Immune diseases

The complexity of the human immune system is reflected in the multiple cellular regulation mechanisms it uses.  The activity and function of immune cells are regulated by various ion channels, making them attractive targets for inflammatory and auto-immune disease drug development. Academic and industry groups have developed antibodies, peptide toxins, and small molecule modulators for many of these immune cell ion channels. A  derivative of a sea anemone toxin (ShK-186, Dalazatide) successfully reduced plaque psoriasis symptoms in a clinical trial, validating this drug discovery approach to treat inflammatory auto-immune disease. There is great interest in using a similar approach to regulate the activity of microglia in the brain to treat neuro-inflammatory and neurodegenerative diseases.

A number of ion channels have been implicated in rheumatoid arthritis, a chronic autoimmune disease which manifests as inflammation within the synovial joints. It has been proposed that the ligand-gated ion channel, ASIC1a, plays a crucial role in the pathogenesis of rheumatoid arthritis. promoting inflammation, synovial hyperplasia, and destruction of bone which lead to the progression of the disease. The voltage-gated ion channels, K_V1.3 and K_Ca1.1 have also been proposed to play a role in rheumatoid arthritis by regulating fibroblast-like synoviocytes and T memory cells and a combined therapy of K_V1.3 and K_Ca1.1 blockers may prove to be a more effective treatment for the disease than one treatment type alone to slow progression of the disease.