在老化的生物学:科学家解决全球性的诊断如何?

Collaborations among pharma, biotech and academic institutes are not uncommon, but typically they’re focused on a certain disease group or therapeutic area, like immunology or oncology.

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An element that makes the AbbVie-Calico partnership unique is an open runway for scientists: Explore, try new experiments, fail, learn, then try again – maybe in a completely different way. Scientists in the partnership are driven by the mission to help understand what makes us age and how to harness these lessons to improve the quality of human health and tackle a plethora of diseases: from cancer and Parkinson’s Disease to genetic ailments and rare conditions.

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The approach has paid off. Established in 2014 and recently extended through 2030, this collaboration has created more than 20 early-stage drug development programs across disease areas including immuno-oncology and neurodegeneration, with three of these programs now in clinical trials. In 2022, the team continues its pursuit of both existing and newly discovered therapeutic targets.

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“Maintaining health as we age is an urgent new frontier for our industry, and 7 years ago we launched a collaboration focused on discovery research to tackle just that,” says Tom Hudson, M.D., AbbVie’s senior vice president, R&D, and chief scientific officer. “What we’ve uncovered is a path to first-in-class medicines to help people living with devastating and potentially life-threatening diseases.”

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合作在制药,生物技术和学术机构并不少见,但通常他们专注于某种疾病组或治疗领域,如免疫学或肿瘤。

一个元素使AbbVie-Calico伙伴关系独特的科学家是一个开放跑道:探索,尝试新的实验,失败,学习,然后再试一次,也许在一个完全不同的方式。伙伴关系是由任务的科学家来帮助理解是什么让我们的年龄和如何利用这些经验教训,以提高人类健康和质量解决大量的疾病:癌症和帕金森病遗传疾病和罕见的条件。

的方法已经得到了回报。成立于2014年,最近延长到2030年,这种合作创造了超过20个早期药物开发项目领域包括immuno-oncology和神经退化疾病,现在三个项目在临床试验中。狗万正网地址2022年,球队继续追求现有的和新发现的治疗靶点。

“维护健康,我们为我们的行业,年龄是一个紧急的新边疆和7年前我们推出了一个专注于研发合作解决,”汤姆·哈德逊说,医学博士AbbVie高级副总裁、研发和首席科学官。“我们发现是通往first-in-class药物帮助人们毁灭性的和潜在的威胁生命的疾病。”

The unique design of this partnership leverages complementary strengths. Calico, which was founded by Alphabet together with CEO Art Levinson, Ph.D., focuses on discovery-stage research and development made possible by advanced technology and computing capabilities.

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“By following the science we create opportunities for new discoveries that allow us to advance the study of human aging as well as identify new therapeutic targets,” says Aarif Khakoo, M.D., Calico head of development and chief medical officer. “Combining this with support from AbbVie, and access to their expertise in many facets of innovative drug development, is essential in achieving our ambitious goal to develop therapies that enable people to lead longer and healthier lives.”

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AbbVie’s discovery and development expertise, coupled with Calico’s research and technological prowess, drives preclinical and clinical programs, with flexibility for scientists to explore as a hallmark of the collaboration, according to Gerry Fox, Ph.D., vice president, discovery & early development, and AbbVie partnership lead.

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“Our disease-agnostic approach, driven by our study of aging biology, has led the joint team to mechanisms we believe are important across a range of diseases including cancer, neurologic disorders and tissue homeostasis disorders like heart and renal disease and diabetes,” Fox says.

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For instance, a deeper look at protein synthesis in brain cells under stress, specifically the accumulation of misfolded protein aggregates found in some neurodegenerative disorders, led the team to advance an approach to counteract this stress and help eliminate these misfolded proteins. Today, a potential treatment using this science is now in clinical trials for people with amyotrophic lateral sclerosis (ALS).

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“We didn’t start out with ALS in mind, but this is where the biology led us,” Fox says. “Many of the targets we’re pursuing can seem very difficult or even ‘undruggable,’ but that’s when the scientists step up with disruptive thinking and technologies.”

