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Novel therapeutic approach in rheumatoid arthritis

autoimmune diseasecollagenprotein-protein interactionsTCRvirtual screening

Introduction

Current therapies for rheumatoid arthritis are non-selective and use anti-inflammatory and immunosuppressive drugs with significant side effects. The techniques of virtual screening have identified some molecules, pharmacologically active, able to interfere with the mechanism behind the disease thus suggesting a novel therapeutic approach.

Technical features

T cells specific for human type II collagen, one of the possible autoantigens, have a crucial role in the development of rheumatoid arthritis (RA) in the HLA-DR4 context. Protein-protein interactions between the T cell receptor (TCR) and type II collagen bound to the allele of MHC II HLA DR4, may therefore represent the target for the development of novel drugs against RA. By means of computational techniques of virtual screening a family of pharmacologically active compounds was identified, which were able to selectively interfere with the TCR/collagenII-MHC interaction. The discovered compounds open new possibilities in the treatment of RA. This procedure, based on the selective inhibition of the immune response to the autoantigen, can be applied to different autoimmune diseases, namely multiple sclerosis, myasthenia gravis, diabetes mellitus type 1.

Possible Applications

  • Development of new drugs against rheumatoid arthritis and in general against HLA-related autoimmune disorders;
  • Personalised medicine.

Advantages

  • Selectivity of therapeutic target;
  • Reduction of collateral damages which characterise current therapies;
  • Transferability of the method to a number of HLA-related autoimmune diseases;
  • Significant reduction in time and cost compared to the high-throughput screening process.