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为了攻克阿尔茨海默症,Alzheon这次拉来了朊病毒研究诺奖得主Stanley Prusiner

2017-01-16 动脉网/周倩昀 动脉网/周倩昀

一些生物技术创业公司,如今正在重新研发一个曾经失败的候选药物,旨在以精确的方法治疗阿尔茨海默病。这个尝试中有一个伟大的人物参与其中,他就是诺贝尔奖获得者——博士Stanley Prusiner,作为研究(阿尔茨海默病)疾病的先驱。 诺奖得主Stanley Prusiner,旧金山加州大学的生物学家 Alzheon创始人兼首席执行官Martin Tolar博士说,Stanley Pr

一些生物技术创业公司,如今正在重新研发一个曾经失败的候选药物,旨在以精确的方法治疗阿尔茨海默病。这个尝试中有一个伟大的人物参与其中,他就是诺贝尔奖获得者——博士Stanley Prusiner,作为研究(阿尔茨海默病)疾病的先驱。

诺奖得主Stanley Prusiner,旧金山加州大学的生物学家

Alzheon创始人兼首席执行官Martin Tolar博士说,Stanley Prusiner作为旧金山加州大学的生物学家,将加入Alzheon公司担任科学咨询委员会主席这一职位。

阿尔茨海默症背后真凶

Alzheon公司是一家初露初露端倪的小型生物技术企业,正投身于阿尔茨海默氏症(AD)新药开发大军。它另辟蹊径开发的新药ALZ-801是一种针对β-淀粉样蛋白的拮抗剂老药tramiprosate(homotaurine,高牛磺酸)改良而成的优化前体药物,而tramiprosate在十年前曾被搁置开发的。Alzheon公司认为,基于当前阿尔茨海默氏症研究领域的最新进展,ALK-801具有涅盘重生的潜力,为部分阿尔茨海默病患者带来希望。

实验中越来越多的证据表明,我们可以通过淀粉样蛋白β斑块和tau缠结的蛋白质团块的关系来定义阿尔茨海默病,这项疾病与朊病毒共享特征,Prusiner在20世纪80年代发现的这种奇怪的“感染性蛋白质”可能就是阿尔茨海默病背后的真凶。 朊病毒在它们自我繁殖和不断积累时还会引发各种神经性疾病,例如克雅氏病(Creutzfeldt-Jakob disease)。

特别地,如今研究已经表明蛋白质tau和淀粉样蛋白-β自身组装成团块,正如蛋白质在朊病毒疾病中的作用一样,这些团块从一个异常分子开始,将会不断在人体的整个大脑中传播。

Tolar说,“Alzheon公司研发的先导化合物会阻止淀粉样蛋白的聚集和增殖。”这种先导化合物以粘性斑块的形式存在于大脑中,如今被我们认为是阿尔茨海默病的独特特征。另外,牵涉阿尔茨海默病的另一种蛋白质,似乎也是通过这种朊病毒的传播过程在人体的大脑中形成了纤维样缠结。

Prusiner由于他在研究朊病毒方面的杰出贡献获得了1997年诺贝尔医学和生理学奖。

Alzheon公司显然希望Stanley Prusiner的专业知识能够帮助他们,同时这种合作关系也是双向的。 Alzheon公司如今在对5000组分子进行研究,这些实验或许对Prusiner正在UCSF所做的朊病毒方面的研究也会带来进展。Tolar在20世纪90年代第一次见到Prusiner,那个时候他作为研究生被邀请去在英国皇家医学研究中心辛辛那提大学,和众多著名的生物学家对众多生物话题一起进行研讨。

精确治疗阿尔茨海默病疗法

Alzheon研发的先导化合物,称为ALZ-801,是近10年内由如今已经破产的公司Neurochem在3期临床试验中失败的一种化合物。

但Alzheon公司重新描述其方法为“精确治疗阿尔茨海默病疗法”,同时认为该化合物在对于治疗携带两个拷贝的ApoE4基因变体的阿尔茨海默病患者中最为有效。它计划今年仅在携带两个拷贝的ApoE4基因变体患者中进行临床试验,这项实验可能会给ALZ-801(也称为tramiprosate)的效用呈现一个更好的平台。

该化合物ALZ-801可以保持可溶性淀粉样蛋白,以免他们聚集成斑块来破坏人体的神经突触。

Prusiner在向STAT网站报告的一个声明中说,“我们应该注意到困扰阿尔茨海默氏研究的这项“复杂的化合物”的僵局,同时我们面前所面临的前进的道路是“在一个可能有希望的新颖的想法中汇集所有的有研发新型药物经验的科学家。所以,这也是我为什么选择与Alzheon合作,我期待为ALZ-801的发展贡献我自己的经验和见解。”

早期的誓言迹象表明,在临床试验中,ApoE4患者的ALZ-801的记忆和认知效果已经非常强了,因此我们不需要数以千计的患者同时进行试验。虽然这些试验的细节没有公开,因为公司需要与食品和药物管理局进行协商,Tolar认为这些实验完全可以只需要几百个病人的参与。

 

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    2017-02-01 Lidu20002000

    新药带来新希望

    0

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    2017-01-18 wumeihua90
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