Essentially all research that may help us learn how to stop disease activity ultimately requires a better understanding of the role that the immune system plays in MS. This system is involved both in the inflammatory attacks on myelin and, very possibly, in the axonal injury that appears to contribute to longer-term disability. This includes studies on
- components of the immune system such as T cells, B cells, and antibodies
- understanding why women are affected by MS more than twice as often as men
- determining whether differences in disease pattern hold a key to better therapies
- identification of new targets for therapeutic intervention; and the identification of substances that are involved in producing axonal injury.
We especially need to know more about the molecules that the immune system uses to attack the nervous system, because each of these serves as a potential therapeutic target for new therapies, with the aim of treating the disease while leaving the rest of the immune system capable of fighting infections. Researchers are also identifying the body’s natural immune messenger molecules that dampen abnormal immune activity and that may therefore be used as therapies, as well as developing “decoys” to waylay attacking immune cells.
We’re making progress – for example:
- Deeper understanding of destructive and protective immune factors is opening up new opportunities for targeting specific sites along the immune attack pathway to turn off the attack or to protect brain tissues.
- There is a new understanding of the role of immune B cells, and at least one experimental therapy (rituxumab) that targets them
- Trials of oral therapies are underway
- Attempts are being made to block only immune cells that recognize myelin, leaving the rest of the protective immune system intact.
A few examples of the immunology studies recently funded by the National MS Society:
The MS Lesion Project
Because a treatment that helps a person with one MS lesion pattern may not help someone with a different pattern, the MS Lesion Project was designed to determine whether specific characteristics of lesions—areas of brain tissue in which myelin has been lost—will reveal why people experience the disease so differently. The goals of the MS Lesion Project are to better understand these patterns and to find ways to tell the difference among them with non-invasive tools such as MRI.
Immune System Function and Searching for New Therapies
- Lawrence Steinman, MD (Stanford University) and others participating in his Collaborative MS Research Center are using novel technology to study the immune attack in MS on a broad scale to identify targets for therapies.
- Benjamin M. Segal, MD (University of Rochester Medical Center, Rochester, NY) and colleagues at his Collaborative MS Research Center are developing therapeutic vaccines and novel immune-modulating agents to improve the treatment of MS and advance nervous tissue repair.
- No drug is as yet approved for the treatment of primary-progressive MS, and questions remain as to whether this type of MS might be an entirely different disease, rather than a variant of relapsing-remitting MS. Investigators at the University of Texas Southwestern Medical Center are analyzing blood samples from individuals with primary-progressive and relapsing-remitting MS. The investigators aim to shed light on the immune forces at work during the course of these various types of MS and how they may differ, including how they differ in their response to therapy.
Cellular and Molecular Components of the Immune Response in MS
- Researchers at the University of Maryland Biotech Institute are attempting to design a drug that will stop T cells of the immune system from recognizing and attacking myelin. This work is the result of very sophisticated studies of the 3-dimensional structure of myelin-reactive and virus-reactive T cell receptors using X-ray crystallography techniques.
- Researchers at the Mayo Clinic are investigating the possible role in axonal injury of a molecule called perforin, which is secreted by cells of the immune system and perforates the outer skins or membranes of “foreign” or virus-infected cells, causing them to die. In mice with an MS-like disease, the axons of those that lack the gene for perforin remain uninjured. Identifying mediators of axonal injury, as perforin appears to be, may lead to therapies that will prevent such injury in people with MS
- B cells, a major component of the immune system, make antibodies that may play a key role in the development of MS. Investigators at Washington University in St Louis are testing the safety and preliminary measures of efficacy of rituximab, a drug that depletes B cells from the immune system, when used in combination with existing therapies in people with relapsing-remitting MS. All participants have taken interferon beta or glatiramer acetate but continue to demonstrate MS disease activity. They will continue to take these medications while receiving rituximab by infusion. MRI scans taken before and after treatment will be compared to assess the drug’s impact on the number and size of MS brain lesions. If combining rituximab with other drugs proves to be safe and shows possible signs of benefit, a larger trial will be warranted. Larger-scale studies of the drug alone are already underway, including a trial in people with primary-progressive MS.
Download summaries of other recently funded projects focusing on the role of the immune system in MS (PDF).