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Alzheimer's and Parkinson's disease therapies in the clinic
Bioengineering & Translational Medicine ( IF 7.4 ) Pub Date : 2022-08-03 , DOI: 10.1002/btm2.10367
Puja Chopade 1 , Neha Chopade 1 , Zongmin Zhao 2 , Samir Mitragotri 3, 4 , Rick Liao 3, 4 , Vineeth Chandran Suja 3, 4
Affiliation  

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative diseases, affecting millions and costing billions each year in the United States alone. Despite tremendous progress in developing therapeutics that manage the symptoms of these two diseases, the scientific community has yet to develop a treatment that effectively slows down, inhibits, or cures neurodegeneration. To gain a better understanding of the current therapeutic frontier for the treatment of AD and PD, we provide a review on past and present therapeutic strategies for these two major neurodegenerative disorders in the clinical trial process. We briefly recap currently US Food and Drug Administration-approved therapies, and then explore trends in clinical trials across the variables of therapy mechanism of disease intervention, administration route, use of delivery vehicle, and outcome measures, across the clinical phases over time for “Drug” and “Biologic” therapeutics. We then present the success rate of past clinical trials and analyze the intersections in therapeutic approaches for AD and PD, revealing the shift in clinical trials away from therapies targeting neurotransmitter systems that provide symptomatic relief, and towards anti-aggregation, anti-inflammatory, anti-oxidant, and regeneration strategies that aim to inhibit the root causes of disease progression. We also highlight the evolving distribution of the types of “Biologic” therapies investigated, and the slowly increasing yet still severe under-utilization of delivery vehicles for AD and PD therapeutics. We then briefly discuss novel preclinical strategies for treating AD and PD. Overall, this review aims to provide a succinct overview of the clinical landscape of AD and PD therapies to better understand the field's therapeutic strategy in the past and the field's evolution in approach to the present, to better inform how to effectively treat AD and PD in the future.

中文翻译:

阿尔茨海默病和帕金森病的临床治疗

阿尔茨海默病 (AD) 和帕金森病 (PD) 是最普遍的神经退行性疾病,仅在美国每年就影响数百万人,造成数十亿美元的损失。尽管在开发控制这两种疾病症状的疗法方面取得了巨大进展,但科学界尚未开发出能够有效减缓、抑制或治愈神经变性的治疗方法。为了更好地了解当前治疗 AD 和 PD 的治疗前沿,我们回顾了临床试验过程中这两种主要神经退行性疾病的过去和现在的治疗策略。我们简要回顾了目前美国食品和药物管理局批准的疗法,然后探讨了疾病干预治疗机制变量的临床试验趋势,随着时间的推移,“药物”和“生物”疗法的临床阶段的给药途径、运载工具的使用和结果测量。然后,我们介绍了过去临床试验的成功率,并分析了 AD 和 PD 治疗方法的交叉点,揭示了临床试验从针对提供症状缓解的神经递质系统的疗法转向抗聚集、抗炎、抗-旨在抑制疾病进展根本原因的氧化剂和再生策略。我们还强调了所研究的“生物”疗法类型的不断分布,以及用于 AD 和 PD 治疗的运载工具的缓慢增加但仍然严重不足。然后,我们简要讨论治疗 AD 和 PD 的新型临床前策略。总体,
更新日期:2022-08-03
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