Stuttering

Findings offer new insights with potential to inform diagnosis and treatment PHILADELPHIA, Oct. 16, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) announced the results of a new study highlighting significant genetic links in speech and language disorders in children. The findings, published today in the journal Brain, mark the first time that researchers have studied the genetic basis of linguistic differences separately from other conditions. Genetic factors are known to play a role in speech and language disorders, and the researchers hoped their study would bridge a gap in knowledge to better understand this critical area impacting child development. The research was a collaboration between CHOP's Department of Speech-Language Pathology, the Division of Neurology and the Department of Biomedical and Health Informatics (DBHI). "Our findings highlight the intricate relationship between genes and speech and language development," said Jan Magielski, the study's first author and a data scientist within CHOP's Division of Neurology and Department of Biomedical and Health Informatics. "We hope that the novel connections between genetic causes and specific speech and language disorders reported in the study will offer new and innovative possibilities for earlier intervention and personalized treatment plans." In the study, researchers analyzed electronic medical records of more than 52,000 children treated at CHOP to identify and analyze 26 broad speech and language diagnoses. They found that genetic causes play a major role in speech and language disorders, which are diagnosed more frequently in children between the ages of two and five. While conditions like aphasia, characterized by difficulty speaking, and speech apraxia, or trouble making speech movements, were accurately identified, some speech and language disorders were found to be frequently undetected. Most importantly, stuttering is often underreported in medical records. Their innovative data analysis approach allowed researchers to make three crucial observations. First, they found significant variations in the frequency of speech diagnoses, with mixed receptive-expressive language disorder and developmental disorder of speech and language being the most common diagnosis. Second, the authors observed that speech and language disorders have considerable overlap with neurodevelopmental disorders, movement disorders, and epilepsy. Lastly, the researchers noted that distinct speech characteristics can be linked to specific genes and overlap with known neurodevelopmental conditions. The study connected the genes STXBP1, PTEN and CACNA1A with speech and language disorders. Certain variants of STXBP1 were associated with aphasia while variants of the gene MYO7A were linked with delays in speech and language due to hearing loss. Additionally, in a subset of 726 children with whole exome sequencing data, researchers identified rare genetic changes, linking associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9, and UMODL1 with aphasia. "In the future, we anticipate more targeted studies that delve deeper into the genetic landscape of speech disorders," said Joe Donaher, PhD, CCC-SLP, a senior study author and the Research and Academic Program Director at CHOP's Center for Childhood Communication. "Our study results underscore the need for focused investigations, particularly in areas like stuttering, where genetic research has significantly lagged behind other fields." This study was supported by The Hartwell Foundation through an Individual Biomedical Research Award. This study received support from the National Institute for Neurological Disorders and Stroke, and intramural CHOP funds from the Epilepsy NeuroGenetics Initiative (ENGIN). Magielski, et. al. "The clinical and genetic spectrum of paediatric speech and language disorders." Brain. Online October 16, 2024. DOI: 10.1093/brain/awae264. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Kaila M. Revello Children's Hospital of Philadelphia 267-426-6054 [email protected] SOURCE Children's Hospital of Philadelphia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

