Summaries of 50 New MS Research Projects
September 25, 2002
The National Multiple Sclerosis Society has just committed $15.4 million to support 50 new MS research projects with terms of up to five years. The new grants are part of a research program slated to invest over $32 million this year alone to advance MS research, including funding more than 300 new and ongoing MS investigations in the U.S. and abroad.
Six of the new projects stem from a firstever collaborative funding agreement with the NIH. (See pages 4-7.) These are part of the Society’s targeted research initiative to study the underexplored area of gender differences in MS.
Following are brief descriptions of the 50 newly approved MS research projects, reviewed by the National MS Society’s volunteer panels of scientific advisors or, in the case of the special gender grants, by a special advisory panel convened by the NIH.
Thanks to generous research-restricted gifts from individual donors and Research Honor Roll gifts from National MS Society chapters, we were able to make commitments to find funding support for all of these new projects. However, when research commitments are made, the money is not in hand to meet them. The Society now has over $40 million in current- and future-year commitments to meet. Money must be raised each year to fulfill them.
The new projects fall into six categories:
Seeking Better Treatments
Ultimately, the goal of the biomedical research program of the National MS Society is to develop therapies (both medications and rehabilitation programs) that will combat MS. The Society supports clinical treatment and rehabilitation trials in a number of ways: by providing full or partial financial support to investigators conducting trials; by funding parallel studies to understand how an experimental treatment may work; by participating on committees to monitor safety and ensure the quality of trials; and by training young physicians to excel in the meticulous process of MS clinical trials through our Sylvia Lawry Physician Fellowship Program. The Society’s sponsorship of basic and clinical research lays the foundation upon which most clinical trials are based.
The Society is currently supporting 26 projects testing MS therapies and rehabilitation methods, for a total financial commitment of $8.1 million. Following are summaries of five new clinical studies that investigate experimental methods of treatment and rehabilitation. Three of these new grantees are Sylvia Lawry Physician Fellows, who are receiving training and hands-on experience in designing and conducting clinical trials.
Fred D. Lublin, MD Mount Sinai Medical Center School of Medicine New York, NY Region: New York City Chapter Award: Research grant 10/1/02-9/30/05; $759,654
“Oral megadose corticosteroid therapy ofacute exacerbations in MS (OMEGA)” Amulti-center clinical trial comparing oralversus intravenous steroids to speedrecovery from acute attacks of MS.
Steroids are the most common treatment for MS relapses (acute attacks), to help speed recovery from the attack. But there is little information about the effectiveness of oral steroids compared to the commonly used intravenous route, which is inconvenient and expensive. Fred D. Lublin, MD, and colleagues in seven MS centers in New York City are studying the safety and benefit of high-dose oral versus intravenous steroids in the management of acute attacks in MS.
The study involves 140 people who have experienced an MS relapse within seven days. Participants are randomly assigned to one of two treatment groups: high-dose oral steroids and intravenous placebo for 5 days or intravenous steroids and oral placebo for 5 days. The study is double-blinded: neither examining physicians nor patients will know which active treatment is being administered.
This important clinical trial will provide valuable information about the most common treatment for MS relapses. If oral steroids are shown to be as effective as the more cumbersome and more expensive intravenous route, this may bring about a major change in the practice of medicine related to treating MS exacerbations.
Bruce C. Cree, MD, PhD University of California at San Francisco The School of Medicine San Francisco, CA Region: Northern California Chapter Award: Sylvia Lawry Physician Fellowship 8/1/02-7/31/05; $120,000
Receiving training on the proper ways toconduct clinical treatment trials in MS.
Bruce Cree, MD, PhD, is receiving training and hands-on experience in clinical trial design and implementation at a premier MS clinical center. He is involved as a physician in many clinical trials being conducted at the MS center in all forms of multiple sclerosis, and is also participating in planning new trials.
Dr. Cree is bolstering his hands-on experience with coursework in clinical trial design and epidemiology. He also is one of the attending physicians at the MS Center, and is working on a special project with the UCSF genetics team.
By the end of this fellowship, Dr. Cree should be fully trained to plan and conduct clinical trials aimed at finding better treatments for all forms of multiple sclerosis.
Susan A. Gauthier, DO Brigham and Women’s Hospital Boston, MA Region: Central New England Chapter Award: Sylvia Lawry Physician Fellowship 8/1/02-7/31/05; $120,000
Receiving training on the proper ways toconduct clinical treatment trials in MS.
Susan Gauthier, DO, is receiving training and hands-on experience in clinical trial design and implementation at a premier MS clinical center. She is involved as a physician in several clinical trials being conducted at the MS center in all forms of multiple sclerosis, and is also participating in planning new trials. Dr. Gauthier is doing coursework in clinical trial design and statistics to enhance her training.
By the end of this fellowship, Dr. Gauthier should be fully trained to plan and conduct clinical trials aimed at finding better treatments for all forms of multiple sclerosis.
Areen Said, MD University of Maryland Hospital Baltimore, MD Region: Maryland Chapter Award: Sylvia Lawry Physician Fellowship 9/1/02-7/31/05; $121,000
Receiving training on the proper ways toconduct clinical treatment trials in MS.
Areen Said, MD, is receiving training and hands-on experience in clinical trial design and implementation at a premier MS clinical center.
He is involved as a physician in several clinical trials being conducted at the MS center, and is also participating in planning new trials. Dr. Said is receiving training in MRI techniques and is using this tool in conjunction with ongoing clinical trials. He is also gaining hands-on experience caring for individuals who have MS and doing coursework in clinical trial design and statistics.
By the end of this fellowship, Dr. Said should be fully trained to plan and conduct clinical trials aimed at finding better treatments for all forms of multiple sclerosis.
Maria T. Schultheis, PhD Kessler Institute for Rehabilitation West Orange, NJ Region: Greater North Jersey Chapter Award: Research grant 10/1/02-9/30/05; $357,840
“Examining the demands of driving inmultiple sclerosis” How aspects of MSmay interfere with driving abilities, andhow to address this quality of life issue.
For many people, driving represents a key quality-of-life element. For those with MS, the ability to drive a car can be affected by a variety of symptoms – although little research to date has examined this concern.
Maria T. Schultheis, PhD, and colleagues have demonstrated that people with MS who have cognitive impairment score poorly on computerized driving tests and have more motor vehicle accidents compared with healthy controls or those with MS without cognitive impairment.
These findings underscore the importance of understanding factors related to driving ability in individuals with MS. Dr. Schultheis’s project is seeking to clarify the specific cognitive and physical demands of driving.
A total of 120 adults with MS and 30 without MS are participating. All participants are being administered comprehensive physical and cognitive assessments, as well as standardized driving evaluations. The team is comparing the groups to examine the influence of specific impairments on drivingrelated skills, and conducting analyses to identify the cognitive factors that may contribute most to driving performance in people with MS.
This unique research will provide much needed information about the demands of driving, and will help develop better ways to evaluate potential impediments. This should lead to ways to help people living with MS stay on the road safely and enjoy a more independent lifestyle.
PSYCHOSOCIAL ASPECTS OF MS
Quality of Life Issues
MS can challenge virtually every facet of a person’s life, as well as the lives of family members. Projects funded within the category of psychosocial research explore how the disease affects family life, work, cognition and emotions, and seek to address these problems to improve quality of life. The National MS Society is currently supporting 10 projects on the psychosocial aspects of MS, including the following two new grants.
Laura J. Julian, PhD University of California at San Francisco Langley Porter Psychiatric Institute San Francisco, CA Region: Northern California Chapter Award: Postdoctoral fellowship 8/1/02-7/31/05; $141,771
“Early detection of neuropsychological and psychiatric symptom in multiple sclerosis” Determining the presence of cognitive and emotional symptoms early in the course of MS, to improve their detection and treatment.
About half of those with MS experience some sort of cognitive impairment at some point during the course of their disease. It may take the form of memory loss or difficulty with problem solving and abstract thinking. In addition, many people diagnosed with MS describe symptoms of anxiety, while many others report depression.
These cognitive and affective symptoms can occur in people before MS is diagnosed, that is, in people who have “clinically isolated syndromes” (CIS) that may develop into MS. Laura J. Julian, PhD, is studying cognitive problems in individuals who present with CIS, in order to better define the nature and eventual course of these problems. She is attempting to identify early markers for further impairment – such as abnormalities that are detected by magnetic resonance imaging – that may ultimately lead to functional decline and disability in people with MS.
This research will help determine the most appropriate tools and techniques to assess cognitive and emotional status in early MS. The results also may pave the way for early, more effective treatments to address these common, debilitating symptoms.
John J. Randolph, PhD Dartmouth Medical School Lebanon, NH Region: Central New England Chapter Award: Postdoctoral fellowship 8/1/02-7/31/04; $92,344
“Functional and structural neuroimaging of executive functions in MS” Using brain imaging to examine physiological processes during thinking tasks to understand cognitive problems in MS. About half of those with MS experience impaired cognitive function at some time during their disease, even possibly in early stages. At particular risk are “executive” functions, such as planning, the use of strategy, and the ability to control one’s behavior.
Prior studies have indicated that when executive functions are impaired in people with MS, they correlate with the presence of lesions in specific areas of the brain. However, it has not been shown how the brain is activated in MS during executive tasks or if the brain compensates for these deficits, which is what John J. Randolph, PhD, seeks to demonstrate.
Using a novel imaging technique – functional magnetic resonance imaging (fMRI) – he is comparing patterns of brain activation in eight people with relapsing-remitting MS with those of eight people without MS. This form of imaging can be done while the participants are performing tasks involving executive functions. The participants are also being given a questionnaire to evaluate perceived difficulties with executive tasks. Task-related brain activation patterns are being assessed in relation to the volume and location of MS lesions.
