The Lerner Research Institute Notations - Cleveland Clinic Lerner ...

NEUROSCIENCES$6.2 million multiple sclerosis grantPPG renewal allows continued study of inflammation, tissue injury linksThe National Institutes of Health haveawarded a $6.2 million Program ProjectGrant renewal to a team of investigators atThe Lerner Research Institute and TheMellen Center for MS Treatment andResearch to continue investigating the interplaybetween inflammation and tissue injuryin multiple sclerosis (MS).Among the research objectives are toidentify molecular mechanisms responsiblefor inflammation and neurodegeneration inMS brains, to use magnetic resonance imagingto monitor and evaluate the physicalchanges to patients' brains during the courseof the disease, and to use cDNA macroarraysto identify biomarkers of the therapeuticresponse to interferon-beta (the most widelyused treatment for MS).Richard Ransohoff, M.D., Neurosciences,serves as Program Director forresearch that involves more than 30 physicians,bench scientists, support staff, statisticiansand research technologists throughoutthe Clinic and the LRI. In addition to Dr.Ransohoff, project leaders are Bruce Trapp,Ph.D., Chair, Neurosciences; RichardRudick, M.D., Chair, Division of ClinicalResearch; and Elizabeth Fisher, Ph.D.,Biomedical Engineering.The pathology of multiple sclerosis isassociated with inflammation, scarring of themyelin (the tissue that covers and protectsnerve fibers) in the brain and spinal cord, anddegeneration of demyelinated nerve fibers.MS patients experience varying degrees ofneurological impairment depending in parton the location and extent of the scarring.MS patients in the early stage of the diseasetypically experience clearly defined flareupsand episodes of acute worsening of neurologicfunction, followed by partial or completerecovery periods. This stage of the diseaseis called relapsing-remitting MS. MostPart of LRI’s research into MS is to compare brain scans of people without MS (left)with scans of MS patients to measure brain atrophy (right).patients with relapsing-remitting diseaseeventually develop secondary-progressiveMS, in which patients steadily worsen withor without occasional flare-ups and minorrecoveries. Although MS is often describedas an autoimmune disease (one in which thebody's own immune system attacks normalbody tissue -- in this case, the cells that makemyelin), the “autoimmune hypothesis” is notcentral to the PPG-supported research program,termed “Tissue injury and inflammationin MS,” which is designed to obtain usefulinformation about how MS progresses,regardless of its underlying cause.The grant renewal allows the LRIresearch teams to continue a coordinatedresearch program initially funded in 1999.The initial program looked at three principalareas. Dr. Ransohoff investigated what signalingmight be involved to cause leukocytes(white blood cells) to invade the centralnervous system. Dr. Trapp focused on howlesions caused by the disease affect the axonalnetwork -- the long single-cell paths thatcarry signals from one nerve cell to anotheror to organs and muscles. Drs. Fisher andRudick directed their attention to relationshipsbetween conventional MRI imagesthought to show early signs of inflammationand subsequent atrophy of the brain.The LRI PPG is considered unique in itsexclusive focus on direct study of MS itself,rather than surrogate models of the disease.Part of the initial project was development ofa unique brain and spinal cord donation programin which MS patients and their familiesgave prior permission to use the materialafter the death of the patient. During the firstfive years, the studies provided tissues from36 patients, and 127 patients (including the36) have registered for the donation program.The efforts require collaborationamong the Clinic's clinical, imaging, pathologyand administrative staffs.2 Notations · Winter 2005 The Lerner Research Institute