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Initiative on Genetics of MS

Although MS is not directly inherited, many genes appear to contribute to determining a person’s susceptibility to developing MS.  Identifying these genes and understanding how they contribute to the disease process will provide clues to the cause of MS, and perhaps ways to treat and even prevent it.

In mid-2003, the National MS Society’s Research Programs Advisory Committee reviewed the 5-year history of our targeted research effort in genetics and noted the significant increase in numbers of supported projects, the renewed interest in collaboration among research groups, and the interest of other funding agencies, such as the NIH, in MS genetics. Recognizing that MS genetics will continue to be a vital part of the Society’s investigator-initiated research portfolio, the Committee suggested that the field had matured and was self-sustaining. The Society will continue to support and promote MS genetics research through its traditional research and training support mechanisms.

Progress made in this field is summarized below.

Background
Genetic studies related to MS have been underway for many years. Patterns of transmission suggest that the disease is not a simple, single-mutation problem, but very complex, involving many genes.

By the 1990s, technology related to genomics changed radically and it became possible to undertake a whole genome analysis, searching for genetic “hot spots” that might appear more in individuals with diseases, compared to individuals without those diseases. The Society initiated a whole genome screen for MS, under the direction of Dr. Stephen Hauser at the University of California, San Francisco. New knowledge of genome screen studies, the complexities of MS genetics and the promise that new information could bring to understanding this disease underscored genetics to be an area ripe for additional funding and research, and in 1998 genetic studies became the second MS research area to be formally targeted by the Society. 

The Society worked to identify genetic researchers in countries around the world who were interested in pursuing MS genetics and who had access to populations where MS was prevalent and there was little or no migration or gene pool mixture. It was thought in that such relatively homogenous populations, MS genetics might be less complex. Groups were identified in Tasmania, Australia, and Western Finland, and grants were awarded.

Two large-scale genetics projects of particular note are the Society’s MS DNA bank, run by Dr. Hauser, which collects DNA samples from individuals with MS and their family members and shares them with researchers around the world who are seeking genetic clues to the cause of MS; and the Palmer Collaborative MS Research Center Award: MS Targeted Haplotype Project, being spearheaded by Harvard’s Dr. David Hafler, taking a new, technology-driven approach to find MS genes.

Funding Results
Through 2003, 17 projects in MS genetics were supported, ranging from molecular genetic analyses, to exploration of candidate genes, to detailed analyses of unusual families with large numbers of MS cases. The number of ongoing projects in MS genetics in 2003 was triple that from a decade previously, accounting for some 4% of total Society expenditures in 2003. A total of $6.4 million of new targeted genetics funds were allocated between 1998 and 2003. 

Since the launch of the Research Challenge of Champions Campaign, 17 new projects in MS genetics have been supported, with a total commitment of $6.4 million. Eight of the investigators attracted by this initiative had never before been grantees of the Society.

Scientific Progress
The Society’s initiative on genetic susceptibility focused significant, worldwide scientific attention to the search for the genetic underpinnings of MS, and created a platform for applying the latest, rapidly developing technology to MS research, including data from the Human Genome Project and the use of MS as a model for finding multiple disease susceptibility genes using haplotype mapping. Here is a sample of this progress:

  • Dr. Stephen Hauser’s (University of California, San Francisco) team has established a repository of genetic and clinical materials. Over 3698 DNA samples have been shared with 14 laboratories nationwide and all over the world, including the U.S., Australia, France, and Scotland. Recently, the team tested 7 of the most promising regions identified by previous research in genetic material from families in the U.S. and France, and narrowed down three areas on chromosomes 1, 3 and 19 that warrant further exploration.

  • Trevor Kilpatrick, MBBS, PhD (University of Melbourne, Australia) collected data from more than 182 Tasmanians with MS and 1,223 family members, and identified segments of HLA genes (genes that control how the immune system identifies its own tissues) in this population that may contribute to susceptibility to MS. 

  • Leena Peltonen, MD (University of Helsinki, Finland and University of California at Los Angeles) identified four genes in Finnish families that may be involved in a predisposition to MS, and her team continues to pursue these leads.

  • Brian Weinshenker, MD (Mayo Clinic and Foundation) confirmed previous studies that associated susceptibility to MS with the gene for CTLA4 a “co-stimulatory” molecule on the surface of immune cells thought to determine whether or not an immune response occurs. He also reported that variations in the gene for the immune protein IL-4 may be related to MS susceptibility and severity.

  • Jorge R. Oksenberg, PhD (University of California at San Francisco) and colleagues have been screening genetic material from ethnically diverse families who have only one member with MS. The team is focusing on ethnic groups with low susceptibility to MS (such as Asians), medium susceptibility (such as African-Americans) and high susceptibility (such as Caucasians of Northern European descent), and searching for commonalities and differences that may help pinpoint chromosome regions that contain MS genes. Among their findings thus far is an association with MS and a specific component of the immune-related HLA genes in African-Americans with MS.

  • The Society and NIH sponsored a meeting in September 2003 that gathered virtually all MS genetics groups worldwide; strategies were discussed for taking advantage of new technologies that may speed the hunt for MS genes.

Last updated August 3, 2005

 

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