This study is a two-arm placebo controlled randomized clinical trial, to assess the effect of a 12-week EGCG intervention on physical frailty compared to placebo in pre-frail older cancer survivors.

开始日期2024-06-28

申办/合作机构

University of Rochester

ChiCTR2400085567 / Suspended早期临床1期IIT

Effect of epigallocatechin gallate on postprandial blood glucose and insulin level

开始日期2024-06-19

申办/合作机构

中国农业大学

NCT06398405 / Recruiting临床2期IIT

Efficacy and Safety of Epigallocatechin-3-gallate, an Important Polyphenolic That Originates From Tea, in Patients With Esophageal Squamous Cancer: A Phase II Trial

The investigators conduct this phase II study to evaluate safety and effectiveness of EGCG in patients with dysphagia. Swallowing-related dysphagia and pain scores were recorded using the numerical rating scale (NRS) daily . Barium meal radiography was utilized to measure the luminal size and the length of the lesion area both before and after a week of EGCG treatment. The scales are translated into Chinese and guides in Chinese are developed instructing how to use the scales and perform the assessments.

开始日期2024-04-22

申办/合作机构

山东省肿瘤医院

100 项与 α-synuclein x APP 相关的临床结果

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100 项与 α-synuclein x APP 相关的转化医学

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0 项与 α-synuclein x APP 相关的专利（医药）

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项与 α-synuclein x APP 相关的文献（医药）

2024-12-01·International Immunopharmacology

Exploring the nexus of cGAS STING pathway in neurodegenerative terrain: A therapeutic odyssey

Review

作者: Gurjeet Singh, Thakur ; Kaur Grewal, Amarjot ; Khan, Heena ; Sharma, Ojashvi

By detecting and responding to cytosolic DNA, the cGAS STING pathway regulates the innate immune responses bymediatinginflammatory reactions and antiviral defense. Thederegulation and modification of this system have been linked to variousneurodegenerative diseases like AD, PD and ALS. Accumulation of tau protein and Aβ aggregates to activate the pathway and releases neuroinflammatory cytokines which accelerates neuronal dysfunction and cognitive impairment as the symptom of AD. Similarly, in PD Alpha-synuclein aggregates activate the cGAS STING pathway and regulate the neuroinflammation and oxidative stress. In ALS, mutation of the genes causes the activation of the pathway which leads to motor neuron degeneration. Alteration of the cGAS STING pathway also leads to mitochondrial dysfunction and impaired autophagy. Preclinical investigations of AD, PD, and ALS animal models showed that STING pathway inhibitors reduced inflammation and improved neurological outcomes and modulators of the cGAS STING pathway may treat these neurodegenerative disorders. In this review we focus on the fact thatneuroinflammation, neuronal dysfunction, and various disease progressions can be treated byaltering the cGAS STING pathway. Understanding the processes and creating specific interventions for this route may offer new treatments for these terrible illnesses.

2024-11-01·Neurochemistry International

Protein aggregation and its affecting mechanisms in neurodegenerative diseases

Review

作者: Wu, Jia nan ; Cai, Jing ; Ren, Reng ; Wu, Jia Nan ; Chen, Tao ; Wu, Junyun

Protein aggregation serves as a critical pathological marker in a spectrum of neurodegenerative diseases (NDs), including the formation of amyloid β (Aβ) and Tau neurofibrillary tangles in Alzheimer's disease, as well as α-Synuclein (α-Syn) aggregates in Parkinson's disease, Parkinson's disease-related dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). A significant proportion of patients with amyotrophic lateral sclerosis (ALS) exhibit TDP-43 aggregates. Moreover, a confluence of brain protein pathologies, such as Aβ, Tau, α-Syn, and TDP-43, has been identified in individual NDs cases, highlighting the intricate interplay among these proteins that is garnering heightened scrutiny. Importantly, protein aggregation is modulated by an array of factors, with burgeoning evidence suggesting that it frequently results from perturbations in protein homeostasis, influenced by the cellular membrane milieu, metal ion concentrations, post-translational modifications, and genetic mutations. This review delves into the pathological underpinnings of protein aggregation across various NDs and elucidates the intercommunication among disparate proteins within the same disease context. Additionally, we examine the pathogenic mechanisms by which diverse factors impinge upon protein aggregation, offering fresh perspectives for the future therapeutic intervention of NDs.

2024-11-01·International Journal of Biological Macromolecules

Present and future use of exosomes containing proteins and RNAs in neurodegenerative diseases for synaptic function regulation: A comprehensive review

Review

作者: Yin, Xiaoping ; Chen, Zhiying ; Li, Chuan ; Yang, Seung Bum ; Liu, Ziying ; Cheng, Lin ; Zhang, Xiaorong ; Qiu, Yuemin ; Xiong, Yinyi ; Shen, Chunxiao ; Cao, Wa