Functional MRI provides a new window to observe active brain function. This study should add to our information about the influence of specific lesions on cognitive function and should also aid in rehabilitation of cognitive impairment in MS.
HEALTH CARE DELIVERY & POLICY
Improving Care Standards
MS can have profound effects beyond medical problems, including impacts on family life, career, standard of living and general quality of life. MS also involves special concerns for medical care: Do individuals with MS have access to quality health care and health care insurance? Access to specialists?
Investigators working under the auspices of the National MS Society’s Health Care Delivery and Policy Research Program study such issues, providing data that can serve as the basis for influencing public policy, and offering people with MS and their families practical ways for improving the quality of their lives.
With the helps of its volunteer Health Care Delivery and Policy Research Advisory Committee, the Society establishes priority areas each year and releases a request for proposals from investigators in the field. The priority areas for 2002 focus on: quality of health care in MS; and special health care needs of subgroups of persons with MS. The following two new projects responding to those priorities were recently awarded.
Marcia L. Finlayson, MSc, OTR, PhD University of Illinois at Chicago College of Applied Health Sciences Chicago, IL Region: Greater Illinois Chapter Award: Health Care Delivery & Policy Research Contract 7/1/02-6/30/05; $379,390
“Aging with multiple sclerosis: unmetneeds in the Great Lakes region”Exploring the impact of aging on personswith MS, and identifying their health andquality of life needs.
As people age, they often face a new set of medical needs. For individuals with MS, aging can be especially challenging, but little research has been done to examine the special medical needs of these individuals, and how those needs, such as assistance in getting to the doctor, are or are not met.
Marcia Finlayson, MSc, OTR, PhD, is conducting a study to explore this issue. She is focusing on a large region around the Great Lakes to draw from the experience of individuals representing geographic and demographic diversity. Dr. Finlayson is collecting information about current unmet health-related service needs using focus groups and interviews with patients, caregivers and medical professionals.
Her team will use the data gathered in this study to provide information about the medical needs of older individuals with MS and the factors that contribute to whether or not those needs are met. The results can be used to assist health care providers in working with older adults with MS, and help in developing strategies for improving health and quality of life for these individuals.
Gregory C. Pope, MS Division of Health Economics Research RTI International Waltham, MA Region: Central New England Chapter Award: Health Care Delivery & Policy Research Contract 7/1/02-6/30/05; $493,059
“Quality of health care in multiple sclerosis” Analyzing standard and recommended health care practices in persons with MS to establish a basis for improving standards of care.
Individuals with MS face any number of health care needs as their disease progresses and as symptoms develop and change over time. Receiving good health care can improve to a person’s quality of life. But what constitutes good health care for a disease like MS, which varies so much in terms of symptoms and severity?
To address this question, Gregory Pope, MS, is conducting a comprehensive study of the characteristics of health care among persons with MS. His team is examining records based on health insurance claims to create a picture of how health care is utilized and accessed by individuals with MS. The team is also examining existing guidelines for health care in MS. Using these data, the team will develop a comprehensive set of guidelines for quality health care in MS.
The goal is to establish quality indicators that can be used by health care providers, patients, insurers and organizations like the National MS Society to measure, advocate for, and achieve good medical care for all individuals who have multiple sclerosis.
NERVOUS SYSTEM REPAIR
Restoring Brain Tissues
Now that therapeutic agents are available that can at least reduce the ongoing immune assault against nervous-system tissue in some forms of MS, the idea of trying to repair the damage is no longer a mere dream. Decades of research into neurophysiology and the biology of glial cells have been laying the groundwork for finding ways to restore normal function in individuals with MS.
The Society is currently funding 13 investigations focusing on central nervous system repair, for a total commitment of $2.9 million. The following two new projects focus on identifying biological impediments that must be overcome if normal function is to be restored, and exploring natural stores of replacement cells.
Katerina Akassoglou, PhD New York University Skirball Institute - School of Medicine New York, NY Region: New York City Chapter Award: Research grant 10/1/02-9/30/05; $286,200
“Fibrin in demyelination andremyelination” Exploring whether fibrin,a molecule found in MS brain lesions, mayinhibit myelin repair, and whether itsactivity can be reversed to foster recovery.
A hallmark of MS is the loss of the material called myelin that coats nerve fibers, and the seeming inability of the body’s natural processes to repair the damage. Katerina Akassoglou, PhD, is studying the role of fibrin, a natural substance that is deposited at sites of myelin damage in MS, in both myelin damage and suppression of myelin repair in MS. She believes that fibrin may inhibit myelin repair by interfering with oligodendrocytes, the cells responsible for myelin production.
In this series of experiments, Dr. Akassoglou is investigating the effects of fibrin on oligodendrocytes and immune cells in brain tissue that contains areas of myelin damage. She is also testing whether depleting fibrin in mice with an MS-like disease can diminish tissue damage, and whether a vaccine that inhibits fibrin can promote myelin regeneration in these mice.
Understanding the role that fibrin plays in MS is a new area of research that may yield important clues about how to treat or prevent the debilitating myelin damage that occurs in this disease.
Jeffery D. Kocsis, PhD Yale University The School of Medicine West Haven, CT Region: Greater Connecticut Chapter Award: Research grant 10/1/02-9/30/06; $566,416
“Systemic delivery of bone marrow cellsto repair demyelinated spinal cord”Attempting to restore nerve-insulatingmyelin in the spinal cords of mice byinjecting stem cells from bone marrow,and testing for signs of recovery.
MS is marked by the destruction of myelin, the protective coating that surrounds nerve fibers in the central nervous system (the brain and spinal cord). A number of cell types have been tested in animal models to restore myelin in areas where it has been damaged. Recently, researchers have demonstrated the potential of cells in bone marrow (spongy tissue found in bones) to turn into myelin-forming cells when injected directly into a region of myelin loss or by injecting them into a vein.
Jeffrey D. Kocsis, PhD, has used the latter approach successfully to repair myelin on nerve fibers in the rat spinal cord. This project further extends those exciting findings.
Dr. Kocsis is injecting bone marrow cells in attempts to repair myelin damage in different rodent models. He is then measuring the extent of repair, and whether nerve fibers with repaired myelin are capable of nerve signal transmission. He is also testing whether multiple areas of myelin damage can be repaired. Although this approach is still experimental in rodent models, the prospect of using an expandable and renewable source of bone marrow cells to repair myelin in people with MS is a promising one.
Nerve Tissue Destruction
Nerve signals are transmitted through the wire-like arm of nerve cells, called the nerve fiber or axon. Any disruption to the conductive myelin that ensheathes the axon, or to the axon itself, can weaken or block these vital signals. Research from neuropathology studies indicate that the immune attack on the central nervous system in MS not only causes damage to myelin, but also to axons. Investigators are working to determine how and when axons get damaged, and how to protect them.
Among the tools investigators are using to track nerve tissue damage in MS are new magnetic imaging technologies. These include MRS, which can detect levels of specific chemicals to monitor axonal damage, and diffusion tensor imaging (DTI), a sensitive monitor of pathological changes in the brain.
The Society is currently funding 15 projects in the area of neuropathology, for a total commitment of $5.9 million. These include the following new project, focusing on possible ways to block a destructive enzyme that may play a role in MS.
Isobel A. Scarisbrick, PhD Mayo Clinic Foundation Rochester, MN Region: Minnesota Chapter Award: Research grant 10/1/02-9/30/05; $395,838
“Mechanisms of myelencephalon specificprotease-mediated proteolysis indemyelination” The role of a proteindestroyingenzyme in the destruction ofnerve-insulating myelin in MS-likedisease, and possible ways to block itsactivity.
The neurologic symptoms of MS are caused by a breakdown in myelin in the brain and spinal cord. Myelin coats and insulates nerve fibers. In previous studies, Isobel Scarisbrick, PhD, noted that levels of a natural brain enzyme called myelencephalon specific protease (MSP) are dramatically elevated in areas where myelin has been destroyed in both animals and humans with MS. This current study is aimed at revealing a possible role for MSP in the destruction of myelin in MS.
Dr. Scarisbrick is testing the idea that MSP encourages the migration of destructive cells into the nervous system. To do this, she is blocking its activity and noting any decreases in neurologic symptoms and myelin damage produced by destructive cells in mice with an MS-like disease. She is also determining whether MSP damages myelin directly by manipulating MSP levels in the mice, and correlating the amount of myelin breakdown.
Results of this research could identify MSP as a potential target for drug therapies designed to stop myelin destruction in MS.
GENETICS OF MS
While MS is not directly inherited, we know that multiple genes – out of an estimated 30,000 needed to make and maintain the human body – likely work in concert with unidentified infections or other environmental triggering factor to influence whether a person develops MS.
The National MS Society has been supporting a major genetics initiative since 1991. This entails collecting genetic material from blood samples from families with more than one member has MS. In addition, investigators are searching for DNA patterns shared by people with MS and people from specific ethnic or racial groups; studying populations with high rates of MS; and investigating known genes relevant to immune function and other aspects of the disease process. Others are searching for genetic clues to why some individuals respond to specific therapies and others do not – the emerging field of “pharmacogenetics.”
Researchers now have clues to the locations of several genes that may contribute to susceptibility to MS, but no single gene has yet been identified. Knowing the identity of these genes will bring vital clues to the actual cause of MS and ways to treat or even prevent it.
The Society is currently funding 10 major projects in the targeted area of genetic susceptibility, with current commitments of $4.7 million, including the following two new projects.
Jorge R. Oksenberg, PhD University of California at San Francisco School of Medicine San Francisco, CA Region: Northern California Chapter Award: Research grant 10/1/02-9/30/05; $714,582
“Family-based genetic studies inethnically distinct MS population”Searching for MS susceptibility genes bystudying genetic material from familieswith distinct ethnic backgrounds.
