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治疗代谢紊乱的单克隆抗体:主要进展和未来展望。

Therapeutic Monoclonal Antibodies for Metabolic Disorders: Major Advancements and Future Perspectives.

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Export Promotions Industrial Park (EPIP), Vaishali, Hajipur, 844102, Bihar, India.

出版信息

Curr Atheroscler Rep. 2024 Oct;26(10):549-571. doi: 10.1007/s11883-024-01228-0. Epub 2024 Jul 15.

Abstract

PURPOSE OF REVIEW

Globally, the prevalence of metabolic disorders is rising. Elevated low-density lipoprotein (LDL) cholesterol is a hallmark of familial hypercholesterolemia, one of the most prevalent hereditary metabolic disorders and another one is Diabetes mellitus (DM) that is more common globally, characterised by hyperglycemia with low insulin-directed glucose by target cells. It is still known that low-density lipoprotein cholesterol (LDL-C) increases the risk of cardiovascular disease (CVD). LDL-C levels are thought to be the main therapeutic objectives.

RECENT FINDINGS

The primary therapy for individuals with elevated cholesterol levels is the use of statins and other lipid lowering drugs like ezetimibe for hypercholesterolemia. Even after taking statin medication to the maximum extent possible, some individuals still have a sizable residual cardiovascular risk. To overcome this proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors-monoclonal antibodies (mAbs) are a novel class of systemic macromolecules that have enhanced LDL-C-lowering efficacy. Along with this other inhibitor are used like Angiopoeitin like 3 inhibitors. Research on both humans and animals has shown that anti-CD3 antibodies can correct autoimmune disorders like diabetes mellitus. Individuals diagnosed with familial hypercholesterolemia (FH) may need additional treatment options beyond statins, especially when facing challenges such as statin tolerance or the inability of even the highest statin doses to reach the desired target cholesterol level. Here is the summary of PCSK9, ANGPTL-3 and CD3 inhibitors and their detailed information. In this review we discuss the details of PCSK9, ANGPTL-3 and CD3 inhibitors and the current therapeutic interventions of using the monoclonal antibodies in case of the metabolic disorder. We further present the present studies and the future prospective of the same.

摘要

综述目的

在全球范围内,代谢紊乱的患病率正在上升。升高的低密度脂蛋白(LDL)胆固醇是家族性高胆固醇血症的标志之一,家族性高胆固醇血症是最常见的遗传性代谢紊乱之一,另一种更为普遍的代谢紊乱是糖尿病(DM),其特征是高血糖伴靶细胞胰岛素指导的葡萄糖摄取减少。人们仍然知道,低密度脂蛋白胆固醇(LDL-C)会增加心血管疾病(CVD)的风险。LDL-C 水平被认为是主要的治疗目标。

最新发现

对于胆固醇水平升高的个体,主要的治疗方法是使用他汀类药物和其他降脂药物,如依折麦布治疗高胆固醇血症。即使最大限度地服用他汀类药物,一些人仍然存在相当大的残余心血管风险。为了克服这一问题,前蛋白转化酶枯草溶菌素 9(PCSK9)抑制剂-单克隆抗体(mAbs)是一类新型的系统大分子,具有增强的 LDL-C 降低作用。除此之外,还使用了血管生成素样 3 抑制剂等其他抑制剂。人类和动物的研究表明,抗 CD3 抗体可以纠正像糖尿病这样的自身免疫性疾病。家族性高胆固醇血症(FH)患者可能需要除他汀类药物以外的其他治疗选择,特别是在面临他汀类药物耐受或即使最高剂量的他汀类药物也无法达到所需的目标胆固醇水平等挑战时。以下是 PCSK9、ANGPTL-3 和 CD3 抑制剂的概述及其详细信息。在本次综述中,我们讨论了 PCSK9、ANGPTL-3 和 CD3 抑制剂的细节,以及在代谢紊乱的情况下使用单克隆抗体的当前治疗干预措施。我们进一步介绍了目前的研究和未来的前景。

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