作者: Morrison, Randall ; Ashford, Miriam ; Seabrook, Guy ; Finley, Shannon ; Weiner, Michael ; Mackin, R. Scott ; Nosheny, Rachel ; Insel, Philip S. ; Truran, Diana ; Rhodes, Emma ; Mosca, Kenneth ; Camacho, Monica R. ; Narayan, Vaibhav A.

INTRODUCTIONThe objective of this study is to evaluate the reliability and validity of the ReVeRe^TM word list recall test (RWLRT), which uses speech recognition, when administered remotely and unsupervised.METHODSProspective cohort study. Participants included 249 cognitively intact community dwelling older adults. Measures included clinician administered neuropsychological assessments at baseline and unsupervised remotely administered tests of cognition from six time-points over six months.RESULTSThe RWLRT showed acceptable validity. Reliability coefficients varied across time points, with poor reliability between times 1 and 2 and fair-to-good reliability across the remaining five testing sessions. Practice effects were observed with repeated administration as expected.DISCUSSIONUnsupervised computerized tests of cognition, particularly word list learning and memory tests that use speech recognition, have significant potential for large scale early detection and long-term tracking of cognitive decline due to AD.

Alzheimer's Research & Therapy2区 · 医学

The effect of galantamine on brain atrophy rate in subjects with mild cognitive impairment is modified by apolipoprotein E genotype: post-hoc analysis of data from a randomized controlled trial

2区 · 医学

ArticleOA

作者: Barkhof, Frederik ; van der Flier, Wiesje A ; Scheltens, Philip ; Prins, Niels D ; Nye, Jeffrey S ; Fox, Nick C ; Knol, Dirk L ; Brashear, H Robert

AbstractIntroductionThe aim of this investigation was to assess the effect of galantamine, an acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors, on brain atrophy in individuals with mild cognitive impairment (MCI), and to assess effect modification by apolipoprotein E (APOE) genotype.MethodsWe used data from the Galantamine-International-11 (Gal-Int-11) trial, a 24-month, randomized, double blind, placebo-controlled, flexible-dose (16 to 24 mg daily) study in patients with MCI. Brain magnetic resonance imaging (MRI), including a 3-dimensional T1-weighted gradient echo volumetric sequence, was performed at screening and at 24 months. We recorded whole brain and hippocampal volumes, and calculated annual atrophy rates. Linear regression analysis was used to calculate adjusted mean differences in the rate of whole brain and hippocampal atrophy, between MCI patients treated with galantamine and with placebo. Additionally, we performed stratified analyses according to APOE genotype.ResultsData from 364 MCI patients with 24-month MRI data (galantamine, n = 176; placebo, n = 188) were included in the volumetric analysis. Subjects treated with galantamine demonstrated a lower rate of whole brain atrophy compared to those treated with placebo (adjusted mean difference 0.18% per year (95% confidence interval (CI) 0.04; 0.30)). Stratified analyses according to APOE genotype, showed that this effect was confined to patients who carried an APOE ϵ4 allele (adjusted mean difference 0.28% per year (95% CI 0.07; 0.50)). Rates of hippocampal atrophy did not differ significantly between study groups.ConclusionsPatients with MCI who were treated with galantamine demonstrated a lower rate of whole brain atrophy, but not of hippocampal atrophy, over a 24-month treatment period, compared to those treated with placebo. This protective effect of galantamine on whole brain atrophy rate in MCI was only present in APOE ϵ4 carriers.

Nature Microbiology1区 · 生物学

Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans

1区 · 生物学

Article

作者: Mileti, Cassidy J ; Tiemeyer, Michael ; Kim, Kris ; Chen, Wesley G ; Werlang, Caroline A ; Burgos, Ana C ; Aoki, Kazuhiro ; Ribbeck, Katharina ; Tymm, Carly ; Wheeler, Kelsey M

Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic colonization¹. In the oral cavity, saliva containing the mucins MUC5B and MUC7 forms a pellicle that coats the soft tissue and teeth to prevent infection by oral pathogens, such as Streptococcus mutans². Salivary mucin can interact directly with microorganisms through selective agglutinin activity and bacterial binding^2-4, but the extent and basis of the protective functions of saliva are not well understood. Here, using an ex vivo saliva model, we identify that MUC5B is an inhibitor of microbial virulence. Specifically, we find that natively purified MUC5B downregulates the expression of quorum-sensing pathways activated by the competence stimulating peptide and the sigX-inducing peptide⁵. Furthermore, MUC5B prevents the acquisition of antimicrobial resistance through natural genetic transformation, a process that is activated through quorum sensing. Our data reveal that the effect of MUC5B is mediated by its associated O-linked glycans, which are potent suppressors of quorum sensing and genetic transformation, even when removed from the mucin backbone. Together, these results present mucin O-glycans as a host strategy for domesticating potentially pathogenic microorganisms without killing them.