关注并星标CPHI制药在线 近日，clinicaltrials网站显示，Bionomics启动了BNC210治疗社交恐惧症（简称社恐）的III期研究（AFFIRM-1）。 该研究是一项多中心、随机、双盲、安慰剂对照临床试验（n=332），旨在评估BNC210（225mg）对比安慰剂急性治疗社恐成人患者的疗效和安全性。研究的主要终点为主观焦虑量表（SUDS）评分。 BNC210是Bionomics开发的一款靶向α7烟碱乙酰胆碱受体（α7 nAChR）的负向变构调节剂，正在被开发用于治疗社恐和创伤后应激障碍（PTSD）。2021年12月，BNC210获FDA授予快速通道资格，用于治疗PTSD、其他创伤和压力源相关疾病、急性治疗社恐和其他焦虑相关疾病。 与临床目前使用的安定和其他苯二氮卓类药物以及氟西汀和其他择性5-羟色胺再摄取抑制剂(SSRIs)和5-羟色胺-去甲肾上腺素再摄取抑制剂(SNRIs)相比，BNC210的优势包括：快速起效、不会出现过度镇静、无戒断症状、不会损伤记忆、无药物相互作用。BNC210这一新型口服片剂可迅速吸收并在大约1小时内达到最大血药浓度。        BNC210作用机制        图片来源：Bionomics公司官网 2023年3月，BNC210（225mg或675mg）治疗社恐的II期PREVAIL研究顺利完成。数据显示，相比于安慰剂组，BNC210组患者的SUDS评分未显著改善（评分差异为5.69分，P=0.165），但结果具有临床意义且显示出了BNC210有益于改善社恐患者焦虑症状的趋势。对入组患者进行年龄分层并重新分析后，Bionomics发现BNC210在改善年轻（≤30岁）社恐患者人群的焦虑症状上的有益趋势更明显（评分差异为10.57分，P=0.069）。 社交焦虑障碍（SAD） “社恐”这一词汇，在被广泛的传播、诠释和使用的同时，已然成为一个网络热词。作为“社交恐惧症患者”的简称，它最初来源于一种疾病名称——社交焦虑障碍（Social anxiety disorder），也被称为社交恐惧症，是一种焦虑症，其特征是在一个或多个社会情境中有大量的恐惧，在日常生活的至少某些部分造成相当大的痛苦和能力受损。可能包含一定的身体症状通常包括脸红、出汗过多、 颤抖、心悸和恶心，口吃和语速快可能同时存在，严重时可以构成惊恐发作。 在医学上，日常生活中的害羞和社交恐惧症的不同之处在于：前者在每个人身上都有，但一定时间后会逐渐消失；而后者则是需要治疗的病症。和害羞不同，社交恐惧症是一种对难堪和出丑的极其强烈的或令人身心疲惫的恐惧感。 SAD 发病机制复杂，目前研究认为，疾病的发生发展涉及生物和环境等多因素相互作用。有研究发现，在 SAD 患者边缘系统中，参与形成情绪反应（尤其是恐惧反应）的杏仁核过度活跃。而其中与焦虑相关的神经递质如 5-羟色胺、去甲肾上腺素、多巴胺和氨基丁酸（GABA）也存在异常。        SAD 的病因分析        图片来源：丁香园 目前，对 SAD 的一线疗法包括广泛应用于焦虑症治疗的认知行为疗法（CBT）和药物治疗。药物通常包括选择性 5-羟色胺再摄取抑制剂（SSRIs）、5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）、和苯二氮卓类（GABA-A 受体激动剂）药物。 不过，SSRIs 和 SNRIs 起效缓慢，需连续服用数周，且治疗效果有限，而苯二氮卓类药物目前还是一种未经 FDA 批准的超说明书用药。截至目前，还没有针对 SAD 的急性治疗药物获批上市。 全球仅三款在研，PH94B临床3期结果积极 Fasedinol(PH94B)是一款GABAA受体调节剂，其以微克剂量通过鼻腔喷雾给药，无味、起效快（15min内）且使用便利。根据Vistagen公司的官方介绍，区别于当前所有的抗焦虑药物，PH94B的独特性在于激活外周鼻化学感应神经元，触发大脑中抑制恐惧和焦虑的神经回路，而不是直接激活GABA-A受体或者直接作用于大脑的中枢神经系统，因此不需要全身摄取，安全性相对更高。2019年12月，美国FDA授予PH94B快速通道资格，用于按需治疗社交焦虑症。蔼睦医疗拥有该产品在中国、韩国和东南亚地区的开发和商业化权益。2022年1月，PH94B获得中国国家药监局药品审评中心（CDE）临床试验默示许可，拟开发用于成人社交焦虑障碍的焦虑症状，这也是社恐鼻喷剂首次在国内获批临床。        PH94B的作用机制        图片来源：Vistagen官网 去年8月，PH94B鼻喷剂在治疗社交焦虑症（SAD）成人患者的临床3期PALISADE-2试验中达到主要终点。与安慰剂相比，fasedienol组患者主观痛苦单位量表（SUDS）评分显著快速下降。Vistagen在新闻稿中表示，这是美国15年来首个社交焦虑障碍在研疗法在3期试验中获得积极结果。 Vistagen公布的是名为PALISADE-2的多中心、随机双盲、安慰剂对照3期研究，共纳入141例成人患者，旨在评估PH94B治疗社交恐惧症的有效性和安全性。结果显示，试验达到主要疗效终点，与安慰剂相比，PH94B组患者的平均SUDS评分对比安慰剂组显著下降（-13.8分 vs. -8.0分）；此外PH94B组患者的应答率也显著高于安慰剂组（40.6% vs. 18.6%），应答率通过临床整体印象-改善（CGI-I）量表评估，定义为焦虑程度大大降低或焦虑程度低得多的患者比例。安全性方面，试验中PH94B鼻喷剂耐受性良好，未发现重度或严重不良事件。 今年4月，Vistagen宣布启动PALISADE-3临床3期试验，该试验评估其在研fasedienol（PH94B）鼻喷剂用于急性治疗社交焦虑症（SAD）成人患者的疗效与安全性。Vistagen计划在2024年下半年启动另一项相同的3期临床试验PALISADE-4，以推动fasedienol成为首个SAD疗法。 除Fasedinol(PH94B)和BNC210处于临床3期外，目前全球还有两款用于治疗社交焦虑的大麻二酚类药物处于临床阶段。 近日，北美处方药服务提供商EmpowerPharm®公布大麻二酚（CBD）药物治疗社交焦虑障碍的2期临床试验结果。该试验评估了大麻二酚药物的剂量，疗效，安全性和耐受性，结果表明，对于患有中度至重度SAD的一部分患者有效。这些结果将指导进一步的临床研究和3期临床的设计。 EmpowerPharm®基于自纳米乳化药物递送系统（SNEDDS）技术的正在申请专利的药物制剂开发此产品。这是一种处方大麻二酚药丸，有望成为世界上第一种被批准用于治疗社交焦虑症的CBD处方药。 另一款RLS103是一种干粉吸入式大麻二酚（CBD），是一种用于急性治疗社交焦虑症的第一类药物/设备组合产品，使用吸入制剂技术与呼吸动力装置相结合。RLS103有可能在三分钟或更短的时间内为患有社交焦虑症的患者提供即时缓解。 2022年3月30日，开发创新疗法以解决中枢神经系统疾病的制药公司Receptor Life Sciences宣布，美国食品药品监督管理局（FDA）接受了RLS103的新药研究（IND）申请。目前RLS103（吸入、干性） Powder CBD）在患有社交焦虑症 （SAD） 的成年患者中的急性焦虑症的 1b/2a 期临床研究正在进行中。 结语 目前，SAD仍然属于小众的新药开发领域，在国内还是一片空白。目前，焦虑症在国内的患病率已高达4.98%，约有8000万患者。但SAD作为焦虑症中的一个类别，在国内的市场现在很难预估，原因在于，疾病识别率低、治疗率低。目前进展最快的SAD新药fasedienol最终结果还没有出来，更不提真正上市、商业化是在何时，未来仍有很长的路要走。目前已有多款新机制药物在此领域取得了积极进展，春天或许已经到来。 参考来源        1.Vistagen Announces Positive Top-Line Results from Phase 3 PALISADE-2 Trial of Fasedienol(PH94B) Nasal Spray in Social Anxiety Disorder.        2.Tillfors M, Furmark T, Marteinsdottir I, et al. Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study[J]. American journal of psychiatry, 2001, 158(8): 1220-1226.        3.Martin E I, Ressler K J, Binder E, et al. The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology[J]. Psychiatric Clinics, 2009, 32(3): 549-575. END 【智药研习社直播预告】 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