Scientists know that genes (segments of hereditary material sequenced on chromosomes that direct all the activities of a cell) influence a person’s susceptibility to MS. Pinpointing the exact location of these “MS genes” could help determine who is at risk for developing the disease, and may provide clues to its cause.
In conjunction with a team of genetics investigators at the UCSF, Jorge Oksenberg, PhD, and colleagues have screened genetic material from hundreds of families with multiple members who have MS in search of MS susceptibility genes. Now he is fine-tuning this search by collecting blood samples from a large number of ethnically diverse families who have only one member with MS. The team is focusing on ethnic groups with low, medium and high susceptibility to MS, and searching for commonalities and differences that may help pinpoint chromosome regions that contain MS genes.
These important genetic studies could lead to methods to identify people at risk for the disease and even influence the development of genetically based treatments.
Leena Peltonen, PhD University of California at Los Angeles School of Medicine Los Angeles, CA Region: Southern California Chapter Award: Research grant 10/1/02-9/30/05; $298,066
“Characterization of genetic locipredisposing to multiple sclerosis”Searching for genetic abnormalities thatmay contribute to making personssusceptible to developing MS.
MS is known to occur in people who have a genetic susceptibility to developing it. For a decade, investigators have been searching for the multiple genes that confer this susceptibility. Leena Peltonen, MD, is searching for MS susceptibility genes in the genetic material from a group of closely related families in Finland. In such a small, relatively homogenous population, these genes should be easier to find and their role in influencing MS susceptibility more easily tested. Dr. Peltonen has already identified four genes in these families that may be involved in a predisposition to MS. In this study, she is continuing to narrow down areas of interest on chromosome 5, one of the 23 pairs of ribbon-like chromosomes that contain all human genes.
By providing greater insight into the role genes play in susceptibility to MS, this study may also form the basis for the design of novel gene-based therapies for the prevention and treatment of this disease.
GLIAL CELL/MYELIN BIOLOGY
Can Myelin Be Repaired?
Recent discoveries are making the biology of glial cells an increasingly exciting area. Exploring glia, which include cells in the nervous system that make myelin, the coating that insulates and protects nerve fibers, has always been a cornerstone of MS research. Myelin, and cells that make it, appear to be the main target of the immune attack in MS.
Researchers are finding, however, that certain cells resident in our bodies may have the potential to play a role in myelin repair. Many investigators are looking at immature myelin-making cells, known as “progenitors” or “precursors,” to determine if they can be stimulated to repair myelin. Investigators working in this field are also working to identify how glial cells become targets in MS, and how they might be protected. The Society is currently funding 76 research projects in glial cell/myelin biology, for a total commitment of $18.6 million, including the following nine new projects.
Jill S. Cameron, PhD Beth Israel Deaconness Medical Center The School of Medicine Boston, MA Region: Central New England Chapter Award: Postdoctoral fellowship 9/1/02-8/31/05; $130,947
“The role of integrins in myelination”Studying molecular signals that influencethe production of nerve-insulating myelin,for clues to ways to stimulate myelinrepair in MS.
During the course of MS, myelin – the material that insulates nerve fibers – is attacked by the immune system and damaged, interrupting nerve signals. In the process, nerve fibers and oligodendrocytes, the cells that produce myelin, are also damaged.
People with the relapsing-remitting form of MS experience periods of inflammation alternating with periods of remission. During these remission periods, partial myelin repair may occur. Total repair, however, requires the presence of oligodendrocytes and intact nerve fibers, and also molecular signals within the extracellular matrix (ECM), an elaborate structure between cells that contains signaling molecules. Jill S. Cameron, PhD, is examining the role of two key molecules in the ECM, which may play a pivotal role in providing signals that stimulate myelin formation. She is doing so by studying myelin repair processes and abnormalities in mice genetically engineered to lack these molecules.
Ultimately, the findings from this work may define a new pathway that could be used as a target for therapies that promote myelin repair in people with MS.
Domna Karagogeos, PhD Foundation for Research and Technology- Hellas Heraklion, Greece Award: Research grant 10/1/02-9/30/05; $285,448
“Functional and biochemical studies ofthe juxtaparanodal adhesion protein”Exploring the properties of a protein thatappears crucial to the interaction of nervefibers and their myelin coating and propernerve signaling.
MS involves an immune attack against brain and spinal cord myelin, the sheath of fats and proteins which speeds nerve signal conduction. Myelin insulation is not continuous; rather, it is separated by unmeylinated spots called the nodes of Ranvier. The molecules surrounding these nodes are crucial for maintaining communication between nerve fibers and oligodendrocytes, the cells that make myelin. Domna Karagogeos, PhD, is investigating the role of one of these molecules, called TAG-1, in the transmission of nerve signals and communication between nerve fiber and oligodendrocyte.
Mice that have been engineered to be deficient in TAG-1 are being studied for clues to the role of TAG-1 in myelin and nerve fiber structure and function, and the extent to which TAG-1 interacts with other important nerve-signaling molecules at the nodes of Ranvier.
Deciphering the function of TAG-1 may be instrumental in understanding myelin/ nerve interactions and the myelin damage that occurs in MS, and may suggest ways to restore nerve signal transmission in tissues damaged by the disease.
Mireya Marin-Husstege, PhD UMDNJ-Robert Wood Johnson Med. Sch. Piscataway, NJ Region: Mid-Jersey Chapter Award: Advanced postdoctoral fellowship 8/1/02-7/31/05; $166,226
“Regulation of myelin components byhistone deacetylation” Understanding oneaspect of the formation of nerve-insulatingmyelin, ultimately for clues to repairingmyelin damaged in MS.
Oligodendrocytes are the cells in the brain and spinal cord that manufacture myelin, the membrane that wraps around nerve fibers and which is damaged in MS. Oligodendrocytes develop from immature cells called progenitors. At a certain point in their development, progenitors stop multiplying; the genes that control myelin production are switched on, and the progenitors “differentiate,” or take a final step to become dedicated myelin-making cells. Mireya Marin-Husstege, PhD, is searching for the trigger that activates the genes that control myelin production.
Her research suggests that oligodendrocyte differentiation is triggered when tiny proteins within the genes undergo a natural process called deacetylation, during which they lose acidic molecules. When a drug that stops deacetylation is administered, progenitors do not mature into oligodendrocytes. Dr. Marin-Husstege is studying how deacetylation affects the production of a key myelin component, called galactocerebroside, in isolated samples of oligodendrocytes as well as in rat models.
This intricate work will add to the knowledge needed to find ways to stimulate myelin repair after it is destroyed in MS.
Cecilia B. Marta, PhD University of Connecticut Health Center School of Medicine Farmington, CT Region: Greater Connecticut Chapter Award: Postdoctoral fellowship 8/1/02-7/31/05; $141,771
“MOG signaling in oligodendrocytes vialipid rafts” Examining how a proteincomponent of nerve-insulating myelinfunctions and how it might become atarget for immune attack in MS.
Myelin oligodendrocyte protein (MOG) is a relatively minor part of the myelin sheath – the material that covers nerve fibers and which is attacked in MS. However, research shows that it is at least one target of the immune attack in persons with MS, and it is also targeted in mice with the MS-like disease EAE. Furthermore, antibodies (immune proteins) against MOG destroy myelin. But destructive antibodies against myelin are not the only reason myelin is destroyed and fails to completely repair itself in MS.
To investigate other ways myelin can be disrupted, Cecilia B. Marta, PhD, is studying MOG interactions with other proteins in “lipid rafts,” which are complexes of fat-like molecules and proteins. Within these lipid rafts, signals that pass between MOG and other proteins may result in disruption of myelin formation. Dr. Marta is attempting to identify the other proteins in lipid rafts, using new technology known as “proteomics,” which enables researchers to separate and identify large numbers of proteins at once.
Findings from this work may point to strategies to prevent MOG-related damage during the initial stages of MS and encourage myelin repair.
Robin Miskimins, PhD University of South Dakota The School of Medicine Vermillion, SD Region: Dakota Chapter Award: Research grant 10/1/02-9/30/05; $415,678
“Molecular analysis of myelin basicprotein gene expression” Understandingthe genetic control of a protein in nerveinsulatingmyelin, and its function inmyelin growth and repair.
In MS, myelin – the material that protects nerve fibers – is destroyed and is not completely repaired. Any attempt to restore it or induce production of new myelin requires a thorough understanding of the molecular signals that regulate myelin formation.
That is the focus of Robin Miskimins, PhD, who is studying how the genes responsible for myelin formation are activated. She is concentrating specifically on the gene that produces MBP (myelin basic protein), a major protein component of myelin. Her previous studies have identified proteins involved in stimulating the formation of MBP. Now Dr. Miskimins is defining more precisely the pathway by which these proteins transmit information to the MBP gene. She has designed a set of experiments involving myelin- making cells in mice and in laboratory dishes to determine how these proteins interact to stimulate MBP.
Information gathered from this project will help elucidate the role of MBP in normal myelin formation, and may contribute to devising ways of stimulating myelin repair in individuals with MS.
Steven E. Pfeiffer, PhD University of Connecticut Health Center School of Medicine Farmington, CT Region: Greater Connecticut Chapter Award: Research grant 10/1/02-9/30/05; $293,845
“Mechanisms of myelin biogenesis” Usingadvanced techniques to understand andpossibly stimulate the production andrepair of nerve-insulating myelin byoligodendrocytes.
