Chopade Puja, Chopade Neha, Zhao Zongmin, Mitragotri Samir, Liao Rick, Chandran Suja Vineeth
Bob Jones High School Madison Alabama USA.
Department of Pharmaceutical Sciences, College of Pharmacy University of Illinois at Chicago Chicago Illinois USA.
Bioeng Transl Med. 2022 Aug 3;8(1):e10367. doi: 10.1002/btm2.10367. eCollection 2023 Jan.
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.
阿尔茨海默病（AD）和帕金森病（PD）是最常见的神经退行性疾病，仅在美国就影响着数百万人，每年花费数十亿美元。尽管在开发治疗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一种能有效减缓、抑制或治愈神经退行性变的治疗方法。为了更好地了解AD和PD治疗的当前前沿疗法，我们对这两种主要神经退行性疾病在临床试验过程中的过去和当前治疗策略进行了综述。我们简要回顾了目前美国食品药品监督管理局批准的疗法，然后探讨了随着时间推移，在疾病干预的治疗机制、给药途径、递送载体的使用以及结果测量等变量方面，“药物”和“生物制剂”疗法在各个临床阶段的临床试验趋势。然后，我们展示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，转向旨在抑制疾病进展根本原因的抗聚集、抗炎、抗氧化和再生策略。我们还强调了所研究的“生物制剂”疗法类型的不断演变分布，以及AD和PD治疗递送载体使用不足的情况仍在缓慢增加但依然严重。最后，我们简要讨论了治疗AD和PD的新型临床前策略。总体而言，本综述旨在对AD和PD疗法的临床情况进行简要概述，以便更好地了解该领域过去的治疗策略以及当前方法的演变，从而为未来如何有效治疗AD和PD提供更好的信息。
