SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Department of Pharmacology, V. M. Road, Vile Parle (W), Mumbai, India.
Department of Pharmaceutical Analysis, Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, V. M. Road, Vile Parle (W), Mumbai, India.
Int Immunopharmacol. 2022 Aug;109:108794. doi: 10.1016/j.intimp.2022.108794. Epub 2022 Apr 30.
Rheumatoid arthritis (RA) is an autoimmune disorder that is slow progressive destruction of the joints and is caused by autoantibodies that target a variety of organs thereby leading to auto-destruction. Patients diagnosed with RA develop deformity of joints and show gradual functional impairment if they do not receive treatment within the desired timeline. The availability of biological treatments and the introduction of treat-to-target regimens have dramatically enhanced the outcome for patients treated with RA conditions. Nevertheless, there is still attention required for RA because patients do not respond adequately to currently available treatment regimens. Over the past few decades, newer therapy methods are evolving to better understand the in-depth literature behind the actual cause of RA. Thus, getting an insight into the importance of RA there is a need for a shift in the existing treatment. This article focuses on a comprehensive review of the therapeutic potential of newer targets such as Janus Kinase-signal transducer and activator of transcription pathway, Granulocyte macrophage-colony stimulating factor, Bruton's Tyrosine Kinase Pathway, Phosphoinositide-3-kinase Pathway, Dendritic cells, Neuropathway, Receptor activator of nuclearfactor-kappa-Β ligand (RANKL) Inhibitors, Mesenchymal Stem Cells and Synovial Anatomy emphasizing on Synovial fibroblasts Myeloid Cells which have been summarized. In addition, novel therapeutic targets such as proteins, small molecular metabolites, and epigenetics are described in this article. Cytokines, chemokines, and other protein targets are among the protein target. Prostaglandins, leukotrienes, platelet-activating factor, cannabinoids, and specific fatty acid amide hydrolase are all examples of small molecular metabolites. DNA, RNA, and Histone Modification are epigenetic targets. Furthermore, the article provides an in-depth understanding of the exact mechanism in underlying pathophysiology in RA and thereby substantiating their evident therapeutic effect with ongoing clinical trials. Nevertheless, these newer targets would help to bring and paradigm shift in the treatment of this ancient autoimmune disorder.
类风湿关节炎(RA)是一种自身免疫性疾病,其特征是关节进行性缓慢破坏,由针对多种器官的自身抗体引起,从而导致自身破坏。如果患者在理想时间内未接受治疗,RA 会导致关节畸形并逐渐出现功能障碍。生物治疗的出现和靶向治疗方案的引入极大地改善了 RA 患者的预后。然而,RA 仍需要引起重视,因为患者对现有治疗方案的反应并不充分。在过去的几十年中,新的治疗方法不断发展,以更好地了解 RA 实际病因的深入文献。因此,深入了解 RA 的重要性,需要对现有治疗方法进行转变。本文重点综述了新的治疗靶点的治疗潜力,如 Janus 激酶-信号转导和转录激活因子途径、粒细胞-巨噬细胞集落刺激因子、布鲁顿酪氨酸激酶途径、磷酸肌醇 3-激酶途径、树突状细胞、神经通路、核因子-κB 配体(RANKL)抑制剂、间充质干细胞和滑膜解剖学,强调了滑膜成纤维细胞和髓样细胞的重要性。此外,本文还描述了新型治疗靶点,如蛋白质、小分子代谢物和表观遗传学。细胞因子、趋化因子和其他蛋白质靶点属于蛋白质靶点。前列腺素、白三烯、血小板激活因子、大麻素和特定的脂肪酸酰胺水解酶都属于小分子代谢物。DNA、RNA 和组蛋白修饰属于表观遗传学靶点。此外,本文深入了解了 RA 潜在病理生理学的确切机制,从而证实了正在进行的临床试验中的明显治疗效果。然而,这些新的治疗靶点将有助于为这种古老的自身免疫性疾病带来治疗模式的转变。