Multiple Sclerosis

Anne H. Cross, MD — Section Head

 

Multiple Sclerosis (MS) is a disease that attacks primarily the white matter of the central nervous system (the brain and spinal cord). It also not infrequently attacks the gray matter as well. The disease is believed to be autoimmune. It is very common, striking around 1 in a thousand people in the US. MS can cause a wide variety of symptoms which vary from patient to patient. The past 20 years have seen great improvements in the diagnosis of the disease and its treatment. Recent breakthroughs in treatments have revolutionized care of people with MS. In the early 1990s, for the first time, medications were found that decreased MS attack rates and slowed progression of disability.

The MS neurologists at Washington University are on the cutting edge of new therapies and new imaging techniques. We have been involved in the development of many of the drugs used for treatment now, and newer drugs still under investigation. We also have been developing new diagnostic and prognostic techniques using newer imaging methods.

Facilities

Barnes-Jewish Hospital at Washington University provides comprehensive services with an inpatient neurology division, neurologic intensive care, rehabilitation facilities, home health, subacute care, extended care, home medical equipment and out patient care. We see outpatients at the Center for Advanced Medicine and at the NeuroClinical Research Unit in the McMillan Building. Barnes-Jewish Hospital and the Dept. of Neurology at Washington University have each been rated among the top ten in the nation for many years.

The John L. Trotter MS Center at Barnes-Jewish Hospital also recognizes its responsibility to provide for the medically indigent, a long standing tradition at Barnes-Jewish Hospital. The MS Clinic is supervised by MS Center faculty neurologists and staffed by Barnes-Jewish Hospital resident physicians. This clinic is held in the NeuroClinical Research Unit.

Therapies for MS

There are 4 basic approaches to therapy in MS:

  •    Shorten exacerbations and expedite the return to a remission.
  •    Prevent future worsening
  •    Provide symptomatic relief for the disabilities caused by MS
  •    Repair damage and restore the nervous system

 

Treatments aimed at the underlying disease process to prevent future worsening are available for the most common types of MS and are being researched in clinical trials for other types of MS. These include beta-interferons, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl fumarate and alemtuzumab. The MS specialists at the John L. Trotter MS Center have experience using all of these medications. In addition, we are doing research on new medications that are not yet FDA-approved that appear extremely promising, such as ocrelizumab and anti-LINGO-1.

Treatments to relieve symptoms are very valuable to the MS patient, even if they may not directly alter the underlying disease process. Our multidisciplinary team strives to improve the quality of life of our patients. Symptomatic treatments, for example, can help pain, stiffness, gait problems, tremor, fatigue, depression, memory loss, sexual function, bowel function and bladder function. . Moreover, we are actively engaged in research on several exciting new medications that relieve symptoms and improve nervous system functioning in MS patients.

Research

The cause of MS is unknown. MS appears to be caused by a complex pathologic process involving the impaired regulation of the immune system that may be triggered by a yet unknown environment or infectious agent in people with a genetic propensity. White blood cells, including lymphocytes, monocytes, and plasma cells, enter the central nervous system (brain, spinal cord, optic nerves) and ultimately cause destruction of myelin. Myelin is a protective and supportive covering of projections of nerve cells that are called axons. When myelin is damaged, conduction of nerve impulses is impaired, leading to problems with motor skills, sensory perceptions, coordination or other functions. In many cases, not only is the myelin destroyed or injured, but the axons are also destroyed. In some cases axons are completely destroyed, and this may be the cause of severe disability. The exact types of impairments depend upon the location of the damage and the extent of the damage.

Research at the John L. Trotter MS Center ranges from the study of DNA and RNA to using mouse models of human demyelinating diseases, to research on human cells and tissues to clinical trials of new therapies. Clinical trials ongoing at the John L. Trotter MS Center include several that are testing new drugs, or different formulations of older drugs, whereas others involve studies to improve imaging of the central nervous system in MS patients.

Some of the agents that have been tested in recent clinical trials at the MS Center include rituximab, vitamin D, estriol, , fampridine, anti-LINGO, and ocrelizumab. The studies we are doing are continually changing as we complete some studies and begin others.

Ongoing laboratory studies are directed toward uncovering the mechanisms that underlie the development of MS. At present, we are studying antibodies to myelin in the blood and spinal fluid, endogenous immune suppressors, the mechanisms by which certain immune cell types (such as B lymphocytes, dendritic cells, monocyte/macrophages and microglia) lead to autoimmune demyelination, newly recognized immune molecules involved in cell activation, adipokines (cytokines made by fat tissues), and several other promising leads. Our hope is that some of these research studies may result in better understanding of the MS disease process to uncover future therapies.

A large 5 year PO1 grant was awarded in Sept 2008 by the NINDS of the National Institutes of Health to Drs. Cross and Naismith and collaborators Drs. Sheng-Kwei “Victor” Song, Robyn S. Klein, John Russell, Peng Sun, Laura Piccio and others to investigate ways to determine pathology of MS lesions using diffusion tensor imaging (a type of MRI) in living patients and in the animal models. That PO1 was renewed for a second five years. We continue to attempt to find imaging methods to non-invasively understand neuropathology of MS and related diseases (such as transverse myelitis, optic neuritis, and neuromyelitis optica).

Regulation of the inflammatory response by altering diet and calorie intake is being examined by Dr. Laura Piccio and Dr. Cross. Together, they are working on how to harness and utilize endogenous regulators called “adipokines.”

Dr. Piccio and her laboratory were amongst the first to focus on an immune receptor called TREM2, which is expressed on the surface of microglia in the central nervous system. She is known internationally for her work to uncover the role of TREM2 in MS and other CNS diseases.

Dr. Wu runs a basic research laboratory focused on uncovering the cellular causes of MS. His goals include examining novel ways to modulate the immune system to lessen the damaging effects of activated immune cells in MS

The John L. Trotter MS Center continues to work to identify specific components of myelin that are targeted by the immune system. This line of research was originated at the Center by our founder, Dr. John Lee Trotter (1943-2001).

Clinical Trials