Bulbo-Spinal Atrophy, X-Linked

家庭最初的矛盾可能也是由此而起，但随着疾病的进展加重，他们连最基本的劳动能力都丧失殆尽……来源 | 医脉通神经科作者 | 王明月第一节：两对夫妇日复一日，科室每天都在上演着不同，却相似的故事。就在这方寸之地，足不出户，就能领略世间百态、人情冷暖。夫妻本是同林鸟，大难临头各自飞。人性本就自私，丈夫为了前途抛妻弃子，妻子因为丈夫无能而一脚踹开，另觅高枝的故事不胜枚举。病房里的5床和6床是“同病相怜”的两个患者，一个叫章擎天，一个叫章一柱，乍一听好似兄弟，“擎天一柱”一个成语对半分开便是二者的姓名。但其实二人在住院之前是从未相识的陌路人。章擎天的妻子叫张开凤，章一柱的妻子叫李开凤，这对蛇蝎妇人将丈夫弃之医院后便不管不顾，4-5天才到医院一次。跟丈夫短暂的相处期间，要么只字不语，要么恶言相向。章擎天和章一柱都是因为肌肉萎缩住院的。除了肌肉萎缩，二人还有一个共同的毛病，就是不能行房事，家庭最初的矛盾可能也是由此而起，但随着疾病的进展加重，他们连最基本的劳动能力都丧失殆尽，更不用提所谓的男女之事。至于为什么不离婚， 外人怎会知道，推测可能是男方家里还有值得她们等待的东西吧。两位患者的子女也随母亲来过医院一次，五官相貌与其父毫无相似之处，两位妇人是否有外遇，也只有她们自己心知肚明。第二节：一眼识病两位患者最初曾拟诊过运动神经元病，医生也曾说过他们可能没有数年可活。这个消息对于二位妻子而言，或许不是坏事，心中窃喜也未曾可知。然而，她俩可能高兴太早了，3-5年过去了，她们的丈夫居然还活着。看着两个废物在家里，令她们鄙夷生厌，索性就丢到医院，眼不见心不烦，并且坚决要求医生不做检查、不能用药，即便用药，也用最便宜的。医院的床位费每天就20块钱，而且把丈夫送进医院，街坊邻里也就没了七嘴八舌指责的理由，她们这个算盘打的真是精明。医院不是收容所，尽管二位妇人算盘打得精明，医生却不会任由其牵着鼻子走。既然住院，该做的检查就不能少，如若不想治疗，那么确诊之日就是出院之时。“王老师，你把话说得这么满，如果不能确诊怎么办？”实习医生周凤有点担心问。“是啊，我们要给自己留有余地才好。”实习医生白皎附和。“放心，这两个病人，一个是肯尼迪病，一个是强直性肌营养不良。如果我猜错了，请你们吃饭。”主治医生王小鹏自信满满。“肌电图一旦做完，诊断就可以八九不离十，但是若再让他们花几千块钱基因确诊，估计不用我们赶出院，这两位妻子也会把丈夫推走。”王小鹏又说。“其实那两个患者也挺可怜的。”周凤轻叹。“是啊，但是这两种病一旦确诊，也没有有效的治疗方法。医院的床位有限，医疗资源还是需要更合理、更有价值的分配。”王小鹏说。“王老师，你为什么这么笃定，这两个患者是肯尼迪病和强直性肌营养不良呢？”白皎问。王小鹏一笑，说道：“我先卖个关子，这个就当作你们两个今天晚上的作业，明天上班告诉我答案。”第三节：闻道有先后经过一晚上的熬夜苦读，第二日清晨的白皎、周凤已经做好了充分的准备，洋洋得意的神态溢于言表，她们现在也掌握了“一眼识病”的本领，心想：“其实也不过如此，闻道有先后而已。”还没等王小鹏开口，两个姑娘便开始自告奋勇的抢答。“章擎天是肯尼迪病，章一柱是强直性肌营养不良。从外观讲，章擎天有乳房的异常发育，且肌肉的萎缩分布在近端，尤其是三角肌萎缩的明显；而章一柱颜面部颞肌萎缩明显，太阳穴处凹陷，是典型的斧头脸，这在教科书里有详细的描述......”周凤讲。“还有章擎天的舌肌萎缩明显，但却只有轻度的言语含糊，也没有明显的吞咽困难，这种舌肌和咽喉肌的分离现象也是肯尼迪病的特点之一；另外章一柱的秃顶、白内障也都是强直性肌营养不良的常见表现。”白皎性子急，还没等周凤把话说完，就开始插嘴。“别急，这不是比赛，挨个说。周凤你还有什么补充的？”王小鹏说。“我和白皎今天早晨来的比较早，又重新看了一遍这两个患者的病历，重新做了一遍体查。”周凤一边说，一边把病历打开，“章擎天的肌酶高于正常(300U），肌酶轻中度升高,这也是肯尼迪病的一个特点，正因为如此，有时容易误诊为肌病。还有章一柱叩诊有肌球，这是肌强直的有力证据。”“对，还有性功能障碍在两种疾病中出现的概率均不低。”白皎补充道。“这两个患者一开始均被误诊为运动神经元病，如果做肌电图，二者的鉴别点是什么？”王小鹏又抛出一个问题。两个姑娘四目相对，一时难以作答。王小鹏也理解，二人均未系统的学习过肌点图，这个问题确实有点朝纲了。“我告诉你们吧，你们目前只需记住一句话：肯尼迪病的肌电图有感觉受累，强直性肌营养不良的肌电图有肌强直放电，这些在运动神经元病的肌电图上都没有。”王小鹏看着两个姑娘满脸涨红，心有不忍，索性把答案说出。“姜还是老的辣，王老师您要是练过嫁衣神功就好了，这样就可以把内力传我们一点，自己看书实在太辛苦了。”白皎又开始调侃。“别闹了，我这不是每天都在给你们输送内力吗！快，你们跑个腿，到肌电图室问问，这两个患者的肌电结果出来没有。”王小鹏说。肌电图的结果正如王小鹏所料。其实很多典型疾病，只要见过一例，就不会忘记，下次若再遇到，几乎都是手到擒来。并非老师高明，确实是闻道有先后，如是而已。第四节：遁形无踪很多人以为医生是一群呆呆傻傻的人，书读的越多，越是愚钝。其实这完全是曲解，医生每天面对各种悲欢离合，观看各色人性表演，家属的心思，一眼便可看清。事态完全按照王小鹏预定的轨道进行，家属坚决拒绝进一步完善几千块钱的基因检测，说没钱了，要求出院，从此音讯全无，消失于茫茫人海。知识点：我把以前写的两篇随笔放在这里，希望能加深大家对肯尼迪病和强直性肌营养不良的认识。1. 肯尼迪病患者四肢近端无力，肌酶1000多，考虑肌病，查肌电图却是神经源性损害，再仔细查体才发现舌肌的萎缩，肌病一般是不累及舌肌的，患者雄激素受体基因CAG重复60次，确诊肯尼迪病。