This study was presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Dusseldorf, Germany, on Sept. 11, 2009, and found that two genes in mice were associated with good central nervous system repair in multiple sclerosis (MS). This early research holds promise for new therapies and better prediction of patient outcomes.
Allan Bieber, Ph.D., a Mayo Clinic neuroscientist and author of the study explains: “Most MS genetic studies have looked at disease susceptibility — or why some people get MS and others do not. This study asked, among those who have MS, why do some do well with the disease while others do poorly, and what might be the genetic determinants of this difference in outcome.”
According to Dr. Bieber, the research suggests that there may be a small number of strong genetic determinants for central nervous system repair following demyelinating disease, rather than a larger number of weak determinants.
Abstract
Clinical experience with humans who have multiple sclerosis and work with animal models of demyelinating disease, has demonstrated that significant CNS repair can occur after demyelination even without therapeutic intervention. However, for reasons that are poorly understood, repair often fails or is incomplete. Recently we have investigated the genetic regulation of CNS repair and remyelination in the Theiler’s murine encephalomyelitis virus (TMEV) model of demyelinating disease. We have found marked differences in spontaneous repair in different strains of mice ranging from minimal repair and the progressive accumulation of neurologic deficits in B10.Q mice, to extensive spontaneous myelin repair with axonal and functional preservation in FVB mice. The “reparative phenotype” of the FVB strain is inherited as a dominant trait in outcrosses with the non-repairing B10.Q strain. To better understand the molecular mechanisms of endogenous CNS repair, we have mapped genetic loci that are responsible for the reparative phenotype. Using single nucleotide polymorphisms (SNPs) as genetic markers, we have detected two very strong quantitative trait loci (QTLs) for CNS repair, one on chromosomes 3 (LOD~15) and one on chromosome 9 (LOD~21). The mouse genes for epidermal growth factor (EGF), a key regulator of cell growth and development, and Tyk 2, a janus kinase that plays a central role in controlling the TH1 immune response, present themselves as potential candidate genes for the QTLs on chromosomes 3 and 9 respectively. We have identified polymorphisms between the FVB and B10.Q strains in the protein coding sequences of both EGF and Tyk2 which support their roles as candidate genes. Relatively little is known about the genetics of CNS repair and these studies begin to identify the molecular pathways that are central to this poorly understood process.
Authors
Kanitta Suwansrinon, MD; Allan J. Bieber, PhD; Moses Rodriguez, MD all from Mayo Clinic
Multiple Sclerosis Treatment at Mayo Clinic
Multiple Sclerosis Research at Mayo Clinic
