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    • 5. 发明申请
    • THERAPEUTIC METHODS FOR VASCULAR INJURY
    • 用于血管损伤的治疗方法
    • WO1998019686A1
    • 1998-05-14
    • PCT/US1997020404
    • 1997-11-07
    • REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN DIEGOCHIEN, ShuSHYY, John, Y.-J.
    • REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN DIEGO
    • A61K31/70
    • C12N9/1205A61K38/00C07K14/82C12N2799/022
    • The present invention comprises methods of treating disorders associated with vascular injury from mechanical stimuli including restenosis, atherosclerosis and reperfusion injury. In one embodiment of the invention gene therapy techniques are applied using genes encoding a variety of proteins that play key roles in transducing an extracellular signal through to the nucleus including src, Ras, MEKK and JNK. These proteins are mutated such that they are rendered signal transduction incompetent, thus abrogating their ability to induce a cellular response. The invention further encompasses viral gene therapy vectors containing genes encoding these signaling incompetent mutants and pharmaceutical compositions. Additional embodiments of the invention encompass alternative means of inhibiting the key signal transduction pathways related to mechanical injury. One alternative includes the use of antisense versions of genes encoding key proteins such as src, Ras, MEKK, JNK and the like. Chemical compounds acting as enzymatic inhibitors or disrupters of protein:protein interactions are also contemplated by the present invention.
    • 本发明包括从机械刺激(包括再狭窄,动脉粥样硬化和再灌注损伤)治疗与血管损伤相关的疾病的方法。 在本发明的一个实施方案中,使用编码多种蛋白质的基因来应用基因治疗技术,所述蛋白质在将细胞外信号转导到包括src,Ras,MEKK和JNK的细胞核过程中发挥关键作用。 这些蛋白质被突变,使得它们变成信号转导不称职,从而消除其诱导细胞反应的能力。 本发明还包括含有编码这些信号传导不足突变体和药物组合物的基因的病毒基因治疗载体。 本发明的另外的实施方案包括抑制与机械损伤相关的关键信号转导途径的替代手段。 一种替代方案包括使用编码关键蛋白质如src,Ras,MEKK,JNK等的基因的反义形式。 作为蛋白质的蛋白质相互作用的酶抑制剂或蛋白质相互作用的化学化合物也在本发明中。