A fundamental area of MS research is investigating how the myelin membrane that surrounds nerve fibers is assembled. This basic information is needed if scientists are to find ways to stimulate the repair of myelin after it has been damaged by MS. Steven Pfeiffer, PhD, is studying how key myelin components are transported from where they are made in the central cell body of myelin making cells, called oligodendrocytes, to the distant sites of the emerging myelin membrane where they are needed if myelin is to properly insulate the nerve fiber.
Myelin components are transported within bubble-like structures called vesicles, and their movement appears to be controlled by different molecules. Dr. Pfeiffer is using a variety of sophisticated techniques to identify these molecules. Of particular interest are so-called “tethering complexes,” groups of molecules that direct the vesicles to specific sites within the growing myelin membrane, as well as small proteins called GTPases that assist in this process.
Identifying the molecules involved in the organization of the myelin sheath may lead to further research aimed at regenerating the myelin that is destroyed in MS.
Jonathan Song, PhD University of Wisconsin-Madison The School of Veterinary Medicine Madison, WI Region: Wisconsin Chapter Award: Research grant 10/1/02-9/30/05; $363,463
“Identification of oligodendrocytesubtypes” Clarifying differences insubtypes of myelin-making cells in thebrain and spinal cord, and factors thatinfluence their development and function.
Oligodendrocytes are cells that form brain and spinal cord myelin, the insulating material of nerve fibers. Two different types of these cells have previously been identified.
Type I/II oligodendrocytes make myelin for multiple nerve fibers having small diameters.
Type III/IV oligodendrocytes make myelin for nerve fibers that are fewer and larger in diameter.
These two types have different biochemical properties, and both are essential for proper myelin formation. Much is still unknown about oligodendrocytes.
For example, are Types I/II and III/IV genetically programmed to be different, or are they different because of the environments in which they develop? Jonathan Song, PhD, is seeking to answer this and other questions by isolating each type of oligodendrocyte from rats, analyzing their genetic makeup, and transplanting them into rats’ spinal cords to evaluate how they form myelin.
Another important question is whether all or just some of the different types of oligodendrocytes are damaged by MS. Dr. Song’s work may provide important information related to this question, and how that damage can be repaired.
Patricia A. Wight, PhD University of Arkansas for Medical Sciences The School of Medicine Little Rock, AR Region: Arkansas Division Award: Research grant 10/1/02-9/30/05; $359,276
“Developmental control of myelinproteolipid protein gene regulation”Exploring genetic factors that control thedevelopment of a specific protein in nerveinsulatingmyelin, for clues to stimulatingmyelin repair in MS.
Cellular blueprints known as genes control the production of all the proteins in the body, including those that make up myelin, the sheath that insulates nerve fibers and is attacked in MS. Patricia A. Wight, PhD, is studying how the gene for a particular myelin protein called proteolipid protein, or PLP, is regulated. She is focusing on a small area of the PLP gene that may constitute the “onoff switch” for PLP production.
PLP is not only made in myelinproducing cells (called oligodendrocytes) but in other cells as well, although in much smaller amounts. The degree to which PLP is produced within cells is controlled by regulatory elements within the PLP gene itself. Dr. Wight is identifying these elements and determining how they stimulate or repress the PLP gene in different cell types.
This basic research on an important component of myelin should help researchers better understand myelin production and repair and how those processes can be harnessed to reverse the damage caused by MS.
Aliya U. Zaidi, PhD Wayne State University The School of Medicine Detroit, MI Region: Michigan Chapter Award: Advanced postdoctoral fellowship 8/1/02-7/31/04; $101,003
“Oxidative-stress induced death pathwaysin oligodendrocytes” Studying biologicalmechanisms that may lead to the death ofmyelin-making cells in MS.
In MS, an immune response directed against myelin, the material that encases nerve fibers, also causes the destruction of oligodendrocytes, the cells that make myelin. Increasing evidence suggests that apoptosis, a process by which cells self-destruct, is at least one of the mechanisms behind the death of oligodendrocytes in MS. Harmful byproducts called oxidants, which can be released during the immune-mediated destruction of myelin, have been shown to stimulate apoptosis.
Aliya U. Zaidi, PhD, is exploring the possible link between oxidants and oligodendrocyte death. She is evaluating the effects of oxidants on the oligodendrocytes of several strains of mice with inbred neurological disease and determining which strains are susceptible and resistant to oxidant damage. She is also investigating the biochemical processes involved.
Finding the factors that contribute to the death and survival of oligodendrocytes may suggest therapies to prevent their loss and encourage the repair of myelin in people with MS.
Why the Immune System Goes Awry Better treatments and a cure are the ultimate goals of MS research, and perhaps no branch of investigation has borne more fruit toward these goals than the study of the immune system. All five FDA-approved therapies for MS emerged from the growing understanding of how the immune system works and how it can be manipulated to suppress or regulate immune attacks.
Researchers funded by the Society are investigating many cells and proteins in the immune system whose complex interactions can spur on or suppress the immune attack. By evaluating the importance of these components, we can find new and better ways to successfully treat MS.
The National MS Society has current, multi-year commitments of some $39 million to support 140 research projects focusing on the immunological underpinnings of MS, including the following 20 new awards.
Burkhard Becher, PhD Dartmouth Medical School Lebanon, NH Region: Central New England Chapter Award: Harry Weaver Neuroscience Scholar 8/1/02-7/31/07; $558,104
“CNS-endogenous cells in antigenpresentation, costimulation, & immuneregulation in an in vivo model of MS”Exploring the role of brain cells infacilitating the immune attack againstnervous system tissue in MS-like disease.
MS is the result of a misdirected immune attack against the myelin coating of nerve fibers in the brain and spinal cord. This attack is triggered in part when scavenger-like cells called macrophages “present” small pieces of myelin to immune cells called T cells.
Burkhard Becher, PhD, is using a new approach to look more closely at this step in the disease process. In preliminary studies, his team found that mice lacking macrophages in the brain developed fewer symptoms of an MS-like disease than normal mice. Dr. Becher has devised a method to differentiate between macrophages that reside in the brain and those that reside in other areas of the body. This method is being used to help shed light on where and how the crucial interaction between T cells and macrophages occurs. Using this system, he is tracking and analyzing the effects of various molecules implicated in working with macrophages and T cells to initiate or enhance the immune attack on myelin in MS.
These experiments may yield significant insights into the location and timing of the immune attack that triggers MS, and may also suggest new molecular targets for future MS therapies.
Melissa K. Callahan, PhD Cleveland Clinic Foundation Learner Research Insitute Cleveland, OH Region: Ohio Buckeye Chapter Award: Postdoctoral fellowship 8/1/02-7/31/05; $130,947
“Mononuclear cell chemokine receptors:In vitro studies” Using an advanced,artificial membrane to test ways to blocksignals that attract destructive immunecells into the brain and spinal cord in MS.
Early in MS, immune T cells breach the brain’s protective wall of cells lining blood vessels (the “blood-brain barrier”) and initiate an immune attack that destroys brain and spinal cord tissue. Melissa Callahan, PhD, is investigating the role of “chemokines” – small molecules that affect the movement and activation of immune cells – in T cell invasion of the brain and the subsequent nerve tissue damage that occurs in MS.
Dr. Callahan is constructing a unique model of the human blood-brain barrier and studying factors that influence T-cell migration across this artificial barrier. She is investigating chemokines and their docking proteins, or receptors, and determining which receptors on the T cell surface and which chemokines are most potent at stimulating the migration of T cells across the barrier. Several substances are in development that may be capable of blocking specific chemokine receptors and thus impeding Tcell migration. Dr. Callahan’s research could help identify those chemokine receptors that would be the best targets for such a blocking agent, which could prevent T cells from invading the brain and launching their destructive attack.
Sumone Chakravarti, PhD Brigham and Women’s Hospital Harvard Institutes of Medicine Boston, MA Region: Central New England Chapter Award: Postdoctoral fellowship 8/1/02-7/31/05; $120,382
“Effect of polymorphic forms of a Th1-specific molecule, TIM-3 on EAE”Exploring a molecule on aggressiveimmune cells which may be a potentialtarget for therapies to stop the immuneattack in MS.
MS and an experimental model of MS called EAE are caused by the reaction of T cells against the myelin sheath that insulates nerve fibers. A subset of T cells, called Th1 cells, is thought to be the key player in launching this mistaken immune attack. Sumone Chakravarti, PhD, has noted that a protein found on the surface of Th1 cells, called TIM-3, may regulate the activity of scavenger- like immune cells called macrophages that are involved in the disease process. Mice with severe EAE appear to have increased amounts of TIM-3.
Dr. Chakravarti has identified slight variations that can occur in the gene that controls TIM-3. In this project, Dr. Chakravarti is investigating these gene variations in mice that are either susceptible or resistant to EAE. She is also studying how TIM-3 influences the anti-myelin activity of Th1 cells.
Knowing the contribution of TIM-3 and other factors that trigger the T-cell attack against myelin may provide clues for developing new therapies to stop MS.
Thomas G. Forsthuber, MD, PhD Case Western Reserve University School of Medicine Cleveland, OH Region: Ohio Buckeye Chapter Award: Research grant 10/1/02-9/30/05; $178,296
“Avidity maturation of T cells in multiplesclerosis” Identifying the protein targetof immune T cells and their activity in thedevelopment of MS.
The disease process in MS is initiated by an attack launched by T cells, immune system cells that erroneously recognize substances in the central nervous system (CNS) as foreign. Among the T cells’ autoimmune targets is myelin oligodendrocyte glycoprotein (MOG), a protein that is found on the surface of myelin — the substance that insulates nerve fibers in the CNS.
