FXN Gene Therapy(Voyager Therapeutics)(FXN Gene Therapy(Voyager Therapeutics)) - 在研适应症：Friedreich共济失调_专利_临床

概要

基本信息

药物类型

基因疗法

别名-

靶点-

作用机制-

治疗领域

神经系统疾病遗传病与畸形内分泌与代谢疾病+ [1]

在研适应症

Friedreich共济失调

非在研适应症-

原研机构

Voyager Therapeutics, Inc.

在研机构

Voyager Therapeutics, Inc.

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 FXN Gene Therapy(Voyager Therapeutics) 相关的临床结果

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100 项与 FXN Gene Therapy(Voyager Therapeutics) 相关的转化医学

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100 项与 FXN Gene Therapy(Voyager Therapeutics) 相关的专利（医药）

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2

项与 FXN Gene Therapy(Voyager Therapeutics) 相关的文献（医药）

Frontiers in Immunology

Fluvoxamine maleate alleviates amyloid-beta load and neuroinflammation in 5XFAD mice to ameliorate Alzheimer disease pathology

Article

作者: Ramajayan, P. ; Kumar, Ajay ; Ahmed, Zabeer ; Sharma, Ankita ; Sandha, Kamalpreet Kaur ; Ahmed, Riyaz ; Singh, Parvinder Pal ; Kaur, Sukhleen ; Ramajayan, P ; Ali, Syed Mudassir ; Sharma, Kuhu

IntroductionAlzheimer pathology (AD) is characterized by the deposition of amyloid beta (Aβ) and chronic neuroinflammation, with the NLRP3 inflammasome playing a significant role. This study demonstrated that the OCD drug fluvoxamine maleate (FXN) can potently ameliorate AD pathology in 5XFAD mice by promoting autophagy-mediated clearance of Aβ and inhibiting the NLRP3 inflammasome. MethodsWe used mice primary astrocytes to establish the mechanism of action of FXN against NLRP3 inflammasome by using various techniques like ELISA, Western blotting, confocal microscopy, Immunofluorescence, etc. The anti-AD activity of FXN was validated in transgenic 5XFAD mice following two months of treatment. This was followed by behavior analysis, examination of inflammatory and autophagy proteins and immunohistochemistry analysis for Aβ load in the hippocampi.ResultsOur data showed that FXN, at a low concentration of 78 nM, induces autophagy to inhibit NF-κB and the NLRP3 inflammasome, apart from directly inhibiting NLRP3 inflammasome in primary astrocytes. FXN activated the PRKAA2 pathway through CAMKK2 signaling, leading to autophagy induction. It inhibited the ATP-mediated NLRP3 inflammasome activation by promoting the autophagic degradation of NF-κB, resulting in the downregulation of pro-IL-1β and NLRP3. The anti-NLRP3 inflammasome effect of FXN was reversed when autophagy was inhibited by either genetic knockdown of the PRKAA2 pathway or pharmacological inhibition with bafilomycin A1. Furthermore, FXN treatment led to improved AD pathology in 5XFAD mice, resulting in significant improvements in various behavioral parameters such as working memory and neuromuscular coordination, making their behavior more similar to that of wild-type animals. FXN improved behavior in 5XFAD mice by clearing the Aβ deposits from the hippocampi and significantly reducing multiple inflammatory proteins, including NF-κB, GFAP, IBA1, IL-1β, TNF-α, and IL-6, which are associated with NF-κB and NLRP3 inflammasome in the brain. Moreover, these changes were accompanied by increased expression of autophagic proteins.DiscussionOur data suggest that FXN ameliorates AD pathology, by simultaneously targeting two key pathological features: Aβ deposits and neuroinflammation. As an already approved drug, FXN holds potential as a candidate for human studies against AD.

Frontiers in Immunology

Fluvoxamine maleate alleviates amyloid-beta load and neuroinflammation in 5XFAD mice to ameliorate Alzheimer disease pathology

Article

作者: Kumar, Ajay ; Ahmed, Zabeer ; Sharma, Ankita ; Ahmed, Riyaz ; Singh, Parvinder Pal ; Sandha, Kamalpreet Kaur ; Kaur, Sukhleen ; Ramajayan, P ; Ali, Syed Mudassir ; Sharma, Kuhu

IntroductionAlzheimer pathology (AD) is characterized by the deposition of amyloid beta (Aβ) and chronic neuroinflammation, with the NLRP3 inflammasome playing a significant role. This study demonstrated that the OCD drug fluvoxamine maleate (FXN) can potently ameliorate AD pathology in 5XFAD mice by promoting autophagy-mediated clearance of Aβ and inhibiting the NLRP3 inflammasome. MethodsWe used mice primary astrocytes to establish the mechanism of action of FXN against NLRP3 inflammasome by using various techniques like ELISA, Western blotting, confocal microscopy, Immunofluorescence, etc. The anti-AD activity of FXN was validated in transgenic 5XFAD mice following two months of treatment. This was followed by behavior analysis, examination of inflammatory and autophagy proteins and immunohistochemistry analysis for Aβ load in the hippocampi.ResultsOur data showed that FXN, at a low concentration of 78 nM, induces autophagy to inhibit NF-κB and the NLRP3 inflammasome, apart from directly inhibiting NLRP3 inflammasome in primary astrocytes. FXN activated the PRKAA2 pathway through CAMKK2 signaling, leading to autophagy induction. It inhibited the ATP-mediated NLRP3 inflammasome activation by promoting the autophagic degradation of NF-κB, resulting in the downregulation of pro-IL-1β and NLRP3. The anti-NLRP3 inflammasome effect of FXN was reversed when autophagy was inhibited by either genetic knockdown of the PRKAA2 pathway or pharmacological inhibition with bafilomycin A1. Furthermore, FXN treatment led to improved AD pathology in 5XFAD mice, resulting in significant improvements in various behavioral parameters such as working memory and neuromuscular coordination, making their behavior more similar to that of wild-type animals. FXN improved behavior in 5XFAD mice by clearing the Aβ deposits from the hippocampi and significantly reducing multiple inflammatory proteins, including NF-κB, GFAP, IBA1, IL-1β, TNF-α, and IL-6, which are associated with NF-κB and NLRP3 inflammasome in the brain. Moreover, these changes were accompanied by increased expression of autophagic proteins.DiscussionOur data suggest that FXN ameliorates AD pathology, by simultaneously targeting two key pathological features: Aβ deposits and neuroinflammation. As an already approved drug, FXN holds potential as a candidate for human studies against AD.

100 项与 FXN Gene Therapy(Voyager Therapeutics) 相关的药物交易

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