2022年邵逸夫奖获奖名单公布!两名美国科学家因发现了囊性纤维化机制获生命科学与医学奖

2022-05-27 MedSci原创 MedSci原创

邵逸夫奖为国际性奖项,以表彰在学术及科学研究或应用上获得突破性成果,并对人类生活产生深远影响的科学家。

邵逸夫奖基金会24日召开线上新闻发布会,公布2022年邵逸夫奖获奖名单,共有6位科学家获奖。

邵逸夫奖创立于2002年11月,由邵逸夫奖基金会管理及执行。该奖设有三个奖项,分别为天文学、生命科学与医学、数学科学,每项奖金120万美元。

生命科学与医学奖平均颁予美国福泰制药公司圣地亚哥研究部高级副总裁保罗·内古列斯库和美国艾奥瓦大学内科学系教授迈克尔·威尔士,获奖原因是他们发现了囊性纤维化是分子、生物化学和功能上出现缺陷所引致,并鉴别和研发新药物去修复这些缺陷,从而能够治疗大多数患者。

保罗·内古列斯库(Paul A. Negulescu),美国福泰制药公司(Vertex)圣地亚哥研究部高级副总裁暨研究部主管。

内古列斯库分别于1986年和1990年获得美国加州大学伯克利分校生理学学士学位及博士学位。他先后在美国加州大学伯克利分校和尔湾分校从事博士后研究工作。他于1996年加入美国圣地亚哥极光生物科技公司成为第一批员工,并与公司一起成长,之后更成为发现生物学部高级副总裁(1999–2001)。2001年福泰制药公司收购极光生物科技公司,他被委任为研究部高级副总裁(2001–)。

迈克尔·威尔士(Michael J Welsh),美国爱荷华大学内科学系教授(肺科、重症监护和职业病医学),神经外科、神经科、分子生理及生物物理教授;霍华德休斯医学研究所研究员,Pappajohn生物医学研究所所长。

2022年度邵逸夫生命科学与医学奖平均颁予保罗·内古列斯库(Paul A. Negulescu)和迈克尔·威尔士(Michael J Welsh),以表彰他们发现囊肿性纤维化是分子、生物化学和功能上出现缺陷所引致,以及鉴别和研发新药物去修复这些缺陷,因而能够治疗大多数患者。这些发现和药物不但减轻人类的痛苦,并拯救了无数生命。

囊性纤维化(Cystic Fibrosis,CF)是一种很常见的严重单基因遗传疾病,全球有超过80,000人受影响。发生突变而致病的单个基因称为囊性纤维化跨膜调节器(Cystic Fibrosis Transmembrane Regulator),简称CFTR。CFTR蛋白的功能是确保氯离子的正常流动。氯离子是盐的一种成分,存在于人体分泌出来的体液,如汗液、唾液和黏液之中。这些液体能保持细胞润滑,对器官功能的正常运作十分重要。在囊性纤维化患者中,这些分泌物会变得浓缩而黏稠,不能充当润滑剂,尤其是肺部的分泌物,更会堵塞通道,引起致命的病变。很多CFTR中不同的突变都会导致患病,但其中一种称为F508del的突变尤其重要,因为大约90%的CF患者都发现带有这种突变。

来自爱荷华大学的迈克尔·威尔士教授于1990至1991年间发现CFTR蛋白可形成一条氯离子通道,并揭示CFTR蛋白的活性是如何被调节的。他通过提供正常的CFTR基因去纠正培养中的病人细胞的囊性纤维化缺陷,从而证明纠正有缺陷的基因是一种可行的治疗策略。在这个非同寻常的研究(1992–1993)中,威尔士证明了不同的囊性纤维化致病突变是如何影响CFTR蛋白的——有些是抑制CFTR蛋白的制造,有些是干扰CFTR蛋白输送到细胞膜,有些是阻止CFTR蛋白的氯离子运输通道的开放或令该通道失去运输功能。威尔士根据这些机制对不同的人类囊性纤维化突变进行分类,并制定出一个方案来纠正每种类型的潜在缺陷。重要的是,威尔士表明具有常见的F508del突变的CFTR蛋白有多种缺陷,该蛋白不能到达细胞膜,并且在氯离子运输方面也出现问题。非常关键的是,威尔士研发出一个实验条件,使CFTR-F508del蛋白能够进入细胞膜,他还证明当该蛋白确实到达细胞膜时,就能发挥其作用。这个突破性的发现意味着如果可以研发一种治疗策略使CFTR-F508del进入细胞膜,将有利于对抗这种疾病。

来自福泰制药公司的保罗·内古列斯库实现了从机制至治疗的飞跃。他和福泰团队利用一种极具冒险的方法来筛选出可以“修复”缺陷蛋白的化合物,因而发现了能治疗囊性纤维化的小分子。此外,由于有许多不同的突变会引发囊肿性纤维化,他们仍不确定是否可以研发出一种能够治疗大部分囊性纤维化患者的药物。内古列斯库首先发现了一种可刺激CFTR通道功能的CFTR“增强剂”。这种被称为Kalydeco的药物获得了突破性的肯定。然而,Kalydeco只对少数存在某些罕见CFTR突变的囊性纤维化患者有用,而对绝大多数具有CFTR-F508del突变的囊肿性纤维化患者没有效用。在一项更加大胆的研究中,内古列斯库筛选出能够纠正有贩运缺陷的CFTR-F508del蛋白的分子。值得注意的是,他发现了这种名为“蛋白质矫正剂”(protein-corrector)的分子。他将新的分子与Kalydeco结合在一起,命名为Orkambi。他又对Orkambi进行了两次改进,将两种“蛋白质矫正剂”与一种“增强剂”相结合,制造出三联疗法(Trikafta),并于2019年获得批准临床应用。三联疗法能够帮助患有CFTR-F508del突变以及177种罕见CFTR突变的病人。目前,有50%的囊性纤维化患者服用福泰囊肿性纤维化药物。

威尔士和内古列斯库的综合贡献代表了从基础研发到应用到拯救生命的完整生物医药链。他们特别值得授予邵逸夫生命科学与医学奖。

另外,2022年度邵逸夫天文学奖平均颁予两位学者,分别为瑞典隆德大学天文学及理论物理系隆德天文台荣休教授伦纳特·林德格伦和爱尔兰都柏林大学学院物理学院客座教授迈克尔·佩里曼,以表彰他们一生对天体测量学的贡献。

数学科学奖平均颁予美国普林斯顿大学数学教授诺加·阿隆和英国牛津大学默顿数理逻辑讲座教授埃胡德·赫鲁索夫斯基,以表彰他们对离散数学和模型论的非凡贡献,尤其是与代数几何、拓扑和计算机科学的相互影响。

邵逸夫奖理事会主席杨纲凯致辞表示,邵逸夫奖为国际性奖项,以表彰在学术及科学研究或应用上获得突破性成果,并对人类生活产生深远影响的科学家。

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    2022-07-15 wolongzxh
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    2022-12-07 swallow
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    2023-05-12 若水135
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    2022-05-27 ms5983397053539191

    给了🇺🇸人

    0

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