Epigenetic therapeutics in autoimmune disease.
Several lines of evidence suggest the involvement of disturbance in epigenetic processes in autoimmune disease. Most noteworthy is the global DNA hypomethylation seen in lupus. Epigenetic states in difference from genetic lesions are potentially reversible and hence candidates for pharmacological intervention. Potential targets for drug development are histone modification and DNA methylating and demethylating enzymes. The most advanced set of drugs in clinical development are histone deacetylase (HDAC) inhibitors. However, the prevalence of DNA hypomethylation in lupus suggests that we should shift our attention from HDAC inhibitors to DNA demethylation inhibitors. MBD2 was recently proposed to be involved in demethylation in T cells in lupus and is, therefore, a candidate target. Although this field is at its infancy, it carries great promise.
Szyf
Moshe
M
Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, QC, H3G 1Y6, Canada. moshe.szyf@mcgill.ca
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019175:DNA Methylation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D012436:S-Adenosylmethionine / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; C489325:MBD2 protein, human; D012436:S-Adenosylmethionine