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

最近获得诺贝尔奖的关于生物钟（CC）的发现为治疗包括阿尔茨海默病（AD）在内的许多疾病的突破性方法奠定了基础。AD是当前的公共卫生重点。阿尔茨海默病治疗的低成功率加剧了患者数量不断增加的人口负担。考虑到调节记忆、睡眠和神经变性的CC基因改变了AD的表达谱，CC最近成为新的有效药物的可行治疗靶点。然而，如何开发它们仍然是一个根本性的挑战。“针对阿尔茨海默病的生物钟功能障碍”博士网络（TClock4AD）旨在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、生物信息学和创业精神，培养新一代能够应对此类挑战的研究人员。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、一家医院、10家非学术机构（包括中小企业、一家大型制药公司、一家健康产业协会和一家患者组织）的独特专业知识和先进技术。TClock4AD将为15名拥有三级知识/技能、广阔视野和商业导向思维的博士候选人提供双学位。他们的研究活动将围绕5个科学主题进行：(1)为新的CC候选药物开发新的人工智能，蛋白质水解靶向嵌合体和基于多靶点的策略；(2)开发考虑CC的新型纳米给药技术；(3)研究创新的体外（干细胞，3D培养）和体内（果蝇）以及器官芯片技术，用于CC药物的临床前验证；(4)在小鼠和秀丽隐杆线虫模型中深入了解CC在AD中的分子机制以及相关的药物反应；(5)创新生物技术商业模式和开发战略。

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.