A Phase Ib/IIa, Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Patients With Prodromal or Mild to Moderate Alzheimer's Disease

The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of multiple-ascending intravenous (IV) doses of RO7126209 in participants with prodromal or mild to moderate Alzheimer's disease (AD), who are amyloid positive based on amyloid positron emission tomography (PET) scan.

开始日期2021-03-15

申办/合作机构

Hoffmann-La Roche, Inc.

NCT04023994 / Completed临床1期

A Single-Center, Randomized, Adaptive, Investigator/Subject Blind, Single Ascending Dose, Placebo-Controlled Phase I Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Intravenously Administered RO7126209 in Healthy Participants

Study BP41192 is a randomized, adaptive, placebo-controlled parallel group study to investigate the safety, tolerability, immunogenicity and pharmacokinetics of single-ascending intravenous (IV) doses of RO7126209 in healthy participants. RO7126209 is being developed for the treatment of Alzheimer's Disease.

开始日期2019-08-03

申办/合作机构

Hoffmann-La Roche, Inc.

100 项与 TfR1 x APP 相关的临床结果

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100 项与 TfR1 x APP 相关的转化医学

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0 项与 TfR1 x APP 相关的专利（医药）

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项与 TfR1 x APP 相关的文献（医药）

2025-01-01·Colloids and Surfaces B: Biointerfaces

Multifunctional mesoporous nanoselenium delivery of metformin breaks the vicious cycle of neuroinflammation and ROS, promotes microglia regulation and alleviates Alzheimer's disease

Article

作者: Yuan, Xiaoyu ; Chen, Yutong ; Guo, Xian ; Zhang, Li ; Liu, Yanan ; Zhang, Borui ; Jia, Zhi ; Liu, Jie

Clinical trials based on a single molecular target continue to fail, and the adverse effects of Aβ protein aggregation and neuroinflammation need to be solved and treatment of Alzheimer's disease. Herein, by designed a nano-sized flower mesoporous selenium transport carrier (Met@MSe@Tf) with high enzyme-like activity, metformin (Met) was loaded, and transferrin (Tf) was modified to bind to transferrin receptor to promote receptor-mediated transport across the BBB. In the AD lesion environment, with the acidic environment response dissociation, promote the release of metformin by nanoflower to achieve therapeutic effect in the brain lesion site. Metformin, a major anti-diabetic drug in diabetic metabolism, has been found to be a promising new therapeutic target in neurodegenerative diseases. Further studies showed that the metformin drug release from the designed and synthesized transport nanoparticles showed high intrinsic activity and the ability to degrade the substrate involved, especially the degradation of Aβ deposition in the cortex and hippocampus, increased the phagocytosis of microglia, thus relieving neuroinflammation simultaneously. Collectively, in vivo experiments demonstrated that Met@MSe@Tf significantly increased the number of NeuN-positive neurons in the hippocampus of AD mice, promoted neurovascular normalization in the brain, and improved cognitive dysfunction in AD transgenic AD mice. Thus, it provides a preclinical proof of concept for the construction of a highly modular accurate drug delivery platform for Alzheimer's disease.

2024-12-31·mAbs

Single domain antibody-scFv conjugate targeting amyloid β and TfR penetrates the blood–brain barrier and interacts with amyloid β

Article

作者: Sjöström, Elisabet O. ; Dallas, Tiffany ; Syvänen, Stina ; Berglund, Magnus M. ; Faresjö, Rebecca ; Sehlin, Dag ; Eriksson, Jonas

Neurodegenerative diseases such as Alzheimer's disease (AD) pose substantial challenges to patients and health-care systems, particularly in countries with aging populations. Immunotherapies, including the marketed antibodies lecanemab (Leqembi®) and donanemab (Kisunla^TM), offer promise but face hurdles due to limited delivery across the blood-brain barrier (BBB). This limitation necessitates high doses, resulting in increased costs and a higher risk of side effects. This study explores transferrin receptor (TfR)-binding camelid single-domain antibodies (VHHs) for facilitated brain delivery. We developed and evaluated fusion proteins (FPs) combining VHHs with human IgG Fc domains or single-chain variable fragments (scFvs) of the anti-amyloid-beta (Aβ) antibody 3D6. In vitro assessments showed varying affinities of the FPs for TfR. In vivo evaluations indicated that specific VHH-Fc and VHH-scFv fusions reached significant brain concentrations, emphasizing the importance of optimal TfR binding affinities. The VHH-scFv fusions were further investigated in mouse models with Aβ pathology, showing higher retention compared to wild-type mice without Aβ pathology. Our findings suggest that these novel VHH-based FPs hold potential for therapeutic and diagnostic applications in AD, providing a strategy to overcome BBB limitations and enhance brain targeting of antibody-based treatments. Furthermore, our results suggest that a given bispecific TfR-binding fusion format has a window of "optimal" affinity where parenchymal delivery is adequate, while blood pharmacokinetics aligns with the desired application of the fusion protein.

