UK firm Karus Therapeutics has included selective HDAC-6 inhibitors in its HDAC drug discovery programme.
A series of these small molecules recently developed by Karus have displayed important anti-inflammatory activity, mainly in preclinical models of rheumatoid arthritis, as well as immunosuppressive qualities.
The HDAC inhibitors' development has predominantly targeted cancer treatment, and preclinical in vitro and in vivo models have shown that HDAC-6 inhibition leads to increased expression of the FOXP3 transcription factor.
The FOXP3a protein plays a key role in the development and immunosuppressive function of regulatory T-cells in relation to chronic diseases including rheumatoid arthritis, psoriasis, multiple sclerosis, lupus and organ transplant rejection.
The selective HDAC-6 inhibitors are also expected to work as neuroprotectants in Alzheimer's disease and related neurodegenerative diseases.