Thomas G. Forsthuber, MD, PhD, and colleagues have found strong T cell responses to MOG in people with MS, and hypothesize that these responses may coincide with the onset of disease or relapses. Because it is difficult to obtain information on the specificity of T cell responses in people with MS, Dr. Forsthuber’s team is examin-
ing T cell activity in mice with EAE, an MSlike disease. They are injecting the mice with MOG, and then tracking MOG-specific T cell responses in the blood, spleen and central nervous system over the course of the disease. They are testing the idea that the T cell reaction to MOG will correspond to the onset of disease and disease relapses. These studies on MOG-specific T cell responses in the animal model will shed new light on the autoimmune attack and will lay the groundwork for understanding and treating this attack in people with MS.
Bruno Gran, MD University of Pennsylvania Philadelphia, PA Region: Greater Delaware Valley Chapter Award: Advanced postdoctoral fellowship 8/1/02-7/31/04; $105,318
“Role of IL-12 and the IL-12 receptor inthe pathogenesis of EAE” Determiningthe complex role of a key immunemessenger protein in the immune attackin MS-like disease.
The immune attack against nervous system tissue in MS is launched by immune cells, called T cells, that martial other immune forces by releasing messenger proteins called cytokines. Interleukin-12 (IL-12) is a cytokine that appears to play a major role in the immune attack in MS. In fact, an experimental treatment that blocks IL-12 is under clinical investigation for MS.
To better identify the exact mechanisms of action of this cytokine, Bruno Gran, MD, is investigating its role in mice with EAE, an MS-like disease. Dr. Gran is using a unique approach to tease out IL-12’s function in immune tissues compared to its function in the brain and spinal cord. He is also studying the role of two different components of the docking site on immune cells through which IL-12 sends its signals. Mice deficient in one component are resistant to developing EAE, while mice deficient in the other component develop more severe disease.
This work should help define the complex mechanisms by which IL-12 contributes to MS, and may hasten the development of new experimental approaches for treating it.
Jaewon Han, PhD The Scripps Research Institute La Jolla, CA Region: San Diego Area Chapter Award: Advanced postdoctoral fellowship 8/1/02-7/31/04; $101,003
“Regulation of T lymphocyte functionthrough the a4 cytoplasmic domain” Therole of a molecule on the surface ofimmune T cells in the development of MS.
MS is a disease of the central nervous system (CNS, the brain and spinal cord) that culminates in the destruction of myelin, the protective sheath on nerve fibers. This destruction is prompted by an attack by the body’s own immune system, which mistakenly recognizes myelin as a foreign invader.
In the process immune cells leave the bloodstream and migrate into the CNS. Integrins, a family of molecules found on the surface of immune T cells, are key to helping T cells move into the CNS where they generate the attack against brain and spinal cord tissues.
Jaewon Han, PhD, is focusing on one integrin, alpha 4 beta 1, to investigate how it regulates T cell movement into the CNS. He is creating cells with integrins that are altered through genetic engineering, and testing whether and how the alterations change T cell behavior. Using mouse models of MS which incorporate these genetic changes, Dr. Han is studying whether the alterations make any difference in immune cell processes, and ultimately to disease. He is attempting to show how integrins contribute to the development of MS, and how they might be altered to change the course of the disease.
The results should help us understand how T cells enter the CNS, and could lead to a novel therapeutic strategy to fight MS.
Laurie E. Harrington, PhD University of Alabama at Birmingham Birmingham, AL Region: Alabama Chapter Award: Postdoctoral fellowship 12/1/02-11/30/05; $120,382
“Defining the roles of P-and E-selectinduring CD4 T cell migration” Howspecific molecules help escort damagingimmune cells into the brain and spinalcord in MS-like disease, for insights intopreventing disease.
In MS, T cells – the immune system’s patrol cells – recognize myelin (the substance that insulates nerve fibers) as a foreign tissue to be destroyed. Normally, T cells that are reactive against “self” tissues are eliminated.
In some individuals, however, myelinreactive T cells escape this elimination process and enter the bloodstream, eventually penetrating the blood-brain barrier and launching the attack against myelin in the brain and spinal cord. The blood-brain barrier is a layer of tight cells that line blood vessels, and normally prevents most immune cells from entering the nervous system.
Laurie Harrington, PhD, is studying how T cells penetrate the blood-brain barrier, with particular focus on adhesion molecules that help destructive T cells “stick” to the blood vessels and assist in their migration across the barrier. She is examining how T cells move, in isolated cell samples as well as in mouse models, when adhesion molecules are both present and absent.
Understanding the means by which T cells infiltrate the brain and spinal cord may suggest new strategies to stop this migration and prevent the immune attack that leads to MS.
Adam P. Kohm, PhD Northwestern University Medical School Chicago, IL Region: Greater Illinois Chapter Award: Postdoctoral fellowship 9/1/02-8/31/05; $130,947
“Protective mechanisms of CD30IgG3 inrelapsing experimental EAE” Studyinghow an experimental therapy may stopthe immune attack MS-like disease, forclues to its possible use in treating MS.
In MS, immune T cells infiltrate the brain and spinal cord and launch an attack on myelin, the insulating material that encases nerve fibers. To become activated, though, T cells usually require two distinct signals. The first signal is delivered to the T cell when it encounters a “foreign” protein. In autoimmune diseases like MS, T cells incorrectly recognize the body’s own tissues as foreign, and thus the first signal is given. The second signal is delivered by other molecules that participate in the immune response: Without the second signal, T cells remain inactivated.
This two-signal dependency could prove useful in eliminating the disease-promoting potential of T cells. To test one such approach, Adam P. Kohm, PhD, has synthesized an antibody (immune protein) called CD3-IgG3 that can mimic the first signal to T cells without requiring the second signal.
This first signal is so strong that it bypasses the need for the second signal, overriding the normal autoimmune response. Dr. Kohm is testing this antibody as a treatment in mice with EAE, a model of MS. The antibody is being given at various stages of disease to see if it protects against disease progression. This study may provide insights into new strategies for stopping MS.
Shaun McColl, PhD Royal Adelaide Hospital Adelaide, Australia Award: Research grant 10/1/02-9/30/05; $285,354
“Chemokine receptors as potentialtherapeutic targets in MS” Targetingmolecules that attract immune cells intothe brain and spinal cord withexperimental therapies to stop theimmune attack in MS-like disease.
MS is an inflammatory disease of the central nervous system (CNS, the brain and spinal cord). The process of inflammation involves special molecules that recruit immune cells from the blood to the CNS. These recruitment molecules, called chemokines, are activated when they bind with docking sites, or receptors, on the surface of immune cells.
By developing compounds to inhibit chemokine receptors, Shaun McColl, PhD, hopes to block this activation and prevent inflammation and subsequent CNS damage in MS. Dr. McColl is testing five experimental compounds that inhibit chemokine receptors to identify the optimum targets, dose, route and timing of treatment, in mice with EAE, a model of MS. He is also studying the genes that control chemokines and their receptors to better understand their activity in EAE and, by extension, MS.
Based on this chemokine analysis, Dr. McColl and his team seek to identify new receptors and develop new compounds to inhibit them, and evaluate the ability of these compounds to inhibit or modify EAE.
Chemokine receptors represent valuable drug targets, and Dr. McColl’s research may lead to the development of novel therapies for MS based on these targets.
Richard A. O’Connor, PhD Trudeau Institute Saranac Lake, NY Region: Upstate New York Chapter Award: Postdoctoral fellowship 8/1/02-7/31/05; $131,854
“The mechanisms of adjuvantimmunotherapy in EAE” How doesinnoculation with an infectious agentprotect mice against MS-like disease, andhow can this be applied against MS?
MS involves an attack against tissues in the brain and spinal cord by the body’s own immune system. Immune T cells are thought to lead the attack, and other T cells produce messenger proteins, or cytokines, that normally turn off attacks. One cytokine that had been thought to worsen the immune attack is interferon gamma. However, recent research in mice infected with a bacterium called “BCG” suggests that IFN gamma released during the infection actually makes the mice resistant to developing MS-like disease.
Richard O’Connor, PhD, is working with mice infected with BCG, and other mice that have not been infected, to tease out how IFN gamma may protect the mice from MS-like disease. He suspects that IFN gamma deactivates T cells that would normally trigger the immune attack against brain and spinal cord tissue.
This work suggests that IFN gamma may have complex functions in inflammatory diseases like MS, sometimes making the disease worse, sometimes better. This novel approach may lead to ways to harness the immune system’s natural ability to shut down immune attacks to curb or event prevent MS.
Julie K. Olson, PhD Northwestern University Chicago, IL Region: Greater Illinois Chapter Award: Advanced postdoctoral fellowship 9/1/02-8/31/05; $154,745
“The role of innate immune responses in avirus-induced model of multiple sclerosis”Studying the effects that immuneresponses to viruses and bacteria have onthe development of an MS-like disease.
When a virus or bacterium enters the body, the immune system immediately swings into action. First, T cells bind to pieces of the invader, producing a cascade of immune messenger chemicals. Second, these messengers stimulate the proliferation of immune cells that eventually neutralize the invader. However, in doing so, sometimes these events also set off an “autoimmune” response against body tissues.
Julie Olson, PhD, is exploring how an immune response to a virus or bacterium could result in the autoimmune attack against brain and spinal cord tissues in MS. She is focusing on Theiler’s murine encephalomyelitis virus (TMEV), which infects the mouse nervous system and eventually causes the same kind of immune-mediated neurological damage seen in MS. She is comparing the immune responses in strains of mice that are susceptible to TMEV and those that are resistant, seeking to discover which cells are critical to inducing an immune response to a virus, and what role a similar immune response may have in the development of MS.
Information gleaned from this intricate study may suggest how MS is triggered, and potentially offer clues to its prevention and treatment.
