AZP2006 (Ezeprogind®): a Promising New Drug Candidate in the Battle Against Neurodegenerative Diseases.

IF 3.6 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-03-27 DOI:10.1002/cmdc.202400891
Philippe Verwaerde, Olivier Defert
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引用次数: 0

Abstract

Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein accumulation. This perspective article explores AZP2006 (INN: Ezeprogind), a novel small molecule targeting the Progranulin (PGRN) and Prosaposin (PSAP) axis to enhance lysosomal health in PSP treatment. AZP2006 stabilizes the PGRN-PSAP complex, improving lysosomal function and reducing tau pathology. Preclinical studies in tauopathy models demonstrated AZP2006's ability to decrease tau hyperphosphorylation, enhance neuronal survival, mitigate neuroinflammation and promote synaptogenesis. Clinical trials have shown AZP2006 to be well-tolerated in healthy volunteers and PSP patients. A Phase 2a study met its primary endpoints, as it provided valuable safety data and even encouraged further investigation of its efficacy in a larger clinical study. An upcoming Phase 2b/3 trial aims to assess long-term safety and efficacy in a larger PSP cohort. AZP2006's mechanism of action strongly suggests potential applications in other tauopathies, including Alzheimer's and Parkinson's diseases. By addressing lysosomal dysfunction and tau pathology, AZP2006 represents a promising disease-modifying approach for PSP and other neurodegenerative disorders.

AZP2006 (Ezeprogind®):抗神经退行性疾病的新候选药物
进行性核上性麻痹(PSP)是一种罕见的以异常tau蛋白积累为特征的神经退行性疾病。这篇前瞻性的文章探讨了一种新的小分子AZP2006 (INN: Ezeprogind),它靶向前颗粒蛋白(PGRN)和Prosaposin (PSAP)轴,以改善PSP治疗中溶酶体的健康。AZP2006稳定PGRN-PSAP复合物,改善溶酶体功能并减少tau病理。tau病模型的临床前研究表明,AZP2006能够降低tau过度磷酸化,提高神经元存活,减轻神经炎症和促进突触发生。临床试验表明,AZP2006在健康志愿者和PSP患者中耐受性良好。一项2a期研究达到了其主要终点,因为它提供了有价值的安全性数据,甚至鼓励在更大的临床研究中进一步研究其有效性。即将进行的2b/3期试验旨在评估更大范围PSP队列的长期安全性和有效性。AZP2006的作用机制强烈提示在其他tau病,包括阿尔茨海默病和帕金森病的潜在应用。通过解决溶酶体功能障碍和tau病理,AZP2006代表了一种有希望的PSP和其他神经退行性疾病的疾病改善方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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