临床中肯尼迪病也容易和运动神经元病混淆。肯尼迪病是X连锁隐性遗传，一般只有男性患病，而运动神经元病则是男女均可患病；肯尼迪病累及四肢近端为主，而运动神经元病远端为主；肯尼迪病舌肌萎缩却不伴有饮水呛咳和构音障碍，这种舌肌和咽喉肌的分离现象，在进行性延髓麻痹中是没有的；运动神经元病不会有感觉受累，而肯尼迪病的肌电图感觉神经可以受累；肯尼迪病可以出现男性乳房发育等表现，运动神经元病没有。肯尼迪病可以出现三角肌和肱二头肌分离现象，往往三角肌受累更严重，就像舌肌和咽喉肌分离。当然不管是肯尼迪病还是运动神经元病都没有特效的治疗方法，虽然肯尼迪病进展慢一些，预后好一些，所以发现下运动神经元表现的患者，首先还是要想到可治疗的疾病，如多灶性运动神经病，进行免疫球蛋白的治疗，不要盲目过早的下诊断。2. 通道病-发作性无力或强直性肌病地铁乘坐者，当地铁停站，想下车离开时，却突然僵固在原地；进行投篮运动时，投篮后却不能立即奔跑；为啥呢？难道现在社会真的有武林高手，可以隔空点穴。有无隔空点穴的武林高手，暂且不表，先天性肌强直就可以出现上述表现。此外该病还有另外一种表现，叫“热身现象”，就是突然运动时身体像捆了绳子，僵硬无法运动，费劲九牛二虎之力勉强运动一会，就像绳子突然解开，脱离束缚。先天性肌强直是一种氯离子通道病，有常显的Thomsen型和常隐的Becker型，由于肌肉不自主的强直放电，就像一个人整天在健身房锻炼，骨骼肌异常发达，跟肌营养不良的假性肥大有天壤之别，后者是外强中干，大部分有脂肪填充，而强直性肌病确是真正发达的骨骼肌。先天性副肌强直，虽然只有一字之别，但却没有“热身现象”，运动可以加重肌强直，此外寒冷也可以明显加重肌肉僵直，患者往往主诉用冷水洗脸后眼睛睁不开。先天性副肌强直是一种钠离子通道病，眼睑闭合性强直（睁眼困难）是钠离子通道病相对特异性表现。此外高钾性周期性麻痹也是一种钠离子通道病，也叫钾恶化性肌强直，补钾可以诱发加重其肌强直的发作，常伴有痛性肌强直，这时可能要跟McArdle病相鉴别（表现为运动后的痛性肌强直和肌红蛋白尿），McArdle病有second wind现象，肌痛后短暂休息可减轻症状，并可继续运动。先天性肌强直、先天性副肌强直、钾恶化性肌强直等疾病与强直性肌营养不良的区别在于：强直性肌营养不良有肌萎缩，而它们没有。本文节选自医脉通神经科经典系列医学微小说“《屌丝医生王小鹏》系列”，欢迎关注医脉通神经科，点此可查看本系列第一季经典医学故事全22章。责编｜阿泰封面图来源｜视觉中国“现在好好工作，将来有的是时间玩！”信了这话的医生，这辈子要遭老罪了该退休就退休，给年轻人腾位置！张文宏最新发声引热议，年轻医生：说出了我的心声医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。☟戳这里，更有料！

BOSTON--( BUSINESS WIRE )-- Nido Biosciences (Nido Bio), a clinical stage company developing precision medicines for debilitating neurological diseases, today announced a new publication in Neurology ® , the medical journal of the American Academy of Neurology, titled “ Functional Outcome Measures to Optimize Drug Development in Spinal and Bulbar Muscular Atrophy .” Led by Nido’s team, researchers from institutions around the world contributed their individual natural history studies that were integrated to generate the largest global SBMA dataset known to date. Through robust analyses of this dataset, highly sensitive functional endpoints were identified that will inform future interventional clinical trials in SBMA. The SBMA functional rating scale (SBMAFRS) and the 6-minute walk test were shown to be the most sensitive outcome measures to monitor progression across a wide range of disease states. Authors also created a modified SBMAFRS with improved performance by including lower limb and trunk measures, while excluding items that contributed less to the overall score. The publication reports results of integrated data from six longitudinal SBMA natural