National & Kapodistrian University of Athens

这项研究提供了一种一流的药物，并进行了高度选择性消除衰老细胞的临床前概念验证。 称为僵尸细胞（zombie cell）的衰老细胞在诸如癌症、心血管疾病、神经退行性疾病和自身免疫疾病之类的多种年龄相关疾病中发挥着关键作用。 在一项新的研究中，来自邓迪大学和雅典大学的研究人员开发了一个可以有效地靶向和消除衰老细胞的平台，从而阻止它们促进年龄相关疾病的进展。这项突破性的研究发表在Nature Aging杂志上。 论文通讯作者、邓迪大学临床分子病理学主席Vassilis Gorgoulis教授说，“众所周知，随着时间的推移，僵尸细胞会导致与衰老过程相关的严重危及生命的疾病。到目前为止，我们还无法在不对宿主产生副作用的情况下消除这些细胞。这项研究首次为在体外和体内准确消除衰老细胞提供了一种切实可行的工具，从而满足了该领域长期未满足的需求。我们如今开发的这种平台为发现和开发抗击衰老和年龄相关疾病（如癌症）的临床上有意义的化合物铺平了道路。” 衰老细胞之所以被称为僵尸细胞，是因为它们在体内仍然存活，但功能不正常。这些细胞不再能够分裂，会对周围的细胞产生负面影响，而且随着时间的推移，会削弱我们的组织、器官和免疫系统。这随后会导致衰老和疾病。正因为如此，衰老细胞的去除有望促进年龄相关疾病（比如癌症）的治疗。 如果要成功去除衰老细胞，识别衰老细胞是先决条件，但这之前已被证明具有挑战性。当前的衰老细胞裂解药物（senolytics）是一类负责消除衰老细胞的抗癌药物，由于它们会损伤周围的健康细胞和组织，因此无法选择性地靶向这些细胞，从而对患者产生副作用。 mGL392化合物构成胶束状达沙替尼偶联LBD支架，可有效靶向衰老细胞 然而，Gorgoulis教授及其同事们如今能够开发出一种能够有效靶向和消除衰老细胞的senolytic平台，该模型的效率确保了最小的副作用。 邓迪大学医学院医学肿瘤系主任Russell Petty教授表示，随着该平台的验证，该研究有可能改变癌症的未来治疗方法。 他说，“这项研究提供了一种一流的药物，并进行了高度选择性消除衰老细胞的临床前概念验证。因此，它为未来选择性消除人类衰老细胞开辟了可能性，这可能会导致一类全新的抗癌药物的开发，并在其他年龄相关疾病中也有应用。”（生物谷 Bioon.com） 参考资料： Sophia Magkouta et al, Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog, Nature Aging (2024). DOI: 10.1038/s43587-024-00747-4.

AACHEN, Germany--(BUSINESS WIRE)--Protembis, a privately-held emerging cardiovascular medical device company, announced today the establishment of a Scientific Advisory Board (SAB) to provide objective advice and contribute to the strategic plans of the company. Specifically, the SAB will provide overarching scientific and clinical strategic guidance, advise on emerging trends and opportunities, and provide expert counsel on scientific and clinical matters. The SAB will be comprised of four internationally recognized interventional cardiologists, who have made significant contributions to the understanding of the role for cerebral embolic protection (CEP) in transcatheter aortic valve replacement (TAVR): Dr Martin Leon MD, Dr Anita Asgar MD, Dr Samir Kapadia MD, and Dr Nicolas van Mieghem MD. The SAB is chaired by Dr Martin Leon, Professor of Medicine at New York’s Columbia University Irving Medical Center and Chief Innovation Officer and the Director of the Cardiovascular Data Science Center for the Division of Cardiology. Dr. Leon has played a pivotal role in shaping the field of interventional cardiovascular medicine through his involvement in over 50 clinical trials. He has co-authored over 1550 publications and has directed or co-directed over 100 international educational programs focused on interventional cardiology. Dr. Leon's significant contributions to the medical community have been recognized with 10 international career achievement awards, and he has been awarded an honorary degree from the University of Athens. “I have been impressed by the Protembis management and their innovative US pivotal clinical trial design that utilizes MRI endpoints. I am looking forward to collaborating with the other members of the SAB to advise on the technology’s future evolution as the field of TAVR expands into lower risk, asymptomatic, and younger patients,” said SAB Chair Dr Martin Leon. Having recently moved from the Montreal Institute of Cardiology where she was medical director of the structural heart program, Dr Anita Asgar is an associate professor and the medical director for structural and interventional cardiology at Northwestern Medicine in