Neurodegenerative diseases (NDDs) are increasingly prevalent with global aging, demanding effective treatments. Exosomes, which contain biological macromolecules such as RNA (including miRNAs) and proteins like α-synuclein, tau, and amyloid-beta, are gaining attention as innovative therapeutics. This comprehensive review systematically explores the potential roles of exosomes in NDDs, with a particular focus on their role in synaptic dysfunction. We present the synaptic pathophysiology of NDDs and discuss the mechanisms of exosome formation, secretion, and action. Subsequently, we review the roles of exosomes in different types of NDDs, such as Alzheimer's disease and Parkinson's disease, with a special focus on their regulation of synaptic function. In addition, we explore the potential use of exosomes as biomarkers, as well as the challenges and opportunities in their clinical application. We provide perspectives on future research directions and development trends to provide a more comprehensive understanding of and guidance for the application of exosomes in the treatment of NDDs. In conclusion, exosomes rich in biological macromolecules, as a novel therapeutic strategy, have opened up new possibilities for the treatment of NDDs and brought new hope to patients.

项与 α-synuclein x APP 相关的新闻（医药）

2024-08-05

·药明康德

穿越血脑屏障！ADC开辟阿尔茨海默病、帕金森病新治疗模式

AC Immune公司日前在阿尔茨海默病协会国际会议（AAIC 2024）上发布了一类新型抗神经退行性疾病候选药物，称为Morphomer抗体偶联药物（morADC）。在肿瘤学中，抗体偶联药物的设计用于以靶向方式选择性杀死肿瘤细胞，而AC Immune的morADC用于神经退行性疾病，结合了Morphomer小分子的高度大脑渗透性与单克隆抗体的靶向特异性，以减少中枢神经系统中病理性聚集蛋白。 morADC能够靶向包括β淀粉样蛋白（Aβ）、Tau和α-突触核蛋白在内的重要靶点，同时允许单一或双重靶向策略（例如，将抗Aβ抗体与抗Tau小分子结合），在单一制剂中提供组合疗法。在临床前研究中，morADC与传统抗体相比，将穿越血脑屏障的能力提高5倍，显著改善了药物在中枢神经系统中的暴露水平。 ▲morADC技术显著改善药物穿越血脑屏障的能力（图片来源：AC Immune公司官网） AC Immune公司表示，这一新治疗模式有望为治疗多种神经退行性疾病提供潜在“first-in-class”和“best-in-class”疗法。参考资料： [1] AC Immune Unveils Novel Therapeutic Antibody Drug Conjugate (ADC) Technology for Improved Efficacy in Neurodegenerative Diseases at AAIC 2024. Retrieved August 2, 2024, from https://www.globenewswire.com/news-release/2024/07/31/2921866/0/en/AC-Immune-Unveils-Novel-Therapeutic-Antibody-Drug-Conjugate-ADC-Technology-for-Improved-Efficacy-in-Neurodegenerative-Diseases-at-AAIC-2024.html 内容来源于网络，如有侵权，请联系删除。

抗体药物偶联物

2024-07-25

·GlobeNewswire-Health Care

Annovis Bio Secures U.S. Patent for Treatment of Acute Traumatic Brain Injury with Buntanetap

July 24, 2024 -- Annovis Bio Inc. (NYSE: ANVS) (“Annovis” or the “Company”), a late-stage clinical drug platform company pioneering transformative therapies for neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), announced today the issuance of a U.S. patent for methods of treating acute traumatic brain injuries (TBI) with its lead drug candidate, buntanetap. In 2016, the Company filed a patent covering the treatment of various nerve insults, including TBI, stroke, and nerve and spinal cord injuries. While these claims were granted in Europe and worldwide, the U.S. Patent and Trademark Office (USPTO) required the claims to be divided into individual patents for each indication. Annovis Bio has now received U.S. Patent No. 12,042,482, which covers methods for treating TBI and preventing nerve cell death with buntanetap. “We are thrilled to achieve this significant milestone for buntanetap,” said Maria Maccecchini, Ph.D., Founder, President, and CEO of Annovis. “Nerve cell death is a common underlying factor in many brain conditions, beyond just Alzheimer’s and Parkinson’s. Our preclinical studies in TBI and stroke animal models have demonstrated buntanetap’s efficacy in preventing cell death and loss of function, and it is our duty to explore its potential benefits for victims of brain trauma, a prevalent issue in the U.S.” This patent significantly strengthens Annovis Bio’s portfolio which includes patents and patent applications covering the use of buntanetap for acute and chronic neurodegenerative diseases as well as mental illnesses. The Company's commitment to addressing a broad range of neurodegenerative [MM1] disorders highlight its innovative approach to restoring brain function and improving patient outcomes. Buntanetap (formerly known as Posiphen or ANVS401) targets neurodegeneration by inhibiting the formation of multiple neurotoxic proteins, including amyloid beta, tau, alpha-synuclein, and TDP43. This improves synaptic transmission, axonal transport, and reduces neuroinflammation. Dysregulation of these pathways has been shown to cause nerve cell degeneration and ultimately nerve cell death. By targeting these pathways, buntanetap has the potential to reverse neurodegeneration in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, thereby aiming to restore brain function and improve the quality of life for patients. Headquartered in Malvern, Pennsylvania, Annovis Bio Inc. is dedicated to addressing neurodegeneration in diseases such as AD and PD. The company’s innovative approach targets multiple neurotoxic proteins, aiming to restore brain function and improve the quality of life for patients. For more information, visit www.annovisbio.com and follow us on LinkedIn, YouTube, and X. The content above comes from the network. if any infringement, please contact us to modify.