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这种伙伴关系的独特设计利用互补优势。棉布,是由字母与首席执行官Art Levinson博士专注于发现阶段的研究和开发成为可能,先进技术和计算能力。狗万正网地址

“遵循科学我们创建新发现的机会,让我们提前研究人类衰老以及确定新的治疗目标,“说Aarif Khakoo,医学博士、印花开发主管和首席医疗官。狗万正网地址“结合AbbVie的支持,和访问他们的经验在许多方面的创新药物开发,实现我们的雄心勃勃的目标开发治疗是至关重要的,使人们更长和更健康的生活。”狗万正网地址

AbbVie的发现和开发经验,加上印花的研究和狗万正网地址技术实力,推动临床前和临床项目,与灵活性科学家探索作为合作的一个标志,格里·福克斯博士,副总裁,领导发现和早期发展和AbbVie伙伴关系。

“我们disease-agnostic方法,推动我们的研究衰老的生物学,导致联合团队机制我们认为是重要的一系列疾病,包括癌症、神经系统疾病和组织内稳态的疾病如心脏和肾脏疾病和糖尿病,”狐狸说。

例如,一个更深层次的看压力下的大脑细胞的蛋白质合成,特别是错误折叠蛋白质的积累总量中发现一些神经退行性疾病,带领团队进步的方法来抵消这个压力和帮助消除这些错误折叠的蛋白质。今天,一个潜在的治疗在临床试验中使用这种科学是现在患有肌萎缩性脊髓侧索硬化症(ALS)。

“我们没有开始记住肌萎缩性侧索硬化症,但这是生物学带领我们,”狐狸说。“许多的目标我们追求似乎非常困难甚至undruggable,但当科学家加强与颠覆性思维和技术。”

One such scientist is Cynthia Kenyon, Ph.D., a leader in molecular biology and Calico’s vice president of aging research. When many thought aging “just happened,” Kenyon hypothesized scientists could control lifespan by changing genes – after all, she reasoned, that’s what evolution did. In the early 1990s, working in her lab at University of California, San Francisco (UCSF), she and her team were able to demonstrate this theory. They doubled the lifespan of a small roundworm called C. elegans after partially inhibiting a gene that allows cells to respond to hormones that control growth and resiliency.

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“When I joined Calico in 2014 I thought I would direct research on aging in my lab, and help educate the community about the logic and mechanistic regulation of aging,” Kenyon says. “But when I got here I realized that I could actually make medicines.”

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Fast forward to today and AbbVie-Calico teams are dedicated to the different biological processes that impact aging, from inflammation to hormone levels to stress response. The research is purposeful, Kenyon says.

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“Because so many diseases are linked to aging, interventions that increase healthspan and lifespan in animals often mitigate these diseases,” she says. “As long as there’s an age-related disease associated with the pathway, we can get it into the pipeline and aim to benefit both specific patient groups and then maybe, ultimately improve quality of life for everyone.”

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就是这样一个科学家辛西娅·凯尼恩博士,一个领导者在分子生物学和棉布衰老研究的副总裁。当许多人认为衰老“刚刚发生的事,”肯扬假设科学家可以控制寿命通过改变基因——毕竟,她认为,这就是进化。在1990年代早期,在她的实验室工作的加州大学旧金山分校,她和她的团队能够证明这个理论。他们寿命增加了一倍小蛔虫的秀丽隐杆线虫后部分抑制基因使细胞对激素控制生长和弹性。

“当我在2014年加入棉布我想直接老化在我的实验室研究,并帮助教育社区的逻辑和机械调节衰老,”凯尼恩说。“但当我回到这里,我意识到我可以让药物。”

快进到今天和AbbVie-Calico团队致力于不同生物衰老过程的影响,从炎症激素水平对压力的反应。研究目的明确,凯尼恩说。

”,因为很多疾病都与老化,干预措施,提高健寿和动物的寿命通常减轻这些疾病,”她说。“只要有一种与年龄相关的疾病相关通路,我们可以进入管道和旨在造福两特定病人组,然后也许,最终改善每个人的生活质量。”