Evanston/Chicago, USA. She has published and co-authored almost 200 scientific papers in peer-reviewed journals. Her research interests include the treatment and management of valvular heart disease and cost-effectiveness analyses. Dr Samir Kapadia is chairman of cardiology in the Robert and Suzanne Tomsich Department of Cardiovascular Medicine in Cleveland. He is the author of more than 80 book chapters in medical textbooks on his specialty interests, and he has authored more than 800 articles in peer reviewed medical journals on his clinical experience. He is editor in chief for the Textbook of Interventional Cardiology. Dr Kapadia has been instrumental in the design and execution of the seminal CEP trials as the Co-Principal Investigator of the Sentinel IDE trial (Boston Scientific, Marlborough, MA, USA) and Principal Investigator of the PROTECTED TAVR Trial. Dr Kapadia is a fellow of the American College of Cardiology, European Society of Cardiology, Society of Vascular Medicine, and a member of the American Heart Association and Society of Thoracic Surgery. Dr Nicolas Van Mieghem is a professor of medicine and the director of interventional cardiology at the Thoraxcenter Erasmus University Medical Center in Rotterdam. He has published and co-authored over 500 scientific papers in peer-reviewed journals. He was the Principal Investigator of the MISTRAL-C European Trial of the Sentinel™ device and has been author or co-author on almost 30 publications specifically in the field of CEP. He is a principal investigator and steering committee member in multiple ongoing international trials evaluating various coronary and transcatheter valve technologies. Dr Van Mieghem is a fellow of the European Society of Cardiology and the American College of Cardiology. “We are pleased to announce the creation of this SAB with such a roster of global recognized thought leaders,” said Protembis Co-Chief Executive Officers Karl von Mangoldt and Conrad Rasmus. “To be able to cooperate closely with the members and to benefit from their extensive clinical and strategic knowledge is a privilege. Their guidance will be critical as we map our strategic path forward.” Protembis is currently enrolling patients in the PROTEMBO Pivotal IDE Trial (NCT05873816), which aims to show that the ProtEmbo® System is superior to contemporary practice in reducing new cerebral lesion volume when assessed by Diffusion-Weighted MRI. The novel trial randomizes ProtEmbo against a hybrid control group: half receiving no CEP and half receiving the Sentinel™ device. The trial is led by Dr Roxana Mehran (Mount Sinai, NY, USA) as the Chair of the Study Executive Committee, with Dr Susheel Kodali (New York Presbyterian Hospital, NY, USA), Dr Raj Makkar (Cedars Sinai, Los Angeles, CA, USA) and Dr Stephan Haussig (Herzzentrum, Dresden, Germany), as the Global Co-Principal Investigators. About Protembis Protembis is a privately-held emerging medical device company that has developed the ProtEmbo® Cerebral Protection System. The company strives to provide a simple and reliable solution to protect patients from brain injury during left-sided heart procedures, improving patient quality of life and reducing overall healthcare costs associated with brain injury. The ProtEmbo® System is currently undergoing clinical investigations.

