Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is characterized by progressive paralysis. Two types of histological lesion are associated with MS — acute lesions, which are characterized by inflammation, and chronic 'silent' ones that show scarring and demyelination. By doing microarray analysis on human biopsy samples, Lock and colleagues show, for the first time, that there are transcriptional differences between MS-associated lesions. Using a mouse model of MS, the authors also validate some of these differentially expressed molecules as potential therapeutic targets.

In the first study, Lock et al. compared transcripts from the two lesion types and showed differential gene expression between them, uncovering several genes not previously thought to be important in MS. Comparing tissues from individuals with and without MS revealed genes whose expression was increased in MS samples, among them were the immune response molecules, major histocompatibility complex class II and immunoglobulin G; complement molecules; B-cell and macrophage-specific molecules; adhesion molecules, integrin β4 and P-selectin; and several pro-inflammatory cytokines. Expression of neuron-associated genes and those encoding proteins associated with myelin production was decreased, suggesting that the capacity for tissue repair is compromised in MS patients.

Some of these differentially regulated gene products were chosen by the authors to test in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, as potential therapeutic targets. The first study revealed that the immunoglobulin Fcγ receptor was upregulated in chronic lesions. Satisfyingly, the authors saw that Fcγ-receptor-knockout mice, in which EAE was induced, had less severe acute disease and no chronic disease, compared to wild-type mice with EAE. The first study also showed that granulocyte-colony-stimulating factor (G-CSF) was upregulated in acute lesions. The authors showed that early treatment of EAE mice with G-CSF decreased the severity of the disease but that later treatment had no effect, suggesting that G-CSF might be a regulatory molecule that naturally suppresses acute attacks.

Although EAE is a useful model for MS, clinical trials have shown that many efficacious therapies in the mouse have not worked in humans. Therefore, caution must be exercised in spite of the validation in mice of the two reported MS targets. However, this study does provide proof of principle for using microarray technology to identify new therapeutic targets. Databanks that contain large microarray data sets generated by these types of study will allow more meaningful cross-data-set comparisons to get the most out of the increasing numbers of such analyses.