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CTLA4-Ig(阿巴西普):一种有前途的在研药物,有望用于 1 型糖尿病。

CTLA4-Ig (abatacept): a promising investigational drug for use in type 1 diabetes.

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar.

Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Expert Opin Investig Drugs. 2020 Mar;29(3):221-236. doi: 10.1080/13543784.2020.1727885. Epub 2020 Mar 12.

Abstract

: Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells in the pancreas; it leads to the under or nonproduction of insulin. T1D is associated with numerous life-threatening micro- and macro-vascular complications and early deaths, hence the development of preventative strategies is a priority for research.: The authors outline the drawbacks of available treatments for T1D and assess the three key strategies for prevention, including immunomodulatory therapies which hold the most potential. This article examines CTLA4-Ig and its efficacy and safety profiles. Finally, the pharmacokinetic parameters and pharmacodynamic markers of abatacept are shown and in clinical trials, guiding dosage regimen recommendations for future investigational studies.: Immunomodulation is one of the promising strategies for decelerating the progression of beta-cell destruction after the onset of T1D. It holds the advantage of specific immune modulation without systemic general immunosuppression. Preclinical and clinical studies have yielded promising data on the use of CTLA4-Ig in T1D. Variations in response to CTLA4-Ig might be partially explained by the existence of multiple T1D subtypes with varying baseline innate inflammatory/regulatory bias and the rate of C-peptide decline.

摘要

1 型糖尿病(T1D)是一种自身免疫性疾病,由胰腺中产生胰岛素的β细胞破坏引起;它导致胰岛素的产生不足或不产生。T1D 与许多危及生命的微血管和大血管并发症和早期死亡有关,因此制定预防策略是研究的优先事项。

作者概述了可用的 T1D 治疗方法的缺点,并评估了三种预防的关键策略,包括具有最大潜力的免疫调节疗法。本文研究了 CTLA4-Ig 及其疗效和安全性特征。最后,显示了阿巴西普的药代动力学参数和药效学标志物,并在临床试验中,为未来的研究提供了剂量方案建议。

免疫调节是减缓 T1D 发病后β细胞破坏进展的有前途的策略之一。它具有特异性免疫调节而无全身普遍免疫抑制的优势。CTLA4-Ig 在 T1D 中的应用的临床前和临床研究已经产生了有希望的数据。对 CTLA4-Ig 的反应的差异可能部分归因于存在多种 T1D 亚型,这些亚型具有不同的基线固有炎症/调节偏向和 C 肽下降率。

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