An international research group succeeded in identifying the probable origin of stuttering in the brain. An international research group led by researchers from the University of Turku and Turku University Hospital in Finland has succeeded in identifying the probable origin of stuttering in the brain. Stuttering is a speech rhythm disorder characterised by involuntary repetitions, prolongations or pauses in speech that prevent typical speech production. Approximately 5-10% of young children stutter, and an estimated 1% continue to stutter into adulthood. A severe stutter can have a profound negative impact on the life of the individual affected. "Stuttering was once considered a psychological disorder. However, with further research, it is now understood to be a brain disorder related to the regulation of speech production," says Professor of Neurology Juho Joutsa from the University of Turku. Stuttering may also be acquired as a result of certain neurological diseases, such as Parkinson's disease or a stroke. However, the neurobiological mechanisms of stuttering are not yet fully understood, and where it originates in the brain remains uncertain. The findings from brain imaging studies are partly contradictory, and it is challenging to determine which changes are the root cause of stuttering and which are merely associated phenomena. Stuttering localised in the same brain network regardless of its cause Researchers from Finland, New Zealand, the United States and Canada developed a new research design that could provide a solution to this problem. The study included individuals who had suffered a stroke, some of whom developed a stutter immediately after it. The researchers discovered that although the strokes were located in different parts of the brain, they all localised to the same brain network, unlike the strokes that did not cause stuttering. In addition to people who had suffered a stroke, the researchers used magnetic resonance imaging (MRI) to scan the brains of 20 individuals with developmental stuttering. In these individuals, the stuttering was associated with structural changes in the nodes of the brain network originally identified in relation to causal stroke lesions -- the greater the changes, the more severe the stuttering. This finding suggests that stuttering is caused by a common brain network, regardless of the aetiology (developmental or neurological). The key nodes of the network identified by the researchers were putamen, amygdala and claustrum located deep within the brain, and the connections between them. "These findings explain well-known features of stuttering, such as the motor difficulties in speech production and the significant variability in stuttering severity across emotional states. As major nuclei in the brain, the putamen regulates motor function and the amygdala regulates emotions. The claustrum, in turn, acts as a node for several brain networks and relays information between them," explains Joutsa. The results of the study provide a unique insight into the neurobiological basis of stuttering. Locating stuttering in the brain opens up new possibilities for medical treatment. Researchers hope that in the future, stuttering could be effectively treated, for example, with brain stimulation that can be targeted specifically to the now identified brain network.