Background:
Cushing s disease is caused by excess ACTH hormone release by a benign tumor of the pituitary gland. It can lead to decreased quality of life and early death. The current best treatment for Cushing s disease is surgery. If surgery does not work or if the tumor returns, there are no more good treatment options. Vorinostat, which is approved to treat a type of lymphoma, might be a treatment option.
Objective:
To test vorinostat to see if it can kill tumor cells and change the number of hormones released in people with Cushing s disease.
Eligibility:
People ages 18 and older who have Cushing s disease and are scheduled for surgery under protocol 03-N-0164 to remove a tumor in their pituitary gland
Design:
Participants will be screened under protocol 03-N-0164.
Participants will stay in the hospital for 8 days before their surgery.
On the first day, participants will have a physical exam and blood tests. They will have their urine collected for testing all day. They will have an ECG: For this, small metal disks or sticky electrode pads will be placed on their chest to record heart activity.
For the next 7 days, participants will have blood tests and all-day urine collection. They will drink at least 2 liters of fluid per day. They will take the study drug by mouth each morning.
On the eighth day, participants will have their surgery. Leftover tissue will be collected for research.
On the day they are discharged from the hospital, participants will have a physical exam and blood tests.

开始日期2024-12-09

申办/合作机构

National Institute of Neurological Disorders & Stroke

NCT06693284 / Not yet recruiting早期临床1期IIT

A Window of Opportunity Trial of Mirdametinib Plus Vorinostat for NF1 Associated, H3K27 Trimethylation Deficient Malignant Peripheral Nerve Sheath Tumor [MPNST]

This is a single center Phase 0 "window of opportunity" trial for the treatment of newly diagnosed, PRC2 deficient, primary malignant peripheral nerve sheath tumors (MPNSTs) with a short course of the combination of mirdametinib and vorinostat prior to the most appropriate standard of care treatment for their specific tumor (typically localized radiation followed by surgical resection). Four to eight patients, 12 years of age or older and meeting the study's biomarker inclusion criteria, would be enrolled onto this trial. After voluntary written consent (assent with parent consent for minors) the patient undergoes MRI and PET imaging of the tumor and a needle biopsy to collect tumor is performed. Patients with histone H3K27 trimethylation deficient MPNST, as confirmed by immunohistochemistry, receive a single 28-day course of mirdametinib and vorinostat at standard oral dosing for each. At day 26, 27, or 28 the patient returns to clinic for a research visit repeating the baseline MRI and PET imaging and the needle biopsy for tumor tissue.
This ends direct study participation. The patient goes on to the most appropriate standard of care treatment for their MPNST. Information about the subsequent standard of care treatment is collected for the purposes of this study.

开始日期2024-12-01

申办/合作机构

University of Minnesota

NCT05608369 / Not yet recruiting临床2期IIT

A Phase 2 Study of Vorinostat in Combination With Chemoradiation in Patients With Locally Advanced HPV Negative HNSCC

The purpose of this study is to learn more about a drug called Vorinostat (an experimental drug) in combination with chemoradiation. The intention of this study is to learn if this drug is safe for the participants and whether this drug with chemoradiation is able to further increase the clinical efficacy of chemoradiation, which is an approved therapy. The main question it aims to answer is: How may Vorinostat interact with standard chemotherapy and radiation therapy in head and neck cancer? Participants will receive the study drug (Vorinostat) as a pre-treatment, followed by standard chemoradiation.

开始日期2024-12-01

申办/合作机构

The Case Comprehensive Cancer Center

100 项与伏立诺他相关的临床结果

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100 项与伏立诺他相关的转化医学

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100 项与伏立诺他相关的专利（医药）

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3,664

项与伏立诺他相关的文献（医药）

2025-02-01·PLANT SCIENCE

Increase of histone acetylation by suberoylanilide hydroxamic acid enhances microspore reprogramming and expression of somatic embryogenesis transcription factors in Brassica napus

Article

作者: Testillano, Pilar S ; Pérez-Pérez, Yolanda ; Testillano, Pilar S. ; Berenguer, Eduardo ; Carneros, Elena

In vivo, microspores in the anthers follow the gametophytic development pathway, culminating in the formation of pollen grains. Conversely, in vitro, under stress treatments, microspores can be reprogrammed into totipotent cells, initiating an embryogenic pathway that produces haploid and double-haploid embryos, which are important biotechnological tools in plant breeding. There is growing evidence that epigenetic reprogramming occurs during microspore embryogenesis through DNA methylation, but less is known about the role of histone modifications. This study investigates the dynamics of histone acetylation during the two microspore developmental pathways, microspore embryogenesis and pollen development, in Brassica napus. We analyzed histone H3 and H4 acetylation levels, histone acetyltransferase (HAT) activity and expression of HAC5 acetyltransferase using immunofluorescence, enzymatic activity assays, ELISA-like tests, and qPCR. Results showed a decrease in global histone acetylation levels during pollen maturation, correlated with reduced HAT activity and downregulation of the BnHAC5-like gene. In contrast, stress-induced microspore reprogramming led to increased histone acetylation levels, enhanced HAT activity, and upregulation of BnHAC5-like. Treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor widely used in animal research but barely applied to plants, enhanced microspore embryogenesis initiation and proembryo formation, while increased histone acetylation levels. SAHA-treated proembryos showed higher expression than control of key embryogenesis transcription factors BnFUS3, BnAGL15, and BnLEC2, suggesting that histone hyperacetylation facilitates transcriptional activation of essential genes for somatic embryogenesis initiation. These findings provided new insights into the epigenetic regulation of this process and revealed new opportunities with histone epigenetic regulator inhibitors, to improve microspore embryogenesis induction for crop improvement.

2025-02-01·JOURNAL OF COLLOID AND INTERFACE SCIENCE

Bioinspired black phosphorus delivers histone deacetylase inhibitor-induced synergistic therapy for lung cancer

Article

作者: Wu, Dan ; Li, Huan ; Fan, Mingde ; Zhou, Dazhi ; Li, Songpei ; Guan, Xiaoling ; Deng, Xiaohua ; Wu, Yuanyuan ; Zhang, Lingmin ; Tao, Yiwen ; Lin, Yinshan

Lung cancer remains one of the most fatal cancers worldwide, with a high incidence of metastasis and a low 5-year survival rate. Histone deacetylase inhibitors (HDACis) have shown significant potential in lung cancer treatment, but their clinical use is often hindered by poor water solubility, rapid clearance, and systemic toxicity. In this study, we developed a novel therapeutic strategy by camouflaging black phosphorus (