*仅供医学专业人士阅读参考不久前，奇点糕给大家介绍过，根据2021年全球疾病、伤害和风险因素负担研究（GBD）的统计数据，卒中是仅次于缺血性心脏病和COVID-19的第三大死亡原因，造成了730万死亡，其中最常见的类型是缺血性卒中，高病死率和致残率的特点给患者自身、家庭和公共卫生都带来了沉重的负担。急性缺血性卒中的早诊早治对于降低病死率、保留功能非常重要。《中国急性缺血性卒中诊治指南2023》建议缺血性卒中发病4.5小时内的患者，应按照适应证、禁忌证和相对禁忌证进行严格筛选，尽快给予阿替普酶或替奈普酶静脉溶栓治疗[1]。阿替普酶是一种重组组织型纤溶酶原激活物（rt-PA），也是最常用的溶栓药物之一。替奈普酶作为rt-PA的变构体，是一种较新的溶栓药物，对纤维蛋白的特异性更高，半衰期更长，可单次快速给药[1]。因此，优先选用哪种药物引起了越来越多的讨论。在最近的《神经病学》杂志上，雅典大学的研究团队发表了一项系统性回顾和Meta分析研究，对迄今所有比较阿替普酶和替奈普酶在缺血性卒中发病4.5小时内治疗效果和安全性的随机对照临床试验进行了分析，他们发现，二者的安全性相似，但替奈普酶与3个月时功能恢复极好的可能性显著增加5%，以及残疾评分降低的可能性增加10%有关[2]。研究人员在MEDLINE和Scopus数据库中检索了2024年5月16日前发表的符合要求的论文，以及已发表论文的参考文献和国际会议摘要。分析的主要结局为3个月时的极好的功能结局，定义为改良Rankin量表（mRS）评分≤1（总分0-6，从无症状至死亡，2分为轻度残疾）。次要结局包括3个月时的良好的功能结局，定义为mRS≤2；残疾评分降低，定义为所有mRS维度评分下降≥1；症状性颅内出血，以及全因死亡。mRS评分对照研究共纳入了11项符合要求的临床试验，包含3788例接受替奈普酶和3757例接受阿替普酶治疗的患者，替奈普酶组平均年龄69岁，62%为男性，阿替普酶组平均年龄70岁，60%为男性，两组的平均NIH卒中量表（NIHSS）评分均为11分，平均发病至治疗时间均为158分钟。在主要结局中，与阿替普酶组相比，替奈普酶组3个月时达到极好的功能结局的可能性显著增加5%。次要结局中，与阿替普酶组相比，替奈普酶组3个月时的残疾评分降低的可能性显著增加10%，达到良好的功能结局的可能性增加3%，但统计学意义不显著。在安全性方面，两组的症状性颅内出血率和全因死亡率均没有显著差异。研究的主要结局综上所述，这项系统性回顾和Meta分析研究对迄今为止所有可用的随机临床试验进行了总结，表明在标准时间窗内接受溶栓治疗的急性缺血性卒中患者中，替奈普酶在功能恢复极好和减少残疾方面优于阿替普酶，在功能恢复良好方面没有显著差异，安全性也相似。这些结果与此前对6项真实世界研究的Meta分析[3]和2022年时的一项大型真实世界研究[4]的结果都是一致的。研究人员认为，综合现有证据，在临床实践中，溶栓药物治疗可以由阿替普酶向替奈普酶过渡。参考文献：[1] 中华医学会神经病学分会, 中华医学会神经病学分会脑血管病学组. 中国急性缺血性卒中诊治指南2023[J]. 中华神经科杂志, 2024, 57(06): 523-559.[2] Palaiodimou L, Katsanos A H, Turc G, et al. Tenecteplase vs alteplase in acute ischemic stroke within 4.5 hours: a systematic review and meta-analysis of randomized trials[J]. Neurology, 2024, 103(9): e209903.[3] Katsanos A H, Psychogios K, Turc G, et al. Off-label use of tenecteplase for the treatment of acute ischemic stroke: a systematic review and meta-analysis[J]. JAMA network open, 2022, 5(3): e224506-e224506.[4] Tsivgoulis G, Katsanos A H, Christogiannis C, et al. Intravenous thrombolysis with tenecteplase for the treatment of acute ischemic stroke[J]. Annals of Neurology, 2022, 92(3): 349-357.本文作者丨应雨妍