May 03, 2002
Symptoms specific to two different stages of autoimmune encephalomyelitis, a murine model of multiple sclerosis (MS), are alleviated with therapy targeted to genes upregulated during each stage, investigators report.
Dr. Lawrence Steinman, of Stanford University in California, and associates conducted microarray analysis of MS lesions obtained from four patients postmortem. Thirty-nine genes were increased by at least twofold and 49 were decreased in all four samples, compared with tissue from two control subjects, they note in the May issue of Nature Medicine.
Upregulated genes included those for immunoglobulins, complement, and pro-inflammatory cytokines. In addition, genes related to pregnancy proteins and others associated with stress responses in neurodegeneration were elevated. Neuron-associated genes and genes associated with myelin production were underexpressed.
Genes were differentially transcribed in acute lesions associated with inflammation and edema and in "silent" lesions associated with gliosis and demyelination. Dr. Steinman's team investigated one gene uniquely associated with increased expression in each type of lesion.
The gene encoding granulocyte-colony stimulating factor (G-CSF) was upregulated 13-fold in acute MS lesions. Treating mice with G-CSF before symptoms appeared delayed and decreased the severity of the early stages of the disease.
In chronic silent lesions, the gene encoding the immunoglobulin Fc receptor was elevated almost eightfold. Mice lacking the Fc receptor gene experienced less severe symptoms of acute encephalopathy, and signs of chronic disease remained absent.
In an accompanying editorial, Drs. Stephen M. Tompkins and Stephen D. Miller, from Northwestern University Medical School in Chicago, comment, "This is the first description supporting molecular differences in the two types of lesions, and provides data that could ultimately influence the choice of treatment for acute versus chronic stages of the disease."
Nat Med 2002;8:451-453,500-508.
© 2002 Reuters Ltd