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HEДокторантска мрежа2023–2027

TClock4AD · Targeting Circadian Clock Dysfunction in Alzheimer’s Disease

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период
2023-03-01 → 2027-02-28
Финансиране от ЕС
3 811 637 €
Участници
27
Схема
HORIZON-TMA-MSCA-DN-JD

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Накратко на български

Нарушенията в циркадните ритми, като промените в цикъла на сън и будност, се изследват като фактор при болестта Алцхаймер. Това е важно, защото коригирането на тези сбивания може да помогне при лечението на проблеми с паметта и съня.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Targeting Circadian Clock Dysfunction in Alzheimer’s Disease

Dementia is a major problem of our time. Alzheimer's disease (AD), the leading cause of dementia, accounts for 60-80% of cases, affecting 7 million people in the EU. This number is expected to double over the next 20 years as the population ages. Despite being described by psychiatrist Alois Alzheimer over a century ago, a cure for Alzheimer's disease remains elusive. Finding effective drugs has been a near-impossible task for industry and academic drug discovery, well described by the metaphor of the Death Valley. In June 2021, the FDA approved the antibody aducanumab, the first new AD drug in 18 years, although concerns remain about its efficacy, safety and cost. This highlights the urgent need to continue the development of AD drugs and to meet the challenge by exploring new avenues beyond the current mainstream. The 2017 Nobel Prize in Physiology and Medicine was awarded to Michael Young, Michael Rosbash and Jeffrey Hall “for their discoveries into the molecular mechanisms controlling circadian rhythm”. Disruptions in sleep-wake cycles and circadian rhythms are emerging as early symptoms of AD and correlate with an increased risk of dementia. New research suggests that circadian disruption may play a key role in the onset and progression of AD, making the circadian clock (CC) a promising therapeutic target. Addressing circadian dysfunction could help treat memory and sleep problems at all stages of the disease, from prodromal to preventative stages. TClock4AD has been designed to provide an excellent training platform for a critical rethink of Alzheimer's research and development under the breakthrough idea of targeting CC dysfunction. TClock4AD will provide a double degree to 17 PhD students whose research is structured around 5 scientific themes corresponding to 5 work packages (WPs): (1) develop novel artificial intelligence-, proteolysis targeting chimeras- multitarget and photoswitches-based strategies for identifying drug candidates for CC (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 an innovative biotech business model and exploitation strategies.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Recent Nobel Prize-winning discoveries on circadian clock (CC) have laid the foundation for ground-breaking approaches to treat 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 have 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 challenge 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 centers, a hospital, 10 non-academic institutions including SMEs, a large pharma company, a Health industry association, and a patient organization across 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.

Оригинален текст от CORDIS (на английски).

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Данни: CORDIS, © Европейски съюз