280

项与 Johnson & Johnson Innovation LLC 相关的新闻（医药）

2024-10-31

·医药观澜

环形RNA疗法在中国申报临床，环码生物研发

▎药明康德内容团队报道 10月30日，中国国家药监局药品审评中心（CDE）官网公示，环码生物申报的HM2002注射液临床试验申请获得受理。根据环码生物公开资料，这是该公司研发的一款创新环形RNA（circRNA）药物，也是专门为“治疗性血管新生”打造的全新基因治疗药物。截图来源：CDE官网环形RNA是一种在哺乳动物细胞中天然存在的RNA。它们通过RNA前体的不同剪接方式而生成。环形RNA的结构让它们能够避免被先天免疫系统和核酸外切酶识别，与线性mRNA相比，具有更高的稳定性。此外，环形RNA还在改善生产过程复杂性、提高RNA疗法递送效率等方面具有一定优势。这些特征让环形RNA成为多家初创公司的开发重点。环码生物正是一家专注于环形RNA药物开发的创新型生物技术公司。该公司成立于2021年，其已经完成了多项关键环形RNA技术的开发。该公司成立以来先后获得知名投资机构的多轮投资，2023年8月还宣布完成由强生创新-JJDC等领投的数千万美元A轮融资。根据环码生物公开资料介绍，HM2002注射液是一种创新的环形RNA（circRNA）药物。临床前研究结果显示，在心肌梗死动物模型中，HM2002注射液能够促进血管再生，减少梗死和纤维化面积，显著改善心功能，有望为缺血性心脏病的治疗提供新的选择。今年9月，环码生物宣布在接受冠状动脉旁路移植术（CABG）的缺血性心力衰竭患者中完成了HM2002注射液的经心外膜心肌注射给药。环码生物新闻稿表示，这一突破性进展标志着环形RNA类药物正式迈入人体临床试验（first-in-human）的新阶段。这项首次人体研究是一项研究者发起的探索性研究（IIT），试验的主要目标是初步评估在CABG手术中应用HM2002注射液的可行性与安全性，重点监测药物的治疗反应。本次这款HM2002注射液申报临床获得受理，意味着该产品有望于不久后在中国开展注册性临床研究。参考资料： [1] 中国国家药监局药品审评中心官网. Retrieved Oct 30, 2024, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c [2]环形RNA药物-HM2002注射液完成首例患者给药，正式进入临床试验阶段！. Retrieved Sep 25, 2024, from https://mp.weixin.qq.com/s/rsdLrip7Gr3gVW7zua-obw 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

信使RNA基因疗法临床申请核酸药物寡核苷酸

2024-10-29

·药时代

14亿美元！艾伯维加注阿尔茨海默氏症

2024年10月28日，艾伯维宣布斥资14亿美元收购Aliada Therapeutics全部流通股权。 Aliada是一家初创Biotech，成立于2021年，由强生创新JJDC、RA Capital 以及Raven共同孵化，并共同领导了3200万美元的种子资金。成立之初，强生将其创建的MODEL™平台授权给了Aliada，该平台旨在实现高效的BBB（血脑屏障）传输和下游治疗功能。此外，Aliada从杨森引入了一款抗焦谷氨酸淀粉样蛋白β（3pE-Aβ）抗体ALIA-1758。此次艾伯维收购Aliada，便顺利将MODEL™平台以及ALIA-1758收入囊中。 Aliada的CNS管线中拥有多款候选产品，涉及晚期帕金森病（PD）、阿尔茨海默病（AD）、重度抑郁症、精神分裂症以及癫痫。其中，ALIA-1758为Aliada的主要资产，目前正处一期临床试验阶段，旨在评估其安全性、耐受性以及药物动力学。艾伯维首席科学官Roopal Thakkar博士在新闻稿中表示，ALIA-1758是一种潜在’best-in-class’的AD疗法。此外，Aliada的新型BBB穿越技术对公司CNS管线开发完成补充。今年9月，艾伯维宣布旗下PD候选产品Tavapadon的三期临床结果阳性。时隔不久，FDA批准了艾伯维旗下Vyalev（左旋多巴和卡比多巴的前体药物），用于治疗晚期帕金森病成人患者的运动能力波动。顺风之下，艾伯维趁热打铁。10月24日，艾伯维与近20年的合作伙伴Gedeon Richter达成合作，共同发现和开发治疗神经精神疾病的新疗法。此前，双方合作开发了cariprazine（VRAYLAR® / REAGILA®）和ABBV-932。与之对应的是，罗氏今年一年放弃了三款AD候选产品：1月，罗氏向AC Immune退回了两款，包括一款Aβ人源化单克隆抗体Crenezumab，以及另一款Tau单克隆抗体Semorinemab；10月，罗氏向优时比（UCB）退回了一款抗tau抗体bepranemab。当然，艾伯维也并非一帆风顺。在今年二季度财报电话会议上，艾伯维宣布将停止单独开发Aβ抗体ABBV-916。创新药研发就是如此，充满失败的可能，但却不会缺乏对胜利的渴望。封面图来源：123rf 版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 保二冲一，ROCK2抑制剂为何能连续冲击cGVHD治疗前线？恒瑞、君实、亚虹纷纷任命全球BD高管！美知名议员反对《生物安全法案》。。。| 药时代视频首个且唯一！RiboX Therapeutics环形RNA药物获FDA新药临床试验许可点击查看更多精彩！

