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首页 » 老年性痴呆 » Brain最新研究再掀tau-β淀粉蛋白之争,百健(Biogen)突破性进展被泼冷水!

Brain最新研究再掀tau-β淀粉蛋白之争,百健(Biogen)突破性进展被泼冷水!

来源:生物谷 2015-03-24 15:24

2015年3月24日讯 /生物谷BIOON/ --上周五,百健(Biogen)公布了其实验性阿尔茨海默氏症(AD)药物BIIB037激动人心的早期数据。然而,本周来自梅奥诊所(Mayo Clinic)的一项最新研究,却给百健的突破性进展迎头泼了一盆冷水,该研究可能会重新掀起有关制药行业在研AD药物是否真的找到了正确靶标的长期争论。

本周二发表于神经学期刊《大脑》(Brain)上的最新研究中,来自梅奥诊所的研究人员发现,tau蛋白的异常积累是阿尔茨海默氏症(AD)患者认知衰退和记忆丧失的真正源头。研究人员发现,tau蛋白破坏了整个大脑中细胞用于运输食物和信息的通道。而百健艾迪的药物BIIN037及其他几个处于后期研发阶段的药物,则靶向的是另一种蛋白——β淀粉样蛋白(β-amyloid)。

梅奥诊所神经科学家Melissa Murray在接受电话采访时表示,β淀粉样蛋白与认知功能衰退有关,但如果将它和tau放在一起看,tau才是坏分子。而在过去的25年间,关于阿尔茨海默氏症(AD)的大多数研究都集中于β淀粉样蛋白。

在该项最新研究中,研究人员调查了超过3600例死于不同阶段老年痴呆症的患者的大脑,其中近1400例患者确诊阿尔茨海默氏症(AD)。通过检测疾病进展各个阶段大脑中的β淀粉样蛋白和tau蛋白,研究人员得出结论,tau蛋白水平能够预测患者认知恶化的速度。

Murray指出,当异常tau蛋白在大脑记忆中心——海马(hippocampus)中积累时,认知能力通常开始下降。最终,有毒的tau蛋白会在大脑皮层(cortex)中聚集,而这部分大脑参与了更高层次的思考、规划、行为及注意力。

目前,包括强生(JNJ)、百健(Biogen)、艾伯维(AbbVie)在内的多家制药公司,有一些处于早期阶段的产品靶向tau蛋白。另一家制药公司TauRx Pharmaceuticals目前正在更广泛的临床试验中调查另一种tau靶向药物。

阿尔茨海默氏症(AD)协会科学倡议理事Dean Harley表示,梅奥诊所的研究并没有降低β淀粉样蛋白可能参与阿尔茨海默氏症(AD)疾病进展的思想高度。这些结果可能表明,科学家需要考虑多种方法和多个靶标。这取决于患者所处的疾病阶段,可能需要特定类型的治疗药物。如果处于疾病晚期,可能tau蛋白是及其重要的,但如果我们不希望有任何临床症状出现,那么我们要做的可能是靶向β淀粉样蛋白。

百健(Biogen)的突破性数据:

上周五,百健发布了实验性阿尔茨海默氏症(AD)药物BIIB037一项Ib期临床研究结果,数据显示BIIB037明显逆转了β淀粉样蛋白在大脑中的聚集,并且在降低认知能力下降方面也表现出积极的迹象。消息发布后该公司股价飙升10%。有分析师预计,如果BIIB037在III期临床获得成功并上市,该药将成为百健和合作伙伴日本卫材(Eisai)年销超100亿美元的重磅产品。

不过,这只是处于临床开发的一个β淀粉样蛋白靶向药物。礼来目前也在调查另一种单抗solanezumab用于较早阶段的患者。而罗氏,尽管在去年12月因糟糕数据终止了一种β淀粉样蛋白靶向药物在早期阶段AD患者的研究,但仍正继续推进该药用于轻度痴呆症的AD患者。(生物谷Bioon.com)

参考文献

 

Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum

DOI: http://dx.doi.org/10.1093/brain/awv050

英文原文:New Alzheimer's Research Throws Cold Water on Biogen's Recent Breakthrough

(Bloomberg) -- Just days after Biogen Inc. revealed promising early data from an experimental Alzheimer’s treatment, new research from the Mayo Clinic may revive a long-running debate over whether the drug industry is focusing on the right target in developing therapies to treat the disease.

The study, published Tuesday in the journal Brain, found that the accumulation of dysfunctional tau protein is the real source of cognitive decline and memory loss seen in Alzheimer’s. Tau destabilizes tracks used by cells to transport food and messages throughout the brain, the research found.

Biogen’s drug BIIB037, and several others in advanced development, focus instead on the buildup of different set of protein fragments, called beta amyloid.

“Amyloid has a relationship with cognitive decline, but if you’re looking at both of them together, tau is the bad guy,” Melissa Murray, a neuroscientist at the Mayo Clinic campus in Jacksonville, Florida, said in a telephone interview. The majority of research into the disease has focused on beta amyloid over the past 25 years, she said.

The researchers examined more than 3,600 brains from patients who died at different stages of dementia, with Alzheimer’s confirmed in almost 1,400. Measuring amyloid and tau in the brains at various stages of disease progression allowed them to conclude that it was the level of tau that predicted how quickly a person’s mental faculties had deteriorated.

Cognitive decline typically begins when abnormal tau accumulates in the memory center of the brain –- the hippocampus. Ultimately, toxic tau accumulates in the cortex, the part of the brain involved in higher levels of thinking, planning, behavior and attention, Murray said.

Drug Development Companies including Johnson & Johnson, Biogen and AbbVie Inc. have products in the early stages of development that target tau in the brain. TauRx Pharmaceuticals Ltd., a closely held, Singapore-based drug developer, is testing a tau-targeting compound in broader human trials.

The Mayo Clinic study doesn’t discount the idea that beta amyloid may be involved in Alzheimer’s progression. The findings may indicate that scientists need to consider multiple approaches and targets, said Dean Hartley, director of science initiatives at the Alzheimer’s Association.

“Depending on where you are in the disease, you may need certain types of treatments,” Hartley said. “If you’re later in the disease, maybe tau is extremely important, but if we don’t want any of the clinical symptoms to develop, then maybe we want to target amyloid.”

Promising Data
On Friday, Biogen released early-stage clinical trial data showing that its experimental Alzheimer’s drug clearly reversed the build-up of beta amyloid in the brain and also showed signs of reducing cognitive decline. The company’s shares shot up 10 percent on the news. Analysts said the therapy, if successful in later-stage trials and approved, could become a more than $10 billion drug for Biogen and partner Eisai Co.

That’s just one amyloid-targeting therapy in trials. Eli Lilly & Co. is currently retesting its drug solanezumab in earlier-stage patients. Roche Holding AG is continuing to sponsor a trial of its amyloid-targeting drug in Alzheimer’s patients with mild dementia, though in December it abandoned a study of people with early stages of the disease because of poor results.

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