2024-04-01·Journal of Ethnopharmacology

SuanZaoRen decoction alleviates neuronal loss, synaptic damage and ferroptosis of AD via activating DJ-1/Nrf2 signaling pathway

Article

作者: Long, Qinghua ; Zhu, Qihang ; Li, Tong ; Zhao, Binbin ; He, Liling

ETHNOPHARMACOLOGICAL RELEVANCESuanZaoRen Decoction (SZRD), a famous herbal prescription, and has been widely proven to have positive therapeutic effects on insomnia, depression and Alzheimer's disease (AD). However, the anti-AD molecular mechanism of SZRD remains to be further investigated.AIM OF THE STUDYTo elucidate the molecular mechanism of SZRD's improvement in AD's neuronal loss, synaptic damage and ferroptosis by regulating DJ-1/Nrf2 signaling pathway.MATERIALS AND METHODSLC-MS/MS was used to detect the active ingredients from SZRD. APP/PS1 mice was treated with SZRD and a ferroptosis inhibitor (Liproxstatin-1), respectively. Upon the completion of behavioral tests, Nissl staining, FJB staining, Golgi staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were preformed to evaluate the effects of SZRD on neuronal loss, synaptic damage, Aβ deposition. Iron staining, transmission electron microscopy, and iron assay kit was performed to estimate the effects of SZRD on ferroptosis. SOD kit, MDA kit, GSH kit, and GSH/GSSG kit were utilized to measure the oxidative stress levels in the hippocampus. The protein expression of TfR1, FTH1, FTL, FPN1, DJ-1, Nrf2, GPX4, SLC7A11, and ACSL4 were detected by Western blot.RESULTSA total of 16 active ingredients were identified from SZRD extract. SZRD SZRD significantly alleviated learning and memory impairment in APP/PS1 mice. SZRD improved the hippocampal neuronal loss and degenerated neurons in APP/PS1 mice via inhibiting the Aβ deposit. SZRD mitigated the hippocampal synaptic damage in APP/PS1 mice. SZRD inhibited iron accumulation, and alleviated the oxidative stress level in the hippocampus of APP/PS1 mice. Meanwhile, SZRD could up-regulate the protein expression level of FPN1, DJ-1, Nrf2, GPX4 and SLC7A11 in the hippocampus, and inhibit TfR1, FTH1, FTL, and ACSL4 protein expression.CONCLUSIONSZRD alleviated neuronal loss, synaptic damage and ferroptosis in AD via activating DJ-1/Nrf2 signaling pathway.

项与 TfR1 x APP 相关的新闻（医药）

2024-10-29

·艾伯维abbvie

艾伯维收购Aliada Therapeutics，深化阿尔茨海默病及神经科学研发布局

2024年10月28日，艾伯维与Aliada Therapeutics宣布达成最终协议：艾伯维将收购Aliada，一家致力于利用创新血脑屏障（BBB）穿透技术研发针对难治性中枢神经系统（CNS）疾病新型疗法的生物技术公司。利用这一递送技术，Aliada研发的在研药物ALIA-1758，是一种抗焦谷氨酸化β淀粉样蛋白（3pE-Aβ）抗体，该药物目前正积极开发用于治疗阿尔茨海默病。 Roopal Thakkar博士艾伯维研发执行副总裁兼首席科学官神经科学一直是艾伯维的重点发展领域，我们致力于推动该领域的创新，以应对阿尔茨海默病等严重神经系统疾病患者的迫切医疗需求。此次收购使我们能够迅速推进ALIA-1758的研发工作，该药物有望成为阿尔茨海默病治疗领域的佼佼者。此外，Aliada创新的血脑屏障（BBB）穿透技术将显著提升我们的研发能力，加速我们研发针对神经系统疾病及其他需通过改进药物递送至中枢神经系统来治疗疾病的新一代疗法。 Michael Ryan博士 Aliada Therapeutics首席医学官我们很高兴地宣布艾伯维成功收购Aliada，并对艾伯维公司致力于为阿尔茨海默病患者提供ALIA-1758这一创新疗法感到振奋。Aliada自主研发的MODEL™平台推动了ALIA-1758的研发进程，这是抗淀粉样蛋白抗体疗法在脑部递送方面取得的重要进展。许多颇具前景的中枢神经系统（CNS）靶向疗法因无法穿透血脑屏障而止步于后期试验。但我们的MODEL™平台直击这一挑战，实现了靶向药物的有效递送，并有望彻底转变神经系统疾病的治疗方式。根据协议条款，艾伯维将以14亿美元现金收购Aliada所有流通股权，此金额需根据常规调整因素确定。此次交易预计将于2024年第四季度完成，但还需获得监管机构批准，并满足交易惯例中的其他成交条件。 Aliada利用其模块化递送（MODEL™）平台推进候选药物研发进程。该平台专为实现高精度中枢神经系统（CNS）药物递送而设计。这一新型血脑屏障（BBB）穿透技术，精准靶向在脑内皮细胞中高度表达的转铁蛋白（TfR）和CD98受体（CD98）。通过研发高度优化的TfR或CD98结合剂，该平台能够将多种生物载荷递送至大脑，包括治疗性抗体和基因药物，如siRNA。 ALIA-1758通过转铁蛋白受体（TfR）的介导，助力3pE-Aβ抗体穿透血脑屏障（BBB），实现β淀粉样蛋白斑块的降解与清除，这一病理特征是阿尔茨海默病的重要标志。这一创新性的候选药物正处于1期临床阶段，旨在评估其在健康受试者中的安全性与耐受性（NCT06406348）。上下滑动查看更多信息关于艾伯维艾伯维的使命是发现和提供创新药物，解决复杂且棘手的疾病难题和未来的医学挑战。我们不懈努力，凭借在多个关键治疗领域的科研创新为人们的生活带来深远影响，包括免疫学、肿瘤学、神经科学、眼科学、病毒学、胃肠病学，以及艾尔建美学产品组合中的产品和服务。更多关于艾伯维的信息，请访问www.abbvie.com。艾伯维在中国的总部位于上海，专注于在免疫学、肿瘤学、病毒学、眼科学、麻醉学、神经科学和美学等领域为人们发展和提供创新的医疗方案。如欲了解更多关于艾伯维在中国的信息，请浏览艾伯维中文官网www.abbvie.com.cn。