财报并购临床3期高管变更

2024-10-28

·PipelineReview

AbbVie to Acquire Aliada Therapeutics, Strengthening Focus in Alzheimer's Disease and Neuroscience Pipeline

NORTH CHICAGO, IL and BOSTON, MA, USA I October 28, 2024 I AbbVie (NYSE: ABBV ) and Aliada Therapeutics today announced a definitive agreement under which AbbVie will acquire Aliada, a biotechnology company advancing therapies using a novel blood-brain barrier (BBB)-crossing technology to address challenging central nervous system (CNS) diseases. Aliada’s lead investigational asset utilizing this delivery technology, ALIA-1758, is an anti-pyroglutamate amyloid beta (3pE-Aβ) antibody in development for the treatment of Alzheimer’s disease. “Neuroscience is one of our key growth areas and we are committed to driving innovation in this field to address critical unmet needs for patients living with seriously debilitating neurological diseases such as Alzheimer’s disease,” said Roopal Thakkar, M.D., executive vice president, research and development and chief scientific officer, AbbVie. “This acquisition immediately positions us to advance ALIA-1758, a potentially best-in-class disease-modifying therapy for Alzheimer’s disease. In addition, Aliada’s novel BBB-crossing technology strengthens our R&D capabilities to accelerate the development of next-generation therapies for neurological disorders and other diseases where enhanced delivery of therapeutics into the CNS is beneficial.” “We are pleased to announce the acquisition of Aliada by AbbVie and are excited about AbbVie’s commitment to bringing ALIA-1758 to patients with Alzheimer’s disease. Our proprietary MODEL™ platform has enabled the development of ALIA-1758, a promising step forward in brain delivery of an anti-amyloid antibody therapy,” said Michael Ryan, M.D., chief medical officer at Aliada Therapeutics. “Many promising CNS-targeted therapies fail to reach late-stage trials due to their inability to cross the blood-brain barrier. Our MODEL™ platform addresses this challenge directly, efficiently delivering targeted drugs and potentially transforming how we treat neurological diseases.” Aliada is advancing therapeutic candidates using its Modular Delivery (MODEL™) platform, engineered for high-precision CNS drug delivery. The novel BBB-crossing technology targets transferrin and CD98 receptors (TfR and CD98) which are highly expressed in brain endothelial cells. By engineering highly optimized TfR or CD98 binders, this platform is designed to deliver different types of biological cargoes into the brain, including therapeutic antibodies and genetic medicines such as siRNA. ALIA-1758 utilizes TfR to transport a 3pE-Aβ antibody across the BBB to enable degradation and elimination of amyloid beta plaques, a pathological hallmark of Alzheimer’s disease. This investigational candidate is currently in a Phase 1 clinical trial to assess its safety and tolerability in healthy participants (NCT06406348). Under the terms of the agreement, AbbVie will acquire all outstanding Aliada equity for $1.4 billion in cash, subject to certain customary adjustments. This transaction is expected to close in 4Q2024, subject to regulatory approvals and other customary closing conditions. Advisors AbbVie’s legal advisor was Covington & Burling LLP. Aliada’s exclusive financial advisor was Centerview Partners LLC and Fenwick & West LLP served as legal advisor. About AbbVie AbbVie’s mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people’s lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on LinkedIn, Facebook , Instagram , X (formerly Twitter) , and YouTube. About Aliada Therapeutics Aliada Therapeutics is a biotechnology company focused on addressing delivery challenges in CNS drug development. Aliada is developing next-generation CNS therapeutics with its novel BBB-crossing Modular Delivery (MODEL™) platform technology, which has been shown to efficiently transport diverse therapeutic cargoes into the brain, enhancing effectiveness and addressing the critical need for efficient and versatile large molecule and oligonucleotide delivery. Johnson & Johnson (through its venture capital arm, Johnson & Johnson Innovation – JJDC, Inc.), RA Capital Management, and Raven (RA Capital Management’s incubator) co-founded Aliada and co-led the series seed financing in 2021 to advance the MODEL™ platform created by Johnson & Johnson scientists that was licensed to Aliada at its inception. Further investment was made by OrbiMed and Sanofi Ventures. For more information visit www.aliadatx.com and follow us on LinkedIn and X . SOURCE: AbbVie

并购临床1期引进/卖出寡核苷酸

100 项与 Johnson & Johnson Innovation LLC 相关的药物交易

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100 项与 Johnson & Johnson Innovation LLC 相关的转化医学

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