polymorphism is associated with inter-subject variability in response to glucocorticoids in patients with myasthenia gravis. Europ J Neurol 2016;23:1372-9.

Kaminski HJ. Seronegative myasthenia: A vanishing disorder? JAMA Neurology 2016;73:1055-6.

Wolfe GI, Kaminski HJ, Inmaculada B. Aban IB, Minisman G. Hui-Chien Kuo H-C., …. Vincent A, Dias-Tosta E, Robin Conwit R, Odenkirchen J, Marx A, Sonett, JR, Jaretzki A, Newsom-Davis J, Cutter GR, MGTX Study Group. Randomized Trial of Thymectomy for Myasthenia Gravis. New Engl J Med 2016;375:511-522.

Xie Y, Li H-F, Jiang B, Li Y, Kaminski HJ, Kusner LL. Plasma IL-17 levels stratify across myasthenia gravis patient subtypes. Cytokines (in press).

Alshaikh JT, Amdur R, Sidawy A, Trachiotis G, Kaminski HJ. Analysis of a national surgical database for myasthenia gravis patients undergoing thymectomy. Muscle Nerve (in press).

Burns TM, Sanders DB, Kaminski HJ, Wolfe GI, Narayanswami P. Two steps forward one step back; Mycophenolate mofetil use for myasthenia gravis in the United States. Muscle Nerve 2015;51: 635-37.

Renton AE, Pliner HA, Provenzano C, Evoli A…Kaminski HJ…Drachman DB, Traynor BJ. A genome wide association study of myasthenia gravis. JAMA Neurol 2015;72:396-404.

Kusner LL, Losen M, Vincent A, Lindstrom J, Tzartos S, Lazaridis K, Martinez-Martinez P. Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model — Recommendations for methods and experimental designs. Exp Neurology 2015;270:3-10.

Losen M, Martinez-Martinez P, Molenaar PC, Lazaridis K, Tzartos S, Brenner T, Duan RS, Luo J, Lindstrom J, Kusner L. Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors--Recommendations for methods and experimental designs. Exp Neurol. 2015;270:18-28.

Punga AR, Kaminski HJ, Richman DP, Benatar M. How clinical trials of myasthenia gravis can inform preclinical drug development. Exp Neurology 2015;270:78-81.

Kusner LL, Kaminski HJ. Special issue on standardization of preclinical evaluation of animal models for myasthenia gravis. Exp Neurology 2015;270:1-2.

Drachman D, Kaminski HJ. The neuromuscular junction as Achilles’ heel: Yet another autoantibody? Neurology 2014; 82:1942-43.

Zhou Y, Kaminski HJ, Gong B, Cheng G, Feuerman JM, Kusner LL. Gene Expression Analysis of Differential Muscle Involvement by Antibody-Induced Experimentally Acquired Myasthenia Gravis. Invest Ophthalmol Vis Sci 2014; 55:4348-59.

Kusner LL, Marx A, Kaminski HJ, Fenstermaker RA, Ciesielski MJ. Survivin as a therapeutic target for antibody-mediated autoimmunity. PLOS ONE 2014;9:e102231.

Li Y, Tu Z, Quin S, Fung J, Kusner L, Kaminski HJ, Lu L, Lin F. Myeloid derived suppressor cells as therapy for experimental myasthenia gravis J Immunol 2014;193:2127-34.

Sengupta M, Cheema A, Kaminski HJ, Kusner LL. Metabolomic response to corticosteroid treatment among patients with myasthenia gravis. PLOS ONE  2014;9:e102635