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引用次数: 0
摘要
阿尔茨海默病(AD)正在全球人口中过度蔓延。许多基因已被确定为阿兹海默症的标志。基于这些知识,设计并开展了许多临床试验。人们试图通过靶向这些基因的分子产物来缓解与注意力缺失症相关的病理现象。尽管对 AD 的基因成分有了一定的了解,但许多临床试验都以失败告终,给药物发现之路带来了更大的挑战。因此,本综述旨在通过研究和评论文章,找出正在进行或已退出临床试验的候选药物(thiethylperazine、CT1812、crenezumab、CNP520 和 lecanemab)的局限性。通过对交叉对话途径的深入分析,我们发现了许多干扰因素,这些因素可能会影响thiethylperazine、CT1812、crenezumab和CNP520等候选药物临床试验的成功。虽然这些候选药物已被纳入临床试验,但文献综述显示其存在许多局限性。这些局限性使人们对这些候选药物被纳入临床试验的理由产生了许多疑问。如果事先对临床研究的结果进行细致的评估,可能会在风险较大的临床试验开始时就将其终止。这可以节省时间、金钱和资源。
Alzheimer's disease (AD) is spreading its root disproportionately among the worldwide population. Many genes have been identified as the hallmarks of AD. Based upon the knowledge, many clinical trials have been designed and conducted. Attempts have been made to alleviate the pathology associated with AD by targeting the molecular products of these genes. Irrespective of the understanding on the genetic component of AD, many clinical trials have failed and imposed greater challenges on the path of drug discovery. Therefore, this review aims to identify research and review articles to pinpoint the limitations of drug candidates (thiethylperazine, CT1812, crenezumab, CNP520, and lecanemab), which are under or withdrawn from clinical trials. Thorough analysis of the cross-talk pathways led to the identification of many confounding factors, which could interfere with the success of clinical trials with drug candidates such as thiethylperazine, CT1812, crenezumab, and CNP520. Though these drug candidates were enrolled in clinical trials, yet literature review shows many limitations. These limitations raise many questions on the rationale behind the enrollments of these drug candidates in clinical trials. A meticulous prior assessment of the outcome of clinical studies may stop risky clinical trials at their inceptions. This may save time, money, and resources.
期刊介绍:
The Journal of Basic and Clinical Physiology and Pharmacology (JBCPP) is a peer-reviewed bi-monthly published journal in experimental medicine. JBCPP publishes novel research in the physiological and pharmacological sciences, including brain research; cardiovascular-pulmonary interactions; exercise; thermal control; haematology; immune response; inflammation; metabolism; oxidative stress; and phytotherapy. As the borders between physiology, pharmacology and biochemistry become increasingly blurred, we also welcome papers using cutting-edge techniques in cellular and/or molecular biology to link descriptive or behavioral studies with cellular and molecular mechanisms underlying the integrative processes. Topics: Behavior and Neuroprotection, Reproduction, Genotoxicity and Cytotoxicity, Vascular Conditions, Cardiovascular Function, Cardiovascular-Pulmonary Interactions, Oxidative Stress, Metabolism, Immune Response, Hematological Profile, Inflammation, Infection, Phytotherapy.