Shalina S. Ousman, PhD The Scripps Research Institute La Jolla, CA Region: San Diego Area Chapter Award: Postdoctoral fellowship 8/1/02-7/31/05; $107,462
“Role of interferon-gamma & its signalingpathways in IL-12-induced immune diseaseof the CNS” Determining the activity andinteractions of messenger chemicals thatfacilitate the immune attack in MS andmay be suitable therapeutic targets.
In MS, the immune system launches an attack against tissues in the brain and spinal cord. Previous research has implicated an immune messenger chemical called interleukin-12 in this immune attack. Another immune messenger, interferon gamma (IFN gamma), is thought to facilitate the damaging effects of IL-12, but how these two messengers interact in MS is unknown.
To learn more, Shalina S. Ousman, PhD, is studying mice that have been genetically engineered to constantly produce IL-12 in the brain. These mice develop spontaneous disease similar to MS. The pathway that leads to IFN gamma production is known to be controlled by a molecular signal called STAT1. In these mice, Dr. Ousman is looking for molecular signals that stimulate IFN gamma activity, and analyzing neurological injury in mice that have normal and abnormal levels of such IFN gamma signaling molecules.
Unraveling the complex signals such as these, that prompt the immune system to overreact against myelin in MS, is an important step in developing better treatments to fight the disease.
Trevor Owens, PhD Montreal Neurological Institute McGill University Montreal Quebec, Canada Award: Research grant 10/1/02-9/30/05; $224,838
“Costimulation in an animal model forMS” Investigating an immune mechanismcrucial to the activation of the immuneattack in MS and MS-like disease andpossible ways to circumvent it.
Immune cells called T cells are key players in the immune attack that causes MS. One type of T cell, called CD4, has been thought to initiate the attack against nerve-insulating myelin in the brain and spinal cord – an attack that is carried out by numerous immune cells and molecules. Another type of T cell, called CD8, was until recently thought to be active later in the attack, inflicting actual damage on myelin. Trevor Owens, PhD, has found data to suggest that CD8 cells, when present in the brain, may also initiate the attack against myelin, and he is investigating whether they may play a primary role in MS.
This idea is being tested by implanting CD8 cells into the brains of mice that have been genetically engineered to produce a “co-stimulatory factor” known to prompt T cells to react against myelin. Because CD8 cells are known to act by killing other cells, Dr. Owens is examining their ability to induce MS-like disease by killing myelinmaking and nerve cells, and is also investigating the contribution of the co-stimulatory factor to the CD8-mediated disease process.
These experiments may answer important questions about the role of CD8 cells in MS and reveal potential avenues for prevention and treatment.
Thomas M. Petro, PhD University of Nebraska Medical Center College of Dentistry Lincoln, NE Region: Nebraska Chapter Award: Research grant 10/1/02-9/30/05; $209,708
“Role of IL-12 gene expression in virusinducedencephalomyelitis” Exploring thefunction of a gene that controls animmune-system messenger chemical andits possible activity in MS-like disease.
The exact mechanism underlying the immune attack in MS is still unclear, but one factor is an overproduction of certain cytokines – immune messenger proteins that participate in this attack. One cytokine, interleukin- 12 (IL-12), normally signals immune T cells to destroy virus-infected cells, but in MS, may produce negative feedback that attacks myelin, the protective sheath surrounding nerve fibers.
In order to turn off this feedback, researchers must understand first how IL-12 is produced and which genes “turn it on.” To study IL-12 and the signaling systems that activate its genes, Thomas M. Petro, PhD, is using a mouse model that develops MS-like symptoms after infection with a virus called Theiler’s murine encephalomyelitis virus (TMEV). He aims to identify the signaling systems by which the immune response to TMEV may induce IL-12 to become overly active. These should provide clues to IL-12 activity in MS, and clues to how this important cytokine can be turned off to stop the disease.
Michael K. Racke, MD University of Texas Southwestern Med.Cent. School of Medicine Dallas, TX Region: Lone Star Chapter Award: Research grant 10/1/02-9/30/06; $744,948
“T cell activation requirement inautoimmune demyelination” Exploringfactors influencing the activation ofimmune cells in MS-like disease andpossible ways to stop it in MS.
MS is a chronic disease that waxes and wanes and/or involves a progressive course of disability. The disease involves an immune attack against myelin that insulates nerve fibers in the brain and spinal cord, which is launched by immune T cells. Normally, the immune system regulates itself and can turn off an immune attack through a variety of processes. Michael K. Racke, MD, is investigating why, as the disease progresses, the immune attack in MS does not get turned off by the immune system.
In earlier studies, Dr. Racke examined the ability of T cells to “recognize” myelin and become activated against it. He observed that the T cells in people with MS tend to become activated more easily than those in unaffected individuals. Dr. Racke’s current focus is to determine whether, during the chronic course of MS, T cells become unresponsive to normal regulatory processes that can turn off the immune attack or destroy the cells.
One particular focus is whether “costimulatory molecules,” cell-surface molecules that help to activate T cells, change over time, making the T cells more prone to continue the attack against myelin. He is using blood samples from people at different stages of MS and also exploring the question in mice with an MS-like disease.
This study will add to our knowledge of the immune attack in MS, and may assist in the development of specific therapies that can stop disease progression.
Nancy H. Ruddle, PhD Yale University School of Medicine The School of Medicine New Haven, CT Region: Greater Connecticut Chapter Award: Research grant 10/1/02-9/30/06; $561,226
“CNS inflammation & antigenpresentation in MOG-induced EAE”Understanding immune-system activity inthe brain and spinal cord during thedevelopment of MS-like disease.
MOG (myelin oligodendrocyte glycoprotein) is a component of myelin, the material that encases nerve fibers and is a target of the immune attack in MS and an experimental model of MS called EAE. MOG appears to be a key target, or antigen, that immune T cells react against to initiate this attack. Antibodies are also produced that attach to MOG and may play a role in myelin damage, but that role is not yet clearly defined.
Nancy Ruddle, PhD, has developed two mouse models of MS that permit her to study the functions of T cells and antibodyproducing B cells during the initial immune attack and subsequent myelin destruction. In one model, the immune attack is predominantly T-cell based; in the other, B cells are key players. In these experiments she is focusing on the balance between T-cell and Bcell responses in MS-like disease in mice, and by implication, in MS. Both T cells and B cells are possible treatment targets in MS, and a better understanding of their roles may help researchers develop treatments to thwart the immune reaction that leads to MS.
David W. Scott, PhD American Red Cross/Holland Lab Holland Lab Derwood, MD Region: National Capital Chapter Award: Research grant 10/1/02-9/30/05; $82,500
“Gene therapy for tolerance induction inEAE as a model for MS” “Infecting”immune cells with viruses geneticallyengineered to deliver myelin proteins, inan attempt to halt the immune attack inMS-like disease.
MS is an autoimmune disease in which immune system cells inexplicably turn against one of the body’s own tissues, the nerve-insulating myelin that promotes efficient nerve conduction. David Scott, PhD, is working on an approach that may prompt immune cells to ignore myelin proteins – a process called “tolerance” – thus suppressing MS symptoms by stopping the MS-causing immune response.
Dr. Scott’s approach involves transferring the genes, or molecular blueprints, for three myelin proteins known to elicit a misdirected immune response in MS into immune cells called B cells. These B cells will then be injected into mice with EAE, a disease that resembles MS, in an attempt to divert diseasecausing immune responses and in essence, train the immune system to ignore actual myelin as a target. Dr. Scott is measuring the ability of this therapy to reduce symptoms of EAE and analyzing the mechanisms behind this gene-induced tolerance.
These experiments may lead to a novel therapeutic strategy that forces the immune system to ignore brain and spinal cord tissues to stop MS.
Jill Suttles, PhD University of Louisville Health Sciences Center Louisville, KY Region: Kentucky/SE Indiana Chapter Award: Research grant 10/1/02-9/30/05; $435,741
“Role of fatty acid binding proteins in thepathogenesis of EAE” How a moleculethat allows fatty acids to function mayplay a role in the immune attack in MSand MS-like disease and how it might beblocked.
Fatty acids, which are parts of lipids or fats, bind to docking sites inside cells known as “receptors,” and that binding sets off communication and activity within the cell. One family of receptors – called fatty acid binding proteins (FABPs) – plays an important role in regulating cell metabolism and function. Recent studies have shown that mice genetically engineered to be missing one FABP are resistant to diabetes. Jill Suttles, PhD, has found that mice engineered to be deficient in two particular FABPs are resistant to EAE, an MS-like disease in mice. Dr. Suttles is currently examining the basis for this resistance. Preliminary evidence suggests a reduced ability to spark inflammatory responses in the brain and spinal cord.
Dr. Suttles is testing this idea by injecting disease-causing immune cells into mice that lack FABP, and also testing whether inhibitors of FABP can reduce inflammation. Further investigations will look at another family of receptors called peroxisome proliferator- activated receptors (PPARs), which may also be involved in inflammation, and may be regulated by FABPs.
By investigating how fatty acid receptors are involved in inflammation in the central nervous system, this research could identify new potential targets for developing treatments to stop MS.
Biying Xu, MD, PhD American Red Cross/Holland Lab Holland Lab Derwood, MD Region: National Capital Chapter Award: Advanced postdoctoral fellowship 8/1/02-7/31/05; $148,265
“Gene therapy for tolerance toencephalitogenic proteins” Testing theeffectiveness of gene therapy -- a noveltherapeutic approach -- in an MS-likedisease in mice.
MS involves an immune attack against one or more components of myelin, the insulating coating on nerve fibers in the brain and spinal cord. MS comes in many forms, and so does its equivalent animal model, called EAE. One type of EAE in mice is a chronic, relapsing disease that involves an immune attack against a protein in myelin called myelin oligodendrocyte glycoprotein (MOG). MOG is located on the surface of the myelin sheath. Biying Xu, MD, PhD, has chosen to look at MOG as a target for altering the disease process in mice with EAE, in hopes of identifying new avenues for treating human MS.
