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日本名古屋大学在肯尼迪病小鼠治疗研究上的最新研究成果

病友 黑—阿米其推荐一篇日本研究人员最新的研究成果。现发布如下:   Therapeutic Target and Drug for Spinal and Bulbar Muscular Atrophy (SBMA)                                                  Dr.Masahisa KatsunoInhibitors against a new therapeutic target molecule improved the body weight, grip power, performance on the rotarod task and lifespan of SBMA mouse model.Core Benefits.This therapy could be the first specific treatment for SBMA..It could be also applied to amyotrophic lateral sclerosis (ALS) treatment.Some of these inhibitors are under clinical development for another indication.Background & Technology   SBMA is a X-linked neurodegenerative disorder resulting in muscle cramps and progressive weakness caused by CAG expansion of the androgen receptor gene. This condition affects fewer than 1 in 150,000 males and there are no effective drugs for SBMA.Our previous studies revealed that testosterone-dependent intra-neuronal accumulation of the pathogenic AR protein plays a crucial role in SBMA. Recently, we identified molecular changes that commonly emerge in both motor neurons and skeletal muscles of a mouse model of SBMA (AR-97Q mice), such as mitochondrial dysfunction and NFκB signal activation (1).   Here, we further performed a comprehensive analysis of signal pathways in the mouse model and identified another important signaling pathway and its target molecule which activation has the strongest impact on the pathophysiology of SBMA. In addition, we also confirmed that existing blood-brain barrier-crossing inhibitors of the target molecule improved cell-viability of SBMA model cells and survival rate of SBMA mice.These drugs have the potential for not only SBMA therapy but also ALS therapy, because our data implies the target has a crucial role on ALS.译文:                                          

                                           脊髓延髓肌萎缩症的治疗靶点及药物                                 
                                Dr.Masahisa Katsuno博士(名古屋大学神经病学系)    

  对抗一种新的治疗靶点分子的某些抑制剂改善了肯尼迪病小鼠模型的体重,抓握能力,转动时的表现及寿命.

核心收益
  这可能是用于治疗肯尼迪病的第一种特殊疗法
  它也有可能用于治疗肌萎缩侧索硬化症(ALS)
  这些抑制剂中的某些正处在对其它症状的临床开发中。

背景与技术 
  SBMA(肯尼迪病)是X连锁的神经退行性疾病,会导致肌肉痉挛和进行性无力.其病因是雄激素受体基因中 CAG的扩展.这种病症会影响少于150,000个男性中的一位,且没有有效的药物. 我们早期的研究揭示,和睾酮相关的致病AR蛋白在神经元内的积累,对肯尼迪病的成因起到了至关重要的作用.最近,我们又鉴定了一种肯尼迪病小鼠模型(AR-97Q小鼠)常出现的运动神经元和骨骼肌两者的分子变化,如线粒体功能障碍和nfκb激活信号的分子变化. 进而,我们进一步进行了小鼠模型中信号通路的综合分析并鉴定了另一个重要的信号通路及其靶分子,它们的活动在SBMA的病理生理学上有着最强的影响.此外,我们还确认了,现有的一些靶分子的血脑屏障交叉抑制剂改善了肯尼迪小鼠模型细胞的细胞活力以及小鼠的存活率.这类药物不仅对肯尼迪病的治疗而且对ALS病(渐冻人病)的治疗都具有潜力.

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