history studies conducted across the United States, Italy, South Korea, United Kingdom, Denmark, and Japan. With data from 278 patients and up to three years of follow-up for the majority of patients, researchers were able to leverage the most comprehensive SBMA dataset worldwide. “The slowly progressive nature of SBMA has been a major obstacle for the development of pharmaceutical treatments, making it clear that we required more sensitive clinical measures and reliable biomarkers for use in clinical trials,” said Vissia Viglietta, M.D., Ph.D., CMO of Nido Bio. “With our lead candidate NIDO-361 currently in Phase 2 clinical trials, research that drives a better understanding of disease evolution metrics, like this publication, allows us to design more efficient clinical studies to assess the impact of therapies for patients suffering from this debilitating disease.” About Spinal and Bulbar Muscular Atrophy (SBMA) and NIDO-361 SBMA, also known as Kennedy’s disease, is a rare inherited X-linked neuromuscular disorder caused by a genetic mutation of the androgen receptor (AR) that results in the loss of skeletal muscle and motor neuron function. Manifesting in men, SBMA causes progressive weakness and wasting of limb, facial and swallowing muscles, which results in impaired mobility, speech, and swallowing. NIDO-361 is a novel small molecule that binds to a distinct site on the androgen receptor and corrects transcriptional dysregulation to restore healthy cell function. About Nido Biosciences Nido Bio is translating today’s neuroscience breakthroughs into tomorrow’s treatments for severe neurological diseases. Leveraging human genetics, we develop precision medicines that address the fundamental biology of disease and restore healthy cell function. NIDO-361, our clinical-stage candidate, is a treatment for Spinal and Bulbar Muscular Atrophy which is a rare and debilitating neuromuscular disease. Additional pipeline programs center around a novel target with the potential to address multiple disease mechanisms and that has broad clinical application across neurodegenerative and peripheral inflammatory diseases. We are creating a sustainable pipeline for the company by utilizing a functional genomics discovery platform based on human cell lines to identify novel targets. Through our approach we seek to transform patient lives in meaningful ways. www.nidobio.com .