Immune T cells that “recognize” and launch an attack against MOG play an important role in the early stages of MOGinduced EAE. Dr. Xu believes that eliminating or inactivating the MOG-specific T cells in EAE might be accomplished through gene therapy. This approach is being tested on different strains of mice with MOG-induced EAE to gauge its effectiveness in mice with different genetic backgrounds.
This study may lead to a new strategy for the treatment of MS by the novel use of gene therapy related to myelin proteins.
Habib Zaghouani, PhD University of Missouri-Columbia School of Medicine Columbia, MO Region: Gateway Area Chapter Award: Research grant 10/1/02-9/30/05; $428,258
“Down regulation of encephalitogenic Tcells” Developing a way of introducingmyelin proteins to immune cells inattempts to turn off the immune attack inMS-like disease.
In MS, T cells – normally protective cells of the immune system – launch an attack against the body itself. In both human and animal forms of the disease, T cells penetrate from the blood into the central nervous system – the brain and spinal cord. Once there, they “recognize” proteins in myelin (the sheath that protects nerve fibers) as foreign, and launch an attack that can destroy them.
What if this process could be halted early on? The ideal treatment for MS would be to devise a strategy to target and inactivate the specific T cells involved, improving or even reversing the course of the disease. Such a strategy is being tested by Habib Zaghouani, PhD, in mice with EAE, an MS-like disease. Using advanced genetic engineering tools, he is incorporating myelin proteins into immune antibody proteins, and is designing these compounds to “fool” the immune system to stimulate immune messenger proteins that can silence aggressive T cells. He is then administering these compounds to mice with EAE to see if their disease improves.
If this new approach proves successful, it will pave the way for attempting it in humans with MS.
MEASURING DISEASE ACTIVITY
Tracking the Course of MS
Research in measuring disease activity seeks to fill gaps about the course of MS and factors that may influence its course and prognosis in individuals
Multiple sclerosis can vary greatly in its symptoms and course. Although we know a great deal about the damage that occurs to tissue in the brain and spinal cord, we do not know enough about how this damage creates the symptoms of MS, and why these symptoms vary. Furthermore, no laboratory or clinical test can predict the course of this disease. Research in this category seeks to fill gaps in our knowledge about the course of MS and factors that may influence that course.
The Society is currently supporting 14 research projects, with total commitments of $3.5 million, on measuring disease activity. These include the following new project.
Joonmi Oh, PhD University of California at San Francisco The School of Medicine San Francisco, CA Region: Northern California Chapter Award: Postdoctoral fellowship 8/1/02-7/31/05; $141,771
“T2 relaxation time measurement ofspinal cord & brain for people with MS”Developing and applying new ways toanalyze imaging techniques to studyspinal cord damage in persons with MS.
Magnetic resonance imaging (MRI) uses a computer program to give a detailed picture of soft tissues of the body. Although MRI is being used to diagnose disease and monitor progression in individuals with MS, MR imaging of the spinal cord has proved to be technically difficult. Because spinal cord damage is an important contributor to disability, better techniques for MR imaging of this part of the central nervous system are urgently needed.
Joonmi Oh, PhD, is developing new imaging sequences and computer analysis protocols for the brain and spinal cord using a less commonly used MRI technique. The technique would be useful for contrasting between normal and myelin-damaged brain tissue, but is seldom used because it takes longer to acquire the necessary images. Dr. Oh is attempting to optimize the efficiency of this method by selecting the imaging areas that will yield the most clinical information, while her computer program facilitates data processing.
This study may overcome a key difficulty in MR imaging that may also be useful in measuring outcomes in clinical trials of potential MS therapies.
New MS Gender Research Projects Launched
The Society’s jointventure with NIH tosupport research ongender influences onthe immune systembrings $7.3 million ofnew funding forprojects with directrelevance to MS
The influence of gender on MS may be a powerful one. It is vital that we understand how the biology of gender exerts its influence, and for this reason, the National MS Society has targeted this as an important area of exploration.
To leverage support of this targeted initiative, last year the Society forged a first-ever collaborative funding agreement with the National Institute of Allergy and Infectious Disease. The NIAID invited the scientific community to submit research proposals on “Sex-based Differences in the Immune Response.” Of 60 proposals reviewed by a specially convened peer-review panel, 14 were approved for funding. The Society has committed to co-funding six, for a total of $3.2 million, because of their relevance to MS. NIH’s funding share for these six projects is $4.1 million. (New funding for all 14 projects totals $16.1 million from all sources.)
Michele M. Kosiewicz, PhD Health Sciences Center University of Louisville Louisville, KY Region: Kentucky/SE Indiana Chapter Award: Research grant 7/1/02-6/30/05; Total Award: $569,250 NMSS Funding Share: $247,500
“Sex-based differences in regulatory T cellresponses” Exploring whether sexhormones alter the activity of regulatorycells that can naturally dampendestructive immune responses.
Multiple sclerosis occurs more frequently in women than in men, and this is also the case for other autoimmune diseases such as lupus. Preliminary research in mice suggests that one key difference in the immune systems of males and females is the activity of naturally occurring regulatory cells capable of switching off immune attacks. Before adolescence, there appears to be no difference between the sexes regarding these regulatory cells, referred to as CD4+CD25+ regulatory T cells. After adolescence, the numbers and function of these cells appears to be reduced in females, perhaps contributing to increased vulnerability to autoimmune disease. Michele Kosiewicz, PhD, and colleagues are investigating whether sex hormones are at the root of this difference.
In a series of innovative experiments, the team is analyzing the activity of regulatory T cells in male and female mice in different life stages, including post-adolescence and during estrous cycles. The investigators are tracking whether there are differences in the way these regulatory cells interact with other immune cells, and manipulating levels of sex hormones to determine whether these alterations change the behavior of the regulatory cells.
Gaining an in-depth understanding of how regulatory T cells behave and change over time, and how they differ between the sexes, may ultimately offer new treatment opportunities for individuals with multiple sclerosis.
Halina Offner, PhD Portland VA Medical Center Oregon Health & Science University Portland, OR Region: Oregon Chapter Award: Research grant 8/1/02-7/31/06; Total Award: $1,521,560 NMSS Funding Share: $641,268
“Immunoregulatory effects of estrogen inEAE” Determining how the female sexhormone estrogen inhibits immune-systemresponses in an MS-like disease in mice.
In people with MS, there is a distinct gender bias – women develop the disease two or three times as often as men. Sex hormones may contribute to MS susceptibility by influencing the immune attack on brain and spinal cord tissues. In previous studies, Halina Offner, PhD, found that treatment with the female sex hormone estrogen reduced the severity of EAE, an MS-like disease in mice. Specifically, estrogen reduced production of TNF-alpha, an immune messenger protein known to incite inflammation.
Now, Dr. Offner and colleagues are investigating the influence of estrogen on genes that control various cells and proteins of the immune system.
In one series of experiments, the team is examining whether estrogen can still protect against EAE in mice whose immune cells are lacking specific docking sites, or receptors, for estrogen. Dr. Offner also is screening numerous genes that have been found to be important in EAE, to determine whether they are influenced by estrogen.
The studies should provide fundamental information needed if estrogen is to be developed as a potential treatment for MS.
Timothy R. Mosmann, PhD Center for Vaccine Biology & Immunology University of Rochester Rochester, NY Region: Upstate New York Chapter Award: Research grant 7/1/02-6/30/06; Total Award: $1,347,500 NMSS Funding Share: $550,000
“Bi-directional interactions betweenimmunity and pregnancy” How theimmune system is inhibited duringpregnancy so the mother can carry a“foreign” fetus, and how this may beapplied to treating autoimmune disease.
Pregnancy presents a mystery to scientists because the fetus contains half of the father’s genes, and therefore should be rejected by the mother’s immune system as being “foreign,” just as would a foreign tissue graft. But by a little-understood process, in most cases the mother’s immune system adjusts to the fetus.
Timothy R. Mosmann, PhD, is testing the idea that the mother’s strong immune responses led by T cells (the same T cells involved in the attack in MS) are inhibited during pregnancy, and that weak immune responses are allowed to occur. His team is using a mouse model to track T cell functions and interactions during pregnancy, with particular focus on how their responses are inhibited.
This innovative research should provide new information on under-explored immune mechanisms during pregnancy, and may ultimately provide new leads for turning off immune attacks in autoimmune diseases such as MS.
Howard R. Petty, PhD College of Science Wayne State University Detroit, MI Region: Michigan Chapter Award: Research grant 7/1/02-6/30/06; Total Award: $1,116,500 NMSS Funding Share: $495,000
“Mechanisms regulating neutrophil activation in pregnancy” Tracking specific immune cells during pregnancy, to understand factors that may be capable of turning off inflammation such as that involved in MS.
In women with certain autoimmune diseases, including MS, pregnancy can actually improve symptoms, especially in the second and third trimesters, possibly as a consequence of hormone changes. Researchers are exploring immune functions during pregnancy to better understand this process.
Howard R. Petty, PhD, and colleagues are comparing the activity of immune cells called neutrophils in pregnant women, nonpregnant women, and men. Neutrophils are part of the body’s first line of defense against foreign invaders, such as bacteria. They also play a role in inflammation, and are capable of damaging tissues.
Dr. Petty’s team is measuring differences in the function of neutrophils, and is exploring new information suggesting that cells of the developing fetus may produce a factor that can neutralize the activity of the mother’s harmful neutrophils. If so, and if this factor can be understood and harnessed, it could lead to the development of a drug that would turn off inflammation.
