We are interested in potassium channels as therapeutic targets. We identified the pivotal role of potassium channels (Kv1.3 and KCa3.1) in the immune response. We have developed specific blockers of these channels. Selective Kv1.3 blockers treat disease in rodent models of multiple sclerosis, rheumatoid arthritis, type-1 diabetes mellitus, psoriasis, autoimmune glomerulonephritis, and contact dermatitis, and they have been shown to be safe in rats and monkeys. ShK-186, a peptide inhibitor of Kv1.3, is scheduled to begin human trials in 2011. Selective KCa3.1 blockers have been shown to prevent vascular stenosis following angioplasty in rats and atherosclerosis in mice. We also developed a transgenic model for cerebellar ataxia based on targeting the KCa2.x potassium channel in deep cerebellar neurons. The results from this study suggested the possibility of using KCa2.x channel-openers as therapy for cerebellar ataxia. Based on this work a clinical trial of riluzole in cerebellar ataxia was performed in Italy and the drug was found to be effective in reducing the symptoms of the disease.
Esophagus: Molecules to Disease Management (Board Review)