| 翻訳と辞書 |
Mydicar
Mydicar is a genetically targeted enzyme replacement therapy being studied for use in patients with severe heart failure. It is designed to increase the level of SERCA2a, a sarcoplasmic endoplasmic reticulum calcium (Ca2+) ATPase found in the membrane of the sarcoplasmic reticulum (SR). The SERCA2a gene is delivered to the heart via an adeno-associated viral vector.〔Jaski BE, Jessup ML, Mancini DM, Cappola TP, Pauly DF, Greenberg B, et al. (2010). "Calcium Upregulation by Percutaneous administration of gene therapy In cardiac Disease (CUPID Trial), a first-in-human phase 1/2 clinical trial". ''Journal of Cardiac Failure''. 15(3):171-181.〕 Using the α-myosin heavy chain gene promoter in the cardiac muscle cells, also called cardiomyocytes, Mydicar is able to direct the gene expression only to the heart muscle.〔Baker DL, Hashimoto K, Grupp IL, Ji Y, Reed T, Loukianov E, et al. (1998). "Targeted overexpression of the sarcoplasmic reticulum Ca2+-ATPase increases cardiac contractility in transgenic mouse hearts". ''Circulation Research''. 83:1205–1214.〕 Mydicar is being tested in a phase 2 study, in which has been compared to a placebo in 39 advanced heart failure patients.〔Greenberg B, Jessup ML, Zsebo KM, Yaroshinsky A and Hajjar RJ. (2010). "CUPID 1: MYDICAR in patients with advanced heart failure continue to demonstrate improvement in clinical outcomes compared to optimal therapy 9 months post-dose". ''Journal of Cardiac Failure''. 16(11): 911.〕 Thus far, patients treated with Mydicar have shown a 52% reduction in the risk of worsening heart failure compared to patients treated with the placebo.〔
==The role of SERCA2a in the heart==
Normal function of the heart involves proper coordination between the contraction and relaxation of cardiomyocytes. Proper contraction and relaxation depends on the coordinated rise and fall of Ca2+ in the cytosol of the cardiomyocytes.〔del Monte F, Harding SE, Schmidt U, Matsui T, Bin Kang Z, Dec GW, et al. (1999). "Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a". ''Circulation''. 100:2308–2311.〕 The SERCA2a transporter is found in the membrane of the SR and plays an important role in this cycle by removing cytosolic Ca2+ from the cardiomyocyte and pumping it back into the SR during relaxation of the heart (diastole). SERCA2a restores SR Ca2+ for the next contraction of cardiomyocytes.〔Lipskaia L, Chemaly ER, Hadri L, Lompre A, and Hajjar RJ. (2010). "Sarcoplasmic reticulum Ca2+ ATPase as a therapeutic target for heart failure" ''Expert Opinion on Biology Therapy''. 10(1):29–41.〕 SERCA2a activity declines in patients experiencing late-stage heart failure.〔 This leads to an above normal amount of cytosolic Ca2+ in the cardiomyocytes during diastole. It also results in less Ca2+ remaining in the SR for the next contraction of the heart. The altered cycling of Ca2+ in cardiomyocytes ultimately leads to improper functioning of the heart, indicating a potentially beneficial effect of gene therapy using Mydicar.〔
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
■ウィキペディアで「Mydicar」の詳細全文を読む
スポンサード リンク
| 翻訳と辞書 : 翻訳のためのインターネットリソース |
Copyright(C) kotoba.ne.jp 1997-2016. All Rights Reserved.
|
|