并购引进/卖出siRNA临床1期临床申请

2024-10-29

·医药魔方Pro

14亿美元！艾伯维最新收购，囊获潜在BIC阿尔茨海默病疗法

10 月 28 日，艾伯维与 Aliada Therapeutics宣布达成一项最终协议，根据该协议，艾伯维将以 14 亿美元现金收购 Aliada 的全部流通股权，这是一家旨在利用新型血脑屏障 (BBB) 穿越技术推进疗法，以应对具有挑战性的中枢神经系统 (CNS) 疾病的biotech。这项交易预计将于 2024 年第四季度完成。 Aliada利用这种递送技术的主要研究资产ALIA-1758是一种抗焦谷氨酸淀粉样蛋白β（3pE-Aβ）抗体，这种焦谷氨酸修饰的淀粉样蛋白β也叫pGlu3-Aβ、Aβ (p3-42)、N3pG。在新闻稿中，艾伯维表示ALIA-1758是一款针对阿尔茨海默病的潜在best-in-class疗法。 ALIA-1758利用TfR跨BBB转运3pE-Aβ抗体，以降解和消除β淀粉样蛋白斑块，这是阿尔茨海默病的病理标志。这项候选研究目前正在进行一期临床试验，以评估其在健康参与者中的安全性和耐受性（NCT06406348）。值得注意的是，就在3个月前，艾伯维被外媒披露正在终止开发其自研的Aβ单抗ABBV-916单药治疗阿尔茨海默病的适应症，并将考虑其它方案，包括联合疗法。ABBV-916与ALIA-1758同样靶向3pE-Aβ，而这也正是礼来在今年获批上市的阿尔兹海默病新药donanemab的靶点。 Aliada正在利用其模块化给药（MODEL）平台推进候选疗法，该平台专为高精度中枢神经系统给药而设计。这项新颖的BBB穿越技术以脑内皮细胞高度表达的转铁蛋白和CD98受体（TfR 和 CD98）为靶标。通过设计高度优化的TfR或CD98结合剂，该平台可将不同类型的生物载体送入大脑，包括治疗性抗体和 siRNA等基因药物。 “神经科学是我们的关键增长领域之一，我们致力于推动这一领域的创新，以满足阿尔茨海默病等严重衰弱性神经疾病患者尚未得到满足的关键需求。”艾伯维研发执行副总裁兼首席科学官 Roopal Thakkar 博士表示：“这次收购使我们立即能够推进 ALIA-1758 的发展，这是一种可能成为阿尔茨海默病最佳疾病修饰疗法的新药。此外，Aliada 的新型 BBB 穿透技术也增强了我们的研发能力，使我们能够加快开发治疗神经系统疾病和其他疾病的下一代疗法，在这些疾病中，加强向中枢神经系统输送治疗药物是有益的。” Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

并购siRNA临床2期引进/卖出

2024-10-28

·医药魔方

艾伯维14亿美元收购Aliada，囊获潜在BIC阿尔茨海默病疗法

并购siRNA临床2期引进/卖出