BRISBANE, Calif., Nov. 25, 2024 /PRNewswire/ -- ReviR Therapeutics, a pioneering biotechnology company focused on developing novel small molecule RNA modulators for neurogenetic diseases, announced a groundbreaking research grant from the Kennedy's Disease Association (KDA) to advance a therapy for spinal and bulbar muscular atrophy (SBMA), a rare neuromuscular disorder currently lacking effective treatments. SBMA is also known as Kennedy's Disease (KD) named after Dr. William R. Kennedy, who first described the condition. The collaboration aims to identify a small molecule that targets mutant androgen receptor (AR) mRNA splicing and causes selective destruction of the disease-causing mRNA. By modulating mRNA splicing, ReviR aims to develop a potential therapeutic intervention for Kennedy's Disease (KD). "Our proprietary VoyageR platform enables us to identify molecules that induce the destruction of disease mRNA by incorporating a novel pseudo exon, effectively triggering nonsense-mediated decay of the respective mRNA in a manner similar to oligonucleotide therapeutics," said Paul R. August, PhD, Chief Scientific Officer at ReviR Therapeutics. "This breakthrough approach has the potential to significantly reduce toxic disease protein levels and modify disease progression for KD patients." "We are excited to partner with the Kennedy's Disease Association to advance our research efforts and bring hope to the KD community," said Peng Yue, PhD, CEO at ReviR Therapeutics. "By combining our scientific expertise with the KDA's deep understanding of patient needs, we are confident in our ability to develop a transformative therapy for KD." "KDA is excited to partner with ReviR Therapeutics on the potential use of its innovative gene editing technology as a novel therapeutic strategy for Kennedy's Disease. Reducing or eliminating the toxic protein that causes the disease will be life-changing for people living with KD. We look forward to a successful outcome and a long-term relationship with ReviR," said KDA President Terry Thompson, PhD. ReviR's commitment to scientific excellence and patient-centric approach, coupled with the KDA's dedication to supporting individuals with KD, positions this partnership to make a substantial impact on the field of neurodegenerative diseases. The outcomes of this research will not only advance the understanding of disease mRNA regulation but also accelerate the development of innovative therapies for KD. About ReviR Therapeutics ReviR Therapeutics is an emerging biopharmaceutical company focused on the development of RNA-targeting small molecule therapies that modulate the causal genes of diseases, including CNS diseases, cancer, and other rare genetically-defined diseases. ReviR aims to create disease-modifying therapies that are highly specific, efficacious, and safe. Its initial focus is on applying RNA modulation technologies towards genetic diseases with limited or no treatment options. ReviR Therapeutics was founded in 2021 by leaders in computational biology, AI/ML, RNA biology, and drug discovery. The company is headquartered in Brisbane, CA. For more information, visit our website or email [email protected]. About the Kennedy's Disease Association The Kennedy's Disease Association is a non-profit organization dedicated to improving the lives of individuals affected by Kennedy's Disease. The KDA provides support, education, and advocacy for patients and their families, and funds research to accelerate the development of effective treatments for KD. SOURCE ReviR Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED