University of Santiago de Compostela

WEDNESDAY, Feb. 5, 2025 -- Occupational exposure to noise and/or vibrations is associated with the presence of vertigo , according to a study recently published in the Journal of Clinical Medicine . Inés Sánchez-Sellero, Ph.D., and Andrés Soto-Varela, Ph.D., both from Universidade de Santiago de Compostela in Spain, and colleagues examined the relationship between occupational noise and/or vibration exposure and vertigo. The analysis included 393 patients (193 with Meniere disease, 63 with vestibular migraine, 21 with vestibular neuritis, and 116 with benign paroxysmal positional vertigo), as well as data from the general population. The researchers found that differences in the distribution of occupations between patients with vertigo and the general population were significant (Chi-square, P = 4.065 × e −20 ). Additionally, patients with vertigo had significantly more exposure to noise (Fisher's exact test, P = 2.97 × e −10 ; odds ratio, 2.595) and vibrations (Fisher's exact test, P = 6.23 × e −10 ; odds ratio, 2.722) compared with the control group. Findings were similar for both men and women. "A relationship between occupational exposure to noise and/or vibrations and the presence of vertigo was observed," the authors write. "Protective and preventive measures could help prevent the occurrence of some diseases involving vertigo." Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

为打造全球ADC/RDC未来产业高地，成都医学城拟于2024年4月18日-19日举办首届未来XDC新药大会！大会以“共创偶联药物产业未来”为主题，由同写意策划，安排一场主论坛和九场主题论坛，邀请“政、产、学、研、金、媒”各领域专家，通过“成果发布、主题演讲、热点对话、表彰颁奖、展览展示”五位一体的多元化的组织形式，迸发更多XDC产业新科技、新业态、新模式，构建XDC产业全新生态，触摸医药产业未来脉动。当首款基于CRISPR的疗法Casgevy于去年12月获得FDA批准，用于治疗镰状细胞病（SCD）和β地中海贫血时，CRISPR技术得到了验证。那么，CRISPR是否也能成为治疗神经退行性疾病的重要工具呢？神经退行性疾病的治疗极其困难。正如Er-Kim Pharmaceuticals的首席执行官Cem Zorlular所指出的，大脑有“数十亿个神经元和数万亿个连接”，结构极其复杂，科学家们尚未完全了解。Zorlular继续道：“这种复杂性使得针对大脑特定区域进行治疗具有挑战性。此外，神经退行性疾病通常有很长的潜伏期，这意味着在疾病发作后很多年可能不会出现症状。这种情况使减缓或阻止疾病进展的治疗方法的开发变得复杂。”尽管如此，像CRISPR这样的基因编辑技术仍然具有潜力。Zorlular解释：“这对阿尔茨海默病和帕金森病等神经退行性疾病尤其重要，这些疾病的特征是神经元和神经网络的持续丧失，继而导致运动障碍、认知问题、语言和呼吸困难。”例如，阿尔茨海默病与APP、PSEN1和PSEN2等特定基因的突变有关。CRISPR可以编辑这些基因，有可能解决这些疾病的潜在病因。目前，利用CRISPR技术治疗神经退行性疾病的研究仍处于早期阶段。下文将探讨评估CRISPR如何用于治疗两种最常见的神经退行性疾病（阿尔茨海默病和帕金森病）以及罕见的遗传性疾病亨廷顿病的研究。1两项阿尔茨海默病疗法初探去年，在阿姆斯特丹举行的阿尔茨海默病协会国际会议（AAIC）上，研究人员公布了两种利用CRISPR治疗阿尔茨海默病的方法。这两种方法都研究了基因如何增加患阿尔茨海默病的风险，以及编辑这些基因会如何降低患阿尔茨海默病的风险，或保护大脑免受淀粉样蛋白的积聚，后者被认为是导致阿尔茨海默病的特定原因。第一项研究来自圣地亚哥大学的研究人员。他们开发了一种利用CRISPR靶向淀粉样前体蛋白（APP）的基因编辑策略，APP是一种导致大脑中β-淀粉样蛋白过度生成的蛋白质，最终导致斑块的积聚。APP基因会产生不同的产物，其中一些具有保护作用，而另一些则与病理有关，比如β-淀粉样蛋白。研究旨在减少β淀粉样蛋白的产生，同时增加神经保护作用。研究人员对患有阿尔茨海默病的老鼠进行了实验，他们发现，CRISPR疗法减少了β-淀粉样斑块的和脑炎症标志物的产生，并伴随神经保护的增加，以及行为和神经系统功能的改善。最重要的是，基因编辑没有对健康的小鼠造成任何不良的副作用。与此同时，在第二项研究中，杜克大学的研究人员开发了另一种CRISPR疗法，这次针对的是一种名为APOE-e4的神经退行性疾病的遗传风险因素。遗传这种基因会增加人们罹患阿尔茨海默病的可能性。虽然这种基因的存在并不代表这个人一定会患病，但拥有一个拷贝数的人得这种病的风险会提高2到3倍，而拥有2个拷贝数的人得病的风险要高8到12倍。在这项研究中，研究人员使用了基于CRISPR/dCas9编辑策略的表观基因组治疗平台来降低APOE-e4的水平。研究发现，在阿尔茨海默病患者的iPSC衍生的微型大脑和人源化小鼠模型中，该平台的主要候选基因可降低APOE-e4水平。此外，该方法没有影响其他被认为具有中性或保护作用的APOE变异体的水平。当然，这些研究仍处于非常早期的阶段，但由于最近批准的阿尔茨海默病治疗法可能会导致严重的副作用，因此寻找CRISPR等更多的创新方法来治疗这种神经退行性疾病，至关重要。2用CRISPR治疗帕金森病帕金森病影响一种叫做多巴胺能的神经元，这种神经元位于中脑的黑质区，对自主运动和行为过程起到关键作用。绝大多数帕金森病例为偶发，只有10%来自遗传。错误折叠的ɑ-synuclein蛋白的聚集体，被称为路易小体（Lewy body），它们被认为参与了帕金森病的病理发展，ɑ-synuclein在多巴胺能神经元中大量存在。α-突触核蛋白的表达也与SNCA基因密切相关，SNCA基因是散发性帕金森病最重要的预测位点之一。SNCA基因的Ala53Thr（A53T）突变被认为是早发性帕金森病最突出的危险因素之一。2022年进行的一项研究也表明，使用CRISPR-Cas9系统删除A53T-SNCA基因显著改善了与帕金森病相关的情况，如α-突触核蛋白的过度产生、反应性小胶质细胞增生、多巴胺能神经变性和与帕金森病相关的运动症状。然而，在大多数情况下，与大多数散发性帕金森病例相关的遗传变异尚不清楚，帕金森病进展的分子机制也尚未完全了解。研究帕金森病的潜在机制面临的挑战是可能涉及多种基因突变的复杂性，但这也是CRISPR可以得到充分利用的领域。CRISPR可以帮助筛查帕金森病的遗传变异以确定其病因，并可以有效地用于开发细胞和全生物研究模型来研究帕金森病的表型。例如，匹兹堡大学进行的一项研究利用Synthego（该公司提供了工程细胞和CRISPR试剂盒）的基因组编辑潜力，生产用于治疗帕金森病的NADPH氧化酶（NOX1、NOX2和NOX4）敲除细胞模型。该研究证明了Nox2酶在氧化应激相关的变性中的作用，包括ɑ-突触核蛋白积累，线粒体中蛋白质输入障碍，以及富含亮氨酸重复序列激酶2（LRRK2）的激活。总的来说，CRISPR治疗帕金森病的最大潜力在于基因筛查，而一旦科学家能够更好地了解这种神经退行性疾病的潜在机制后，情况可能会进一步改善。3亨廷顿病，CRISPR下一片天空亨廷顿病是一种由单一突变和异常蛋白质引起的遗传性神经退行性疾病，是CRISPR基因编辑的完美潜在治疗对象。亨廷顿病是由于亨廷顿蛋白（HTT）基因中的三核苷酸（CAG）扩增，导致了亨廷顿蛋白中的氨基酸谷氨酰胺长链。CAG重复序列（≥40）的过度扩增导致亨廷顿病症状的发生。最有潜力、也是最新的CRISPR研究来自去年暨南大学的研究人员对亨廷顿病的研究。他们证明了CRISPR-Cas9编辑可用于纠正HTT的突变，用正常CAG重复取代过渡膨胀。基因疗法被装入AAV载体，通过颅内或静脉注射的方式输注至猪的体内。单次治疗导致突变型亨廷顿蛋白耗竭，神经毒性和相关症状减轻。这项临床前研究非常有前景，有望进入临床试验。另一项概念验证研究来自约翰·霍普金斯大学和加州大学圣地亚哥分校，研究人员利用基于CRISPR的RNA编辑技术证明了，在来自亨廷顿病患者的三个不同诱导多能干细胞（iPSC）中，突变转录显著减少，每个患者都携带不同数量的重复序列。随后在亨廷顿病小鼠模型中进行的体内实验表明，接受治疗的小鼠的运动功能显著改善，这一效果在小鼠中持续了长达8个月，表明了持久的治疗益处。科学家在这项研究中使用基于CRISPR的RNA编辑方法的原因在于，亨廷顿病产生的突变mRNA转录对疾病的发病机制有显著影响，或将可以成为治疗关注的靶点。4需要克服的障碍正如前面提到的，治疗神经退行性疾病很难，尽管CRISPR对其中一些疾病显示出治疗潜力，但业界仍有很长的路要走。Er-Kim Pharmaceuticals的商业运营分析师和基因治疗专家Buse Baran评论说：“科学家们仍然没有完全了解大多数神经退行性疾病背后的机制。由于缺乏认知，他们很难制定针对疾病根源的治疗方法。此外，神经退行性疾病通常影响大脑中很多细胞，这使得针对受影响细胞的靶向治疗具有挑战。”她还补充道，向大脑提供治疗是另一个重大挑战：血脑屏障阻碍了大多数物质进入大脑，因此难以有效地提供治疗。CRISPR是一种相对较新的技术，刚刚才向世界证明了自己的潜力。Baran说，尽管CRISPR具有巨大的潜力，但仍需要进一步开发，围绕脱靶效应的风险、伦理问题、安全性和递送障碍等挑战仍然存在。Baran也指出，Casgevy的获批，以及基于CRISPR的疗法在临床试验中获得的成功（就疗效和安全性而言）将为其他潜在的CRISPR疗法提供积极基础。“CRISPR是一种越来越高效和精确的多功能技术，能够用于治疗很多疾病……随着CRISPR技术有效性和安全性的不断改善，相关疗法获批的可能性也将增加。”随着更多CRISPR疗法在治疗神经退行性疾病中的成功开展，相信在不久的将来，我们将看到许多基于CRISPR的治疗方法进入临床，用于治疗阿尔茨海默病、帕金森和亨廷顿等疾病。参考文献：1.Re-coding the brain：Is CRISPR capable of curing neurodegenerative diseases?；labiotech更多优质内容，欢迎关注↓↓↓

ChatGPT could help to increase vaccine uptake by debunking myths around jab safety, say the authors of a new study. ChatGPT could help to increase vaccine uptake by debunking myths around jab safety, say the authors of a study published in the peer-reviewed journal Human Vaccines and Immunotherapeutics. The researchers asked the artificial intelligence (AI) chatbot the top 50 most frequently-asked Covid-19 vaccine questions. They included queries based on myths and fake stories such as the vaccine causing Long Covid. Results show that ChatGPT scored nine out of 10 on average for accuracy. The rest of the time it was correct but left some gaps in the information provided, according to the study. Based on these findings, experts who led the study from the GenPoB research group based at the Instituto de Investigación Sanitaria (IDIS) -- Hospital Clinico Universitario of Santiago de Compostela, say the AI tool is a "reliable source of non-technical information to the public," especially for people without specialist scientific knowledge. However, the findings do highlight some concerns about the technology such as ChatGPT changing its answers in certain situations. "Overall, ChatGPT constructs a narrative in line with the available scientific evidence, debunking myths circulating on social media," says lead author Antonio Salas, who as well as leading the GenPoB research group, is also a Professor at the Faculty of Medicine at the University of Santiago de Compostela, in Spain. "Thereby it potentially facilitates an increase in vaccine uptake. ChatGPT can detect counterfeit questions related to vaccines and vaccination. The language this AI uses is not too technical and therefore easily understandable to the public but without losing scientific rigor. "We acknowledge that the present-day version of ChatGPT cannot substitute an expert or scientific evidence. But the results suggest it could be a reliable source of information to the public." In 2019, the World Health Organisation (WHO) listed vaccine hesitancy among the top 10 threats to global health. During the pandemic, misinformation spread via social media contributed to public mistrust of Covid-19 vaccination. The authors of this study include those from the Hospital Clinico Universitario de Santiago which the WHO designated as a vaccine safety collaborating center in 2018. Researchers at the center have been exploring myths around vaccine safety and medical situations that are falsely believed to be a reason not to get vaccinated. These misplaced concerns contribute to vaccine hesitancy. The study authors set out to test ChatGPT's ability to get the facts right and share accurate information around Covid vaccine safety in line with current scientific evidence. ChatGPT enables people to have human-like conversations and interactions with a virtual assistant. The technology is very user-friendly which makes it accessible to a wide population. However, many governments are concerned about the potential for ChatGPT to be used fraudulently in educational settings such as universities. The study was designed to challenge the chatbot by asking it the questions most frequently received by the WHO collaborating center in Santiago. The queries covered three themes. The first was misconceptions around safety such as the vaccine causing Long Covid. Next was false contraindications -- medical situations where the jab is safe to use such as in breastfeeding women. The questions also related to true contraindications -- a health condition where the vaccine should not be used -- and cases where doctors must take precautions e.g. a patient with heart muscle inflammation. Next, experts analyzed the responses then rated them for veracity and precision against current scientific evidence, and recommendations from WHO and other international agencies. The authors say this was important because algorithms created by social media and internet search engines are often based on an individual's usual preferences. This may lead to 'biased or wrong answers', they add. Results showed that most of the questions were answered correctly with an average score of nine out of 10 which is defined as 'excellent' or 'good'. The responses to the three question themes were on average 85.5% accurate or 14.5% accurate but with gaps in the information provided by ChatGPT. ChatGPT provided correct answers to queries that arose from genuine vaccine myths, and to those considered in clinical recommendation guidelines to be false or true contraindications. However, the research team does highlight ChatGPT's downsides in providing vaccine information. Professor Salas, who specializes in human genetics, concludes: "Chat GPT provides different answers if the question is repeated 'with a few seconds of delay'. "Another concern we have seen is that this AI tool, in its present version, could also be trained to provide answers not in line with scientific evidence. "One can 'torture' the system in such a way that it will provide the desired answer. This is also true for other contexts different to vaccines. For instance, it might be possible to make the chatbot align with absurd narratives like the flat-earth theory, deny climate change, or object to the theory of evolution, just to give a few examples. "However, it's important to note that these responses are not the default behavior of ChatGPT. Thus, the results we have obtained regarding vaccine safety can be probably extrapolated to many other myths and pseudoscience."