Young Investigators

It is vitally important to our mission that we fund unique and inspiring multiple sclerosis studies that overstep basic science, yet still fit into the goals of what we are trying to accomplish with the chance of changing the face of MS. With that we present to you our new program that furthers MS research by using smaller grants to fund unconventional studies.

Summary of Current Young Investigators Multiple Sclerosis Studies

Kevin C. O’Connor, PhD
Assistant Professor of Neurology Yale School of Medicine

Antigen-antibody complexes in MS
Much of the attack against the brain and spinal cord tissues in MS is led by the immune system. Among the cells participating in this assault are B cells. B cells have receptors (antibodies) or docking sites on their surfaces, which bind to proteins and other biological components. B cells recognize these components (termed antigens) as foreign (non-self) through the binding of antibodies on their surface. This binding stimulates the B cell to begin secreting antibodies that bind the antigens marking them for immune mediated destruction. Although this process may be occurring in MS central nervous system (CNS) lesions, many of the details remain unknown.

Our group has isolated B cells from MS autopsy tissue and recapitulated the antibodies they make. We have used these resurrected antibodies to search for their antigen targets among MS CNS components. We have currently identified such an antigen and are continuing this endeavor. In our current work we are evaluating if these newly identified antibody-antigen pairs can be found in the cerebrospinal fluid and blood. If they are we will correlate their presence with clinical parameters in an effort to identify new biomarkers for MS. We are equally focused on understanding the role these antibodies play in the destruction of tissue in the MS CNS. Here we are using animal models of the human disease to evaluate the effect of these human antibodies on disease initiation and progress.

The overall study aim is to provide insight into the nature of the autoimmune cell response in MS, which may lead to new ways to prevent or treat the disease.

Christian von Büdingen, MD
Assistant Professor of Neurology University of California-San Francisco

The role of antibodies in MS
One of the greatest challenges in multiple sclerosis (MS) research is the unavailability of patients’ brain tissue for laboratory research. Fortunately, very recent scientific advances have shown that stem cells, called induced pluripotent stem (iPS) cells, can be derived from patients’ skin cells. These iPS cells give us the opportunity to generate our patients’ brain cells in the laboratory. iPS cell-derived brain cells can, in turn, be used to study the relevance of immune system components (e.g. antibodies) in MS. Antibodies are soluble proteins produced by highly specialized immune cells called B cells.

Several lines of strong evidence ascribe antibodies an important role in the formation of scars in brain tissue of MS patients. The proposed research project will, therefore, study the influence of MS antibodies on iPS cell-derived brain cells from MS patients.

The overall goal is to unequivocally establish the disease-relevant role played by antibodies in MS. Such knowledge is expected to greatly enhance our understanding of MS and will likely facilitate the development of innovative therapies.

Jack Ratchford, MD,
Assistant Professor of Neurology, Johns Hopkins University, Baltimore, MD Johns Hopkins University, Baltimore, MD

Optical Coherence Tomography Biomarker of Axonal Itegrity in MS
Current MS treatments are partially successful at targeting the inflammation that occurs in MS, but it has been difficult to prevent the axonal degeneration that causes much of the disability in progressive MS. Identification of neuroprotective treatments is critically important, but testing of potential neuroprotectants has been limited by a lack of biomarkers of axonal integrity. Optical coherence tomography (OCT) may be a good biomarker for measuring axonal damage in MS patients and could help to accelerate testing of neuroprotective compounds. The overall study aim will help establish OCT as a surrogate outcome measure in MS and will lead to a proposal to test several potential neuroprotectants using OCT together with traditional disability outcomes in progressive MS.