This project should increase our fundamental understanding of immune factors at work during pregnancy, a time when MS disease activity tends to lessen. This may provide the key to new treatment approaches.
Rhonda R. Voskuhl, MD Reed Neurological Research Center University of California at Los Angeles Los Angeles, CA Region: Southern California Chapter Award: Research grant 8/1/02-7/31/06; Total Award: $1,183,500 NMSS Funding Share: $495,000
“Mechanisms underlying the protectiveeffect of pregnancy doses of estrogens inEAE” Studying the effects of the sexhormone estrogen on immune-systemresponses in MS-like disease, for clues toits potential use against human MS.
Many women with MS who become pregnant experience a “holiday” from symptoms, especially during the second and third trimesters. One possible reason for this is the changes in hormone levels during pregnancy.
Rhonda R. Voskuhl, MD, has experimentally treated mice with the MS-like disease EAE, and also a small number of women with MS, with the sex hormone estrogen at levels mimicking those in later stages of pregnancy. She found benefit in EAE and evidence of safety and hints that estrogen was beneficial in women with MS (which is being pursued in further clinical trials). She is now focusing on how estrogen alters immune responses. This is vital if estrogen is to be exploited as a possible treatment for MS.
One aim of this study is to determine which of two cell-surface docking sites (receptors) for estrogen facilitates the hormone’s beneficial effects. Dr. Voskuhl’s team is also exploring how estrogen increases the production of an inflammation-fighting messenger chemical called IL-10.
Understanding the basic biological mechanisms through which estrogen alters immune responses may lead to a new treatment for individuals with MS.
Brian Weinshenker, MD Mayo Clinic and Foundation Rochester, MN Region: Minnesota Chapter Award: Research grant 9/1/02-8/31/05; Total Award: $ 1,568,556 NMSS Funding Share: $749,820 Paid in part by Thomas Maren Foundation
“Interferon gamma polymorphisms andgender bias in MS” Studying geneticvariations related to an interferon andtheir possible connection to genderdifferences in susceptiblity to MS.
MS occurs in individuals whose genetic makeup makes them susceptible to developing the disease, and the disease occurs more frequently in women than in men. Brian Weinshenker, MD, and an international team of collaborators are approaching the question of gender difference in MS by investigating differences in the genetic makeup of men and women.
Researchers around the world are searching for MS susceptibility genes using a variety of methods, including tracing gene variations, called polymorphisms, which occur more frequently in persons who have the disease. One area of possible interest is on chromosome 12, which contains genes that control a powerful immune messenger chemical called interferon (IFN) gamma. Unlike interferon betas, used to treat MS, IFN gamma has been linked to immune attacks in MS, and recent evidence suggests it is more active in women with MS than in men.
In this project, Dr. Weinshenker’s team is aiming to fine-tune the location of the IFN gamma gene and to examine variations that occur in the gene that may account for differences in MS and MS susceptibility seen between males and females.
Ultimately, this highly focused research will help us understand gender differences in MS and may add pieces to the puzzle of immune causes of MS, and the importance of interferons in both causation and treatment.?
20 New Pilot Grants Test Innovative Ideas
Over the last six months, 20 new grants were awarded through the Pilot Research Program. These projects are aimed at quickly exploring new, untested ideas and generating preliminary data needed to apply for full grant support.
Measuring MS Disease Activity
Elliot Frohman, M.D., Ph.D. “Neuroadiologic correlates & pathophysiology of internuclear ophthalmoparesis in MS” University of Texas Southwestern Medical Center, Dallas, TX $33,000; 6/1/02-5/31/03
Psychosocial Aspects of MS
Pamela Keenan, Ph.D. ABPP “Awareness of deficit in multiple sclerosis and its relation to caregiver distress” Wayne State University, Detroit, MI, $33,000; 9/1/02-8/31/03
Janet Shucard, Ph.D. “Electrophysiological measures of processing speed & working memory deficits in MS” State University of New York at Buffalo, Buffalo, NY $33,000; 9/1/02-8/31/03
Mary Hughes, M.D. “African Americans with multiple sclerosis and apoE 4 genotyping” Medical College of Georgia, Augusta, GA, $33,000; 9/1/02-8/31/03
Central Nervous System Repair
Rick Cohen, Ph.D. “Human cord blood stem cells as a potential therapeutic source of oligodendrocytes” Coriell Institute for Medical Research, Camden, NJ, $33,000; 7/1/02-6/30/03
Bruce Gold, Ph.D. “Neuroimmunophilin ligands as potential therapeutic agents for MS” Oregon Health & Science University, Portland, OR, $33,000; 5/1/02-4/30/03
Perry Fuchs, Ph.D. “Behavioral measurement of nociception in EAE” University of Texas at Arlington, Arlington, TX, $33,000; 9/1/02-8/31/03
Yuan Bo Peng, M.D., Ph.D. “Pain mechanisms in experimental autoimmune encephalomyelitis” University of Texas at Arlington, Arlington, TX, $33,000; 8/1/02-7/31/03
Glial Cell/Myelin Biology
Rashmi Bansal, Ph.D. “Study of fibroblast growth factors and their receptors on myelination in vivo” University of Connecticut Health Center, Farmington, CT, $33,000; 5/1/02-4/30/03
John Bright, Ph.D. “Gene expression associated with oligodendrocyte differentiation from stem cells in mice” Vanderbilt University, Nashville, TN, $33,000; 4/1/02-3/31/03
Franca Cambi, M.D. “PLP splicing: in vivo analysis in a mouse model” Thomas Jefferson University, Philadelphia, PA, $33,000; 4/1/02-3/31/03
Patrizia LoPresti, M.D. “The microtubule-associated proteins in adult oligodendrocyte precursor cells” Northwestern University, Evanston, IL, $33,000; 6/1/02-5/31/03
George Molloy, Ph.D. “Association of brain creatine kinase messenger RNA and protein with myelin” University of Delaware, Newark, DE, $33,000; 7/1/02-6/30/03
Charles Sanders, Ph.D. “Biophysical characterization of the CNS proteolipid protein” Vanderbilt University, Nashville, TN, $44,000; 10/1/02-9/30/03
Yulong Han, M.D. “Study of MCP-1 expression in transgenic animal models” Cleveland Clinic Foundation, Cleveland, OH, $33,000; 5/1/02-4/30/03
Samia Khoury, M.D. “Role of corticotropin releasing hormone in EAE” Brigham and Women’s Hospital, Boston, MA, $33,000; 9/1/02-8/31/03
Brett Lund, Ph.D. “ Use of dendritic cells to analyze myelin-antigen specific T cells responses in people with MS” University of Southern California, Los Angeles, CA $33,000; 7/1/02-6/30/03
Michelle McIntosh, Ph.D. “Evaluation of methotrexate-peptide conjugate in an animal model of MS” University of Kansas, Lawrence, KS, $33,000; 9/1/02-8/31/03
Jane Parnes, M.D. “Regulation of EAE severity by the B cell surface protein CD72” Stanford University, Palo Alto, CA, $33,000; 8/1/02-7/31/03
Moses Rodriguez, M.D. “Real-time in vivo staining of CNS inflammation using MRI” Mayo Clinic and Foundation, Rochester, MN, $33,000; 6/1/02-5/31/03
3 New Research Programs Launched
The National MS Society has just launched three new research programs to speed the search for a cure and enhance its ability to find answers to health policy/services questions pertinent to individuals with MS. These programs will add a minimum of $5 million to our research obligations over the next five years. The Society currently spends some $32 million annually to support MS research, and is the largest private funder of MS research in the world.
• Collaborative MS Research Center awards are aimed at stimulating creativity and interaction among investigators working within and outside MS fields, providing 5 years of flexible funding to pursue new MS collaborative goals.
• Career Transition Fellowships focus on attracting new MS researchers to the field by providing a bridge of five years of research support to help postdoctoral research fellows move into their first faculty positions.
• In addition, a new in-house health care policy research program will enable the Society to quickly respond to short-term health services and health policy research questions and needs. This program supplements the Society’s long-standing health care delivery and policy research contract program.
These new programs stem from recommendations of a recent Institute of Medicine study, which was commissioned by the National MS Society to explore whether any new ways could be found to speed its mission to end the devastating effects of MS.
2003 Priorities Set for Health Care Delivery and Policy Research
MS can have profound effects beyond medical problems, including impacts on family life, career, standard of living and general quality of life. MS also involves special concerns for medical care.
To gather data on these issues, each year the National MS Society’s volunteer Health Care Delivery and Policy Research Advisory Committee helps establish priority areas, and releases a request for proposals from investigators in the field. The priority areas for 2003 focus on quality mental health care in MS and special health care needs of subgroups of persons with MS.
Data from such studies can help the Society influence service and benefit programs in the public and private sectors, and offer people with MS and their families practical ways of improving the quality of their lives.
NMSS Web Site Now Features Vital Resource to MS Investigators
For the first time, MS researchers from around the world can go to one place on the Internet to find and download some of the most widely used clinical assessment instruments to aid them in their work. That place is the National MS Society’s Web site: www.nationalmssociety.org. (Select Research/Clinical Study Measures.)
The clinical scales gathered on the site span over half a century of research. These scales can measure a variety of functions and conditions pertinent to individuals with MS, including gait, cognition, fatigue, mobility, bowel and bladder functions, emotional status and quality of life.
The site provices descriptions of the scales and information on how they are administered. These measurement tools play an important role in helping physicians evaluate their patients, and in helping researchers assess the value of experimental therapies.
Visit the Research section of the Society’s Web site for the latest
research news, ongoing clinical trials, and progress of Society-funded
© 2002 The National Multiple Sclerosis Society