Omar Khan, M.D., professor and chair of the Wayne State University School of Medicine Department of Neurology, was awarded $1.2 million three-year investigator-initiated grant by Novartis Pharmaceuticals to study myelin tissue injury and regeneration in the central nervous system in patients with multiple sclerosis.
"We now have the capability to examine microscopic tissue injury in the brain and spinal cord in-vivo, not visible to the naked eye," said Dr. Khan, also director of the Sastry Foundation Advanced Imaging Laboratory. "Significant injury occurs in the brain in multiple sclerosis in areas that otherwise appear to be normal, but in reality are metabolically-stressed regions at risk of injury, that eventually appear as lesions on routine clinical scans."
The multi-year study to be conducted at the Wayne State University Multiple Sclerosis Center will see patients with the relapsing-remitting form of multiple sclerosis undergo high-field, multi-modal brain and spinal cord magnetic resonance imaging scans annually. The scans will include sequences that will allow examination of metabolic and structural integrity of tissue, as well regeneration of myelin tissue before and after institution of therapy.
The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white regions are where the neurons send their axons - similar to electrical cables carrying messages - to communicate with other neurons or muscles.
The white parts of the brain are white because a cell type called oligodendrocytes makes a cholesterol-rich membrane called myelin that coats the axons. The myelin's function is to insulate the axons, analogous to the plastic coating on an electrical cable. The myelin's insulation properties speed communication along axons and make that communication much more reliable. However, in patients with MS, the immune system attacks the myelin sheathing coating axons. The subsequent degradation leads to messages from the brain to other parts of the body leaking and derailing from their intended receiver.
The Wayne State University Multiple Sclerosis Center and the Sastry Foundation Advanced Imaging Laboratory are among a handful of cutting-edge imaging centers with the capability of advanced MRI imaging in live patients with multiple sclerosis and other neurological disorders.
"This is a highly complex but unique study that will include diffusion tensor imaging, magnetic resonance spectroscopy, magnetic resonance transfer ratio, cortical surface mapping and 3D sequences that will allow detailed regional analysis, along with segmentation of gray and white matter," Dr. Khan said. "Another unique aspect of the study is the examination of spinal cord, which has been challenging in the past."
Dr. Khan also said the department is fortunate to have recruited Navid Seraji-Bozorgzad, M.D., assistant professor of neurology and associate director of the Sastry Foundation Advanced Imaging Laboratory. "An excellent neurologist, Dr. Seraji-Bozorgzad is also an expert in MR imaging and computer sciences. He will develop statistical models to examine the complex relationship between visible and invisible microscopic tissue injury. Remyelination is key to recovery and functional improvement in patients with multiple sclerosis."
"I am excited to be a co-investigator in this study that provides a unique opportunity to study voxel-wise MTR analysis to determine the extent of myelin tissue repair in the brain," Dr. Seraji-Bozorgzad said. "Within each lesion in the brain in patients with multiple sclerosis, repair occurs heterogeneously. Parts of a lesion may repair completely, leaving some parts vulnerable to further injury and irreversible tissue loss. This also provides opportunity to stratify patients at risk of greater injury and design treatment strategies accordingly. In this study, we will examine the effect of a small molecule that binds to sphingosin-1-phosphate receptors in the central nervous system. Also, known as fingolimod, this is the first oral disease-modifying therapy for multiple sclerosis approved by the Food and Drug Administration."
The Wayne State University Multiple Sclerosis Center is considered among the five largest MS centers in the country, along with University of California, San Francisco, Brigham and Women's Hospital, Harvard Medical School, Cleveland Clinic and University of Texas Southwestern, Dallas. With almost 5,000 patients, the center attracts patients from all over Michigan, neighboring states and from Canada.