2024-07-23

·药明康德

阿尔茨海默病大逆转！毒性蛋白“克星”，全新鼻腔喷剂阻止了认知衰退

当我们谈论起阿尔茨海默病的病理特征时，会想到过度累积的β-淀粉样蛋白（Aβ）形成的斑块。另一方面，神经组织内部大量聚集的病理性tau蛋白也是不容忽视的存在，这些蛋白会形成一些神经纤维缠结，同时还保留有神秘的“种子”传播机制，即从一个病变区域释放病理性的tau蛋白，到新的区域生根发芽形成纤维缠结，严重损伤健康的神经功能。近些年的研究发现，相较于纤维缠结，tau蛋白低聚体具备更强的神经元毒性，阻断这部分蛋白不仅可以恢复小鼠的认知功能，还可以防止tau蛋白“种子”继续传播。而想要实现这一目的，靶向tau蛋白低聚体的抗体疗法是极具潜力的一种策略。不过，正在研究阶段的tau蛋白靶向疗法存在一些亟需解决的问题，比较关键的是如何让抗体顺利突破血脑屏障进入大脑内部，另外还要让抗体不仅仅作用于细胞外的tau蛋白聚集体，还要在细胞内同样起效。最近，来自得克萨斯大学的研究团队带来了全新突破，他们设计出的抗体不仅可以有效识别出有毒性的tau蛋白低聚体，还能进入细胞内部发挥作用。同时，这种抗体能以鼻腔喷雾方式通过鼻-脑通路进入大脑，突破血脑屏障的障碍。接受治疗的病理性小鼠，认知功能可得到有效改善，并且大脑内部的tau蛋白低聚体、神经纤维缠结减少。相关论文已经发表在《科学-转化医学》上。研究将这一新型抗体称作TTCM2，在测试中，他们确认TTCM2只对具有神经毒性的tau蛋白低聚体高度亲和，不会影响健康细胞的tau蛋白单体的正常功能，也不会对Aβ或者α-突触核蛋白产生反应。相较于年轻小鼠，TTCM2的活性在年老小鼠大脑中明显要更加活跃，并且在tau蛋白敲除的小鼠中没有活性。除了特异性靶向病理性tau蛋白，TTCM2还显现出强大的tau蛋白“种子”抑制能力，在特殊的tau蛋白突变细胞系中，TTCM2可以有效减少病理性tau蛋白传播，以及细胞内部的tau蛋白聚集体形成。 ▲TTCM2抗体可以有效识别病理性tau蛋白（图片来源：参考资料[1]）有了这种卓越的tau蛋白对抗能力，剩下要解决的便是将其高效递送到大脑内部。传统的静脉注射容易导致抗体被代谢或被血浆中的酶所清除，抗体也难以穿透血脑屏障。新研究中，作者使用了鼻腔喷雾形式进行抗体递送，为了增强抗体的穿透性，他们额外给抗体添加了一个脂质微团外壳，这可以增强细胞膜的亲和性，帮助抗体穿透鼻粘膜以及神经细胞。 ▲通过特殊脂质包裹和鼻腔递送，抗体可以有效进入大脑和细胞内部发挥作用（图片来源：参考资料[2]）作者发现小鼠在接受鼻腔喷雾TCCM2治疗后，大约3小时内，TTCM2就会广泛地出现在大脑各个区域，包括海马体、皮层、小脑等。同时，神经元细胞内部也能检测到TTCM2的存在，这说明抗体已经进入细胞内部，作者还发现抗体在细胞内的位置往往会与tau蛋白聚集体重叠，这暗示着它会对病理性tau蛋白发挥靶向作用。研究在tau蛋白病理模型小鼠中测试了新疗法的作用，当小鼠在老年阶段初步表现出认知功能障碍时，作者给部分实验小鼠执行了单剂量的鼻腔喷雾治疗。相较于未处理的小鼠，实验小鼠在治疗2周后，在行为测试和迷宫测试的表现就明显更好，治疗可以显著改善小鼠的短期记忆功能障碍。此外，小鼠大脑样本显示，TCCM2治疗降低了tau蛋白低聚体水平，磷酸化tau蛋白、错误折叠tau蛋白都有所减少，这些变化都支持了小鼠认知、记忆功能的改善。值得一提的是，作者尝试在去世的AD患者大脑样本中使用了TTCM2，这些抗体也可以准确识别其中的病理性tua蛋白，也预示着该疗法能对人类发挥相同作用，研究团队正计划进一步推动人类临床试验，验证新疗法的作用。参考资料： [1] Sagar Gaikwad et al, Nasal tau immunotherapy clears intracellular tau pathology and improves cognitive functions in aged tauopathy mice, Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adj5958 [2] A nose for tau. Science Translational Medicine (2024). DOI: 10.1126/scitranslmed.adq6489 内容来源于网络，如有侵权，请联系删除。