Science Translational Medicine:意外发现,这种抗癌药可用于治疗杜氏肌营养不良(DMD)

2022-07-04 王聪 生物世界

据统计,全世界每3500-5000名新生男婴中就有一人患此病。患者一般在3-5岁开始发病,最早表现出进行性腿部肌无力,导致不便行走。

杜氏肌肉营养不良症(DMD),是一种 X 染色体隐性遗传病,因此患者多为男性。患者由于编码抗肌萎缩蛋白的基因(Dystrophin)突变,导致无法产生足够的抗肌萎缩蛋白,因此肌肉组织逐渐被脂肪和纤维化组织取代。

据统计,全世界每3500-5000名新生男婴中就有一人患此病。患者一般在3-5岁开始发病,最早表现出进行性腿部肌无力,导致不便行走。通常在12岁时失去行走能力,在青春期开始出现心脏和呼吸无力,并导致严重并发症,通常在20岁-30岁因呼吸衰竭而死亡。

近日,不列颠哥伦比亚大学(UBC)的研究人员在 Science 子刊 Science Translational Medicine 上发表了题为:Metabolic reprogramming of skeletal muscle by resident macrophages points to CSF1R inhibitors as muscular dystrophy therapeutics 的研究论文。

该研究意外发现,种用于癌症治疗的药物 CSF1R 抑制剂,可以增加肌肉弹性,缓解杜氏肌营养不良(DMD)小鼠模型的疾病进展

CSF1R 基因编码集落刺激因子1受体,是一种调控巨噬细胞增殖、分化和功能的细胞因子。CSF1R 抑制剂已被 FDA 批准用于治疗症状性腱鞘巨细胞瘤(TGCT)。

研究团队最初是想探索常驻巨噬细胞在肌肉再生中的作用。研究团队在 DMD 小鼠模型中的研究发现,CSF1R 抑制剂会消耗常驻巨噬细胞,使得肌肉纤维更能抵抗肌营养不良,使用该抑制剂后,对损伤敏感的快肌纤维(IIB 型纤维)开始转变为更能抵抗肌肉收缩引起的损伤的慢肌纤维(IIA/IIX 纤维)。

在几个月内,接受治疗的 DMD 小鼠能够执行体力任务,例如在跑步机上适度跑步,并且比未接受治疗的 DMD 小鼠肌肉损伤更小。

研究团队表示,还需要进一步的研究来确定 CSF1R 抑制剂对人类 DMD 患者是否同样安全有效,多项 CSF1R 抑制剂治疗人类癌症的临床试验表明,CSF1R 抑制剂是安全的,这很可能代表了一种全新的 DMD 治疗方法。

该研究的通讯作者、UBC大学的 Fabio Rossi 教授表示,随着这不是一种治愈 DMD 的方法,但它可以显着延缓疾病进展,从而有望帮助患者更长时间保持活动能力、远离轮椅。而且还可以与其他治疗方法或基因治疗联合使用。

值得一提的是,这并不是 CSF1R 抑制剂首次被用于癌症治疗意外的领域,此前,生物技术公司安立玺荣(Elixiron)就曾将 CSF1R 抑制剂用于阿尔茨海默病的治疗,旨在利用 CSF1R 抑制剂的抗巨噬细胞能力来缓解神经炎症。该疗法目前即将开始2期临床试验。

 

原始出处:

FARSHAD BABAEIJANDAGHI, et al. Metabolic reprogramming of skeletal muscle by resident macrophages points to CSF1R inhibitors as muscular dystrophy therapeutics. SCIENCE TRANSLATIONAL MEDICINE, 29 Jun 2022, Vol 14, Issue 651.

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    2022-09-23 kalseyzl
  3. 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authenticateStatus=null, createdAvatar=, createdBy=d81c2500028, createdName=12498561m32(暂无昵称), createdTime=Sat Oct 15 13:44:11 CST 2022, time=2022-10-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1238367, encodeId=8f0b123836e46, content= ABSK021是和誉医药独立自主研发的一款全新的口服、高选择性、高活性CSF1R小分子抑制剂,也是首个由中国公司独立自主研发并推进临床的高选择性 CSF-1R抑制剂。大量研究表明,阻断CSF1/CSF-1R信号通路可有效调节和改变巨噬细胞功能,并可能治疗多种巨噬细胞相关人类疾病。和誉医药已在美国完成 ABSK021临床Ia期剂量爬坡试验并正在中国与美国同步开展Ib期多队列扩展阶段研究。除TGCT外,和誉医药也在积极探索ABSK021在多种实体瘤中的临床潜力,并与曙方(上海)医药科技有限公司一起探索其在渐冻症等中枢神经系统疾病中的应用。截至本新闻稿刊发日期,中国尚未有高选择性CSF-1R抑制剂获批上市。, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Fri Aug 12 21:49:14 CST 2022, time=2022-08-12, status=1, ipAttribution=), 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createdName=jichang, createdTime=Tue Jul 05 08:44:11 CST 2022, time=2022-07-05, status=1, ipAttribution=)]
    2023-03-12 柳叶一刀
  4. 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createdName=jichang, createdTime=Tue Jul 05 08:44:11 CST 2022, time=2022-07-05, status=1, ipAttribution=)]
    2022-10-28 jeanqiuqiu
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    2022-08-12 病毒猎手

     ABSK021是和誉医药独立自主研发的一款全新的口服、高选择性、高活性CSF1R小分子抑制剂,也是首个由中国公司独立自主研发并推进临床的高选择性 CSF-1R抑制剂。大量研究表明,阻断CSF1/CSF-1R信号通路可有效调节和改变巨噬细胞功能,并可能治疗多种巨噬细胞相关人类疾病。和誉医药已在美国完成 ABSK021临床Ia期剂量爬坡试验并正在中国与美国同步开展Ib期多队列扩展阶段研究。除TGCT外,和誉医药也在积极探索ABSK021在多种实体瘤中的临床潜力,并与曙方(上海)医药科技有限公司一起探索其在渐冻症等中枢神经系统疾病中的应用。截至本新闻稿刊发日期,中国尚未有高选择性CSF-1R抑制剂获批上市。

    0

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    2022-07-05 sunylz
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