Histone Deacetylase Inhibitors: New Hope for Rheumatoid Arthritis?

Q.   Y.   Choo; P.   C.   Ho; H.   S.   Lin

doi:10.2174/138161208784007699

Abstract

Histone deacetylase (HDAC) inhibitors are a new family of anti-cancer agents currently undergoing clinical investigations for various oncology indications. Their anti-inflammatory activities had been well documented and they appear to be potential therapeutic strategies for various inflammatory diseases. In this review, the anti-inflammatory activities of HDAC inhibitors with emphasis on their potential applications in rheumatoid arthritis (RA) will be summarized. The possible anti-rheumatic mechanisms, including growth arrest in rheumatoid arthritis synovial fibroblasts (RASFs), suppression of pro-inflammatory cytokines or chemokines, anti-angiogenesis as well as protective effects on bone and cartilage destruction will also be discussed. Current literatures strongly imply HDAC inhibitors as innovative anti-rheumatic drug candidates. However, long-term safety is a major concern. Future investigations should focus on identification of molecular anti-rheumatic mechanisms, development of new classes of HDAC inhibitors with better safety and selectivity profiles, combination of HDAC inhibitors with disease modifying anti-rheumatic drugs (DMARDs) and establishment of topical or intraarticular formulations.

Keywords: Epigenetic regulation, histone deacetylase inhibitor, rheumatoid arthritis, growth arrest, pro-inflammatory cytokine, angiogenesis, osteoclastogenesis, nuclear factor kappa-B