Cytokines are the effective therapeutic target for RA. Is there any effective enzyme based therapeutic target which has been studied in in vivo models?
Thi is a recent review on eicosanoid enzymes targeting in RA.
Nat Rev Rheumatol. 2014 Apr;10(4):229-41. doi: 10.1038/nrrheum.2014.1. Epub 2014 Feb 11.
Persisting eicosanoid pathways in rheumatic diseases.
Korotkova M, Jakobsson PJ.
In Rheumatoid arthritis there is inflammation in the body parts. So, for targeting the disease you should target enzymes responsible for inflammation. like Cox, Lox, and enzymes responsible for the synthesis of various cytokines.
Low dose oral methotrexate with folinic acid supplements reduces gastroinestinal side effects in the treatment of RA, so presumably dihydrofolate reductase is the enzyme target in immune cells. Where the selectivity comes from would be an interesting research question.
Thank you Dr.Alan
Its a nice comment and good information also about DHFR as therapeutic target for RA..
An interesting area of research is the potential of inhibitors of proteinases as treatment in rheumatoid Arthritis (RA).
Matrix metalloproteinases (MMP) and A Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTSs) are enzymes implicated in the destruction of tissues in rheumatoid arthritis, by degrading extracellular matrix macromolecules.
Although they are involved in tissue repair, they become a part of the destructive disease process due to overexpression.
Inhibition of these enzymes by modulating gene expression or preventing protein activation can be considered for the treatment of RA.
MMPs 2,3,7,10,11,12,14,15,19,25 genes are upregulated in Collagen Induced Arthritis (CIA) in rats, which is the animal model for RA. But MMP3 seems to be the major enzyme produced by fibroblasts and macrophages in RA synovial fluid. It is also a predictor of joint destruction in RA. So this is one of the prospective targets for research.
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