Program in Clinical and Transational Neuromuscular Research
This translational research program is focused on bridging the gap between clinical care and the basic sciences in neuromuscular disorders. The program was officially formed in October 2012 under the leadership of Dr. Richard Nowak. While the program is based within the Division of Neuromuscular Medicine, we are committed to collaboration across many disciplines, such as immunology, genetics and biochemistry. Our primary research focus has been on immune-mediated neuromuscular diseases, such as myasthenia gravis (MG) and inflammatory neuropathies and myopathies (i.e., Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), Inclusion Body Myositis). We believe that fostering close collaboration between clinicians and basic scientists is critical in successfully advancing our understanding of these disorders and translating these discoveries into clinical practice. Biomarker discovery and working to the end of patient-tailored treatment strategy development is our major overall objective.
Our program is also a part of the Muscle Study Group (MSG), which is a consortium of scientific investigators among academic and research centers committed to the cooperative planning, implementation, analysis and reporting of controlled clinical trials and of other research for muscle and other neuromuscular diseases.
Since formation of this program, we have initiated eight studies, five of which are focused on MG. Preliminary observations made by our group and others showing the benefit of B cell targeted therapy (rituximab) for MG have compelled us to explore this further [1,3]. The success of this program is highlighted by the fact that Dr. Nowak was recently awarded a 4.8 million dollar grant to conduct the first NIH-sponsored clinical trial in MG and will serve as the national Principal Investigator for the Phase 2 Trial of Rituximab in Myasthenia Gravis.
· Immunologic Markers of Myasthenia Gravis (HIC# 0911006001)
The purpose of the exploratory research study is to collect blood samples from people with myasthenia gravis (MG). Through analysis of these specimens, the researcher hope to learn more about the underlying pathophysiology of MG, as well as find unique biological markers, which could be used to develop new therapies.
· A Phase 2 Study of Rituximab in Myasthenia Gravis
The purpose of this trial is to evaluate the safety and benefit of rituximab in patients with AChR antibody positive generalized myasthenia gravis (MG). This is a prospective, randomized, double-blind, placebo-controlled, multi-center study sponsored by the National Institutes of Health (NIH). The study will be completed within the NeuroNEXT clinical trials network.
· Efficacy of Prednisone in the Treatment of Ocular Myasthenia: The EPITOME Study (HIC# 1211011140)
The purpose of this study is to determine if prednisone is an effective therapy for newly diagnosed ocular myasthenia gravis (OMG) patients, in addition to pyridostigmine. This is a randomized, double-blind, placebo controlled study.
· Immunologic Biomarkers in theEfficacy of Prednisone in the Treatment of Ocular Myasthenia: The IB-EPITOME Study (HIC#1302011501)
This is an ancillary biomarker study for the EPITOME study. Subjects participating in the EPITOME study can also enroll in IB-EPITOME. The purpose of this study is to explore how treatment modifies the immunopathology of ocular myasthenia gravis and to identify markers of disease activity.
· A Phase 3 Trial of Eculizumab in Refractory Generalized Myasthenia Gravis
The purpose of this trial is to evaluate the safety and efficacy of eculizumab in patients with refractory generalized myasthenia gravis. This is a prospective, randomized, double-blind, placebo-controlled, multi-center study sponsored by Alexion Pharmaceuticals. The study will be conducted at approximately 100 centers worldwide.
· Immunologic Mechanisms of Inclusion Body Myositis (IBM) (HIC# 0911006001)
The purpose of the exploratory research study is to collect blood samples from people with inclusion body myositis (IBM). Through analysis of these specimens, the researchers hope to learn more about the underlying pathophysiology of IBM, as well as find unique biological markers, which could be used to guide treatment strategies.
· The International Guillain-Barré syndrome Outcome Study (IGOS) (HIC# 1302011440)
IGOS is a worldwide prospective study, conducted by the Inflammatory Neuropathy Consortium (INC), that aims to define biomarkers for disease activity and recovery and to develop prognostic models to predict the clinical course and outcome in individual patients with Guillain-Barré syndrome (GBS). The study will enroll 1000 subjects from over 100 centers.
· Immunologic Markers of Immune Mediated Neuropathies (HIC# 0911006001)
The purpose of the exploratory research study is to collect blood samples from people with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Through analysis of these specimens, the researchers hope to learn more about the underlying pathophysiology of CIDP/MMN, as well as find unique biological markers, which could be used to develop new therapies and guide treatment strategies.
1. Keung B, Robeson KR, DiCapua DB, Rosen JB, O’Connor KC, Goldstein JM, Nowak RJ. Long-term Benefit of Rituximab in MuSK Autoantibody Positive Myasthenia Gravis Patients. J Neurol Neurosurg Psychiatry. 2013, June; doi:10.1136.
2. Ray A, Amato AA, Bradshaw EM, DiCapua DB, Felice K, Goldstein JM, Lundberg I, Nowak RJ, Ploegh HL, Spooner E, Wu Q, Willis SN, O’Connor KC. Autoantibodies Produced at the Site of Tissue Damage Provide Evidence for Humoral Autoimmunity in Inclusion Body Myositis. PLoS One. 2012; 7(10): e46709.
3. Nowak RJ, DiCapua DB, Zebardast, N, Goldstein JM. Response of Patients with Refractory Myasthenia Gravis to Rituximab: A Retrospective Study. Therapeutic Advances in Neurological Disorders. 2011, Sept; 4(5): 259-266.
For any questions regarding our program, interest in participating in one of our trials or collaboration opportunities please contact the program director, Dr. Richard Nowak (email@example.com), or Hong Vu (firstname.lastname@example.org) or Joan Nye (email@example.com).
To support our ongoing efforts please join our team and make a gift toward neuromuscular research please contact Sharon McManus (firstname.lastname@example.org).