Targeting Circadian Clock Dysfunction in Alzheimer's Disease (TClock4AD)

最近在生物钟(CC)方面获得诺贝尔奖的发现为治疗包括阿尔茨海默病(AD)在内的许多疾病的开创性方法奠定了基础。广告是当前公共卫生的优先事项。AD治疗的低成功率放大了患者数量不断增加的人口结构负担。鉴于调控记忆、睡眠和神经退行性变的CC基因改变了AD的表达谱，CC最近已成为新的有效药物的可行治疗靶点。然而，如何发展它们仍然是一个根本性的挑战。“针对阿尔茨海默氏症的昼夜节律紊乱”博士网络(TClock4AD)的提出是为了培养能够通过利用神经生物学、药物化学、药物纳米技术、神经免疫学、大数据、生物信息学和企业家精神来面对这些挑战的新一代研究人员。TClock4AD将利用来自欧盟、英国、以色列、美国和中国的10所顶尖大学、3个研究中心、1家医院、包括中小企业在内的10家非学术机构、一家大型制药公司、一个健康行业协会和一个患者组织的独特专业知识和先进技术。TClock4AD将为15名博士生提供双学位，拥有Triple-I知识/技能、宽广的视野和面向商业的心态。他们的研究活动将围绕5个科学主题展开，以(1)为新的CC候选药物开发新颖的人工智能、针对嵌合体的蛋白质分解和多靶点策略；(2)开发考虑CC的新型药物释放纳米技术；(3)研究创新的体外(干细胞、3D培养)和体内(果蝇)药物，以及用于CC药物临床前验证的器官芯片技术；(4)深入了解AD中CC的潜在分子机制及相关药物在小鼠和线虫模型中的反应；(5)开发创新的生物技术商业模式和开发策略。

Recent Nobel Prize-winning discoveries on the circadian clock (CC) have laid the foundation for ground-breaking approaches to treating many diseases, including Alzheimer's disease (AD). AD is a current public health priority. Amplifying the demographic burden of the rising numbers of patients is the low success rate of AD therapies. Given that CC genes regulating memory, sleep, and neurodegeneration has altered expression profiles in AD, CC has recently emerged as a viable therapeutic target for new effective drugs. However, how to develop them remains a fundamental challenge. The "Targeting Circadian Clock Dysfunction in Alzheimer's Disease" Doctoral Network (TClock4AD) is proposed to create a new generation of researchers able to face such challenges by harnessing neurobiology, medicinal chemistry, pharmaceutical nanotechnology, neuroimmunology, big data, bioinformatics, and entrepreneurship. TClock4AD will exploit unique expertise and advanced technologies at 10 leading universities, 3 research centres, a hospital, 10 non-academic institutions including SMEs, a large pharma company, a Health industry association, and a patient organization across the EU, UK, Israel, USA and China. TClock4AD will deliver double degrees to 15 doctoral candidates, with triple-i knowledge/skills, broad vision and a business-oriented mindset. Their research activities will be structured around 5 scientific themes to (1) develop novel artificial intelligence-, proteolysis targeting chimeras- and multitarget-based strategies for new CC drug candidates; (2) develop novel drug delivery nanotechnologies, which take into consideration CC; (3) investigate innovative in vitro (stem-cells, 3D cultures) & in vivo (Drosophila), as well as organ-on-chip techniques, for preclinical validation of CC drugs; (4) get insight into the molecular mechanisms underlying CC in AD and associated drug response in mice and C. Elegans models; (5) develop innovative biotech business model and exploitation strategies.