Molecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina Universitat de Barcelona (IBUB), Barcelona, Spain.
Molecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina Universitat de Barcelona (IBUB), Barcelona, Spain.
Biochem Pharmacol. 2019 Jul;165:214-220. doi: 10.1016/j.bcp.2019.03.016. Epub 2019 Mar 14.
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 (T) 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.
类风湿性关节炎（RA）是一种严重的自身免疫性疾病，对患者的健康和医疗系统的经济都有严重影响。与许多自身免疫性疾病类似，RA 的病程很长，最终会导致高度衰弱的症状。RA 的治疗需要长期进行。然而，它们的疗效和副作用导致治疗效果并不理想。因此，需要针对 RA 治疗的特定、更安全、无毒的替代方法。Kv1.3 是一种电压门控钾通道，在免疫系统反应中起着关键作用。白细胞的增殖和激活与该通道的差异表达有关。这一证据在侵袭性 T 效应记忆（T）细胞中尤为重要，这些细胞是自身免疫性疾病发展的主要参与者。阻断 Kv1.3 可抑制这些细胞的反应性。此外，Kv1.3 的药理学抑制可改善自身免疫性疾病的动物模型中的症状，如实验性自身免疫性脑脊髓炎或诱导性银屑病，且无副作用。Kv1.3 对几种动物毒素和植物化合物敏感，几个研究小组通过改进这些天然分子来寻找新的 Kv1.3 阻断剂。研究主要集中在提高阻断剂的选择性上，从而降低对其他相关通道亚基产生副作用的可能性。更高的选择性意味着治疗的潜在危害更小。这导致治疗的停药率比目前 RA 的一线治疗要低。许多自身免疫性疾病的分子背景都涉及白细胞 Kv1.3，并表明针对 RA 的新药物治疗是可行的。这些疗法以后也可能被重新用于治疗其他免疫系统疾病。
