Anderson Chloe, Bucholc Magda, McClean Paula L, Zhang Shu-Dong
Personalised Medicine Centre, School of Medicine, Altnagelvin Hospital Campus, Ulster University, Glenshane Road, Derry/Londonderry BT47 6SB, UK.
School of Computing, Engineering and Intelligent Systems, Magee Campus, Ulster University, Northland Road, Derry/Londonderry BT48 7JL, UK.
Biomolecules. 2023 Dec 21;14(1):11. doi: 10.3390/biom14010011.
Alzheimer's disease (AD) is a complex neurodegenerative condition that is characterized by the build-up of amyloid-beta plaques and neurofibrillary tangles. While multiple theories explaining the aetiology of the disease have been suggested, the underlying cause of the disease is still unknown. Despite this, several modifiable and non-modifiable factors that increase the risk of developing AD have been identified. To date, only eight AD drugs have ever gained regulatory approval, including six symptomatic and two disease-modifying drugs. However, not all are available in all countries and high costs associated with new disease-modifying biologics prevent large proportions of the patient population from accessing them. With the current patient population expected to triple by 2050, it is imperative that new, effective, and affordable drugs become available to patients. Traditional drug development strategies have a 99% failure rate in AD, which is far higher than in other disease areas. Even when a drug does reach the market, additional barriers such as high cost and lack of accessibility prevent patients from benefiting from them. In this review, we discuss how a stratified medicine drug repurposing approach may address some of the limitations and barriers that traditional strategies face in relation to drug development in AD. We believe that novel, stratified drug repurposing studies may expedite the discovery of alternative, effective, and more affordable treatment options for a rapidly expanding patient population in comparison with traditional drug development methods.
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，其特征是β-淀粉样蛋白斑块和神经原纤维缠结的积累。虽然已经提出了多种解释该疾病病因的理论，但该疾病的根本原因仍然未知。尽管如此，已经确定了一些增加患AD风险的可改变和不可改变的因素。迄今为止，只有八种AD药物获得了监管批准，包括六种对症药物和两种疾病修饰药物。然而，并非所有药物在所有国家都有供应，新型疾病修饰生物制剂的高成本使很大一部分患者无法使用。预计到2050年，目前的患者人数将增加两倍，因此必须为患者提供新的、有效的和负担得起的药物。传统的药物开发策略在AD中的失败率为99%，远高于其他疾病领域。即使一种药物确实进入市场，高成本和缺乏可及性等额外障碍也会阻碍患者从中受益。在本综述中，我们讨论了分层医学药物重新利用方法如何解决传统策略在AD药物开发方面面临的一些局限性和障碍。我们认为，与传统药物开发方法相比，新颖的分层药物重新利用研究可能会加快为快速增长的患者群体发现替代的、有效的和更实惠的治疗选择的速度。
