Fighting rheumatoid arthritis: Kv1.3 as a therapeutic target

Abstract

Abstract Rheumatoid arthritis (RA) is a serious autoimmune disease that has severe impacts on both the wellbeing of patients and the economy of the health system. Similar to many autoimmune diseases, RA concurs with a long evolution, which eventually results in highly debilitating symptoms. Therapeutic treatments last for long periods during RA. However, their efficiency and side effects result in suboptimal conditions. Therefore, the need for specific, safer and nontoxic alternatives for the treatment of RA is essential. Kv1.3 is a voltage-gated potassium channel that has a crucial role in immune system response. The proliferation and activation of leukocytes are linked to differential expressions of this channel. The evidence is particularly relevant in the aggressive T effector memory (TEM) cells, which are the main actors in the development of autoimmune diseases. Blockage of Kv1.3 inhibits the reactivity of these cells. Furthermore, pharmacological inhibition of Kv1.3 ameliorates symptoms in animal models of autoimmune diseases, such as experimental autoimmune encephalomyelitis or induced psoriasis with no side effects. Kv1.3 is sensitive to several animal toxins and plant compounds, and several research groups have searched for new Kv1.3 blockers by improving these natural molecules. The research is mainly focused on enhancing the selectivity of the blockers, thereby reducing the potential for side effects on other related channel subunits. Higher selectivity means that treatments will potentially be less harmful. This leads to a lower discontinuation rate of the therapy than the current first-line treatment for RA. The molecular backgrounds of many autoimmune diseases implicate leukocyte Kv1.3 and suggests that a new medication for RA is feasible. Therapies could also be later repurposed to treat other immune system disorders.