Suneetha A, Raja Rajeswari K
Department of Pharmaceutical Analysis, Hindu College of Pharmacy, Amaravathi Road, Guntur 522 002, Andhra Pradesh, India.
College of Pharmaceutical Sciences, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur 522510, Andhra Pradesh, India.
J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 15;1019:15-20. doi: 10.1016/j.jchromb.2016.02.010. Epub 2016 Feb 8.
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via oxidative stress pathway. The rapid screening methods are also need to be developed to estimate DMF in biological samples to perform and proceed for further investigations.
多发性硬化症（MS）是一种影响中枢神经系统白质和灰质的慢性炎症性疾病。炎症和氧化应激也被认为会促进多发性硬化症中的组织损伤。最近的数据表明抗氧化途径在慢性MS的组织保护中起重要作用，特别是涉及转录因子核因子（红系衍生2）相关因子2（Nrf2）。因此，增强细胞对自由基抗性的新型疗法可能对MS治疗有用。氧化应激和抗氧化途径是MS病理生理学中的重要因素，并且构成了未来用富马酸二甲酯治疗MS的有希望的靶点。正在通过使用口服治疗剂BG-12的III期试验探索DMF在多发性硬化症中的临床效用。目前正在进行广泛的研究以找出DMF的确切机制，迄今为止尚不清楚。基于非人类中肾毒性的强烈信号以及富马酸盐细胞内积累导致肾细胞癌的理论风险，需要对大量患者进行上市后研究以充分评估富马酸二甲酯的长期安全性。当前的治疗目标是缩短复发的持续时间和严重程度，延长复发之间的时间，并延缓残疾进展。在这方面，富马酸二甲酯为口服芬戈莫德（GILENYA）或特立氟胺（AUBAGIO）提供了有希望的替代方案，由于严重的安全问题，这两种药物目前在美国根据FDA强制要求的风险评估和缓解策略（REMS）计划销售。对于诊断为多发性硬化症的患者，需要更多使用这三种药物的临床经验来区分长期治疗的耐受性。本报告提供了富马酸二甲酯治疗神经疾病多发性硬化症及其通过氧化应激途径涉及的机制的详细信息。还需要开发快速筛选方法来估计生物样品中的DMF，以便进行进一步的研究。
