Collaborative MS Research Center Award
Peter A. Calabresi, MD
Johns Hopkins University
|Katherine Conant , MD|
John W. Griffin, MD
David N. Irani, MD
Richard T. Johnson, MD
Douglas A. Kerr, MD, PhD
Sanjay C. Keswani, MBBS
Justin C. McArthur, MBBS, MPH
Avindra Nath, MD
Carlos Pardo-Villamizar , MD
John Hopkins University, Baltimore, MD
To define how axons, the long arm of nerve cells, are damaged in MS and search for ways to protect them. Ultimately the group aims to identify new therapeutic approaches that will slow or stop disease progression.
In MS, damage to axons likely begins even during the early stage of the disease, and is a major cause of disease progression and disability. However, we do not understand if axonal injury occurs secondary to damage to myelin, the coating that insulates axons, or if it is a primary consequence of the immune attack on the brain and spinal cord underlying MS. This lack of understanding has precluded the development of effective strategies to protect nerve cells in MS.
Therefore, the primary goal of this collaborative program is to define mechanisms that underlie axonal injury in MS and to develop novel therapeutic approaches that diminish disease progression. In order to achieve this goal, Peter A. Calabresi, MD, has brought together both established and developing scientists—many of whom have expertise in other diseases where nerves are damaged—to focus on this damage as it occurs in MS. Dr. Calabresi has a long-standing interest in defining features of the immune attack in MS, and as a Center collaborator is applying that expertise to understanding the immune mechanisms that may underlie axonal injury both in cells in the laboratory and in rodent models. Avindra Nath, MD, has made important contributions to the field of human immunodeficiency virus (HIV)-induced nerve damage, and now is using a sophisticated method of examining how human nerve cells, myelin-making cells and immune cells interact in laboratory dishes, possibly causing axonal injury.
Another collaborator, John W. Griffin, MD, has expertise in nerve damage that occurs in the peripheral nervous system—outside the brain and spinal cord. He is studying rodent models of myelin damage to understand how this damage may affect axons.
These investigators are drawing on the experience of Douglas A. Kerr, MD, PhD, and David N. Irani, MD, who have worked extensively with animal models in which myelin damage is induced by immune responses to viruses and other agents. They are now translating their findings to models more similar to MS. Also on the team is Sanjay C. Keswani, MBBS, a junior faculty member who is evaluating an agent, erythropoeitin, that has shown effectiveness in battling inflammation in the MS-like disease EAE, and may have neuroprotective properties as well.
These studies are necessary precursors to conducting clinical trials of such therapies in people with MS. To assist the translation of this laboratory research to clinical trials, Justin C. McArthur, MBBS, MPH, has joined the team. Dr. McArthur has extensive experience in conducting studies of neuroprotective compounds, and has established the infrastructure to design, conduct and analyze clinical trials, including a team of imaging experts, cognitive scientists, a statistician, and other knowledgable staff.
Acting as a consultant to this project is Richard T. Johnson, MD, who is internationally known for his knowledge and expertise in infectious and immune-mediated disorders of the nervous system, including MS. Other collaborators include Dr. Pardo-Villamizar, a pathologist who studies MS brain tissues, and Dr. Conant, a molecular biologist who studies the signaling pathways inside nerve cells that are involved in how nerve
This project promises to further define the mechanisms of damage to nerve cells in MS, and identify neuroprotective strategies that will allow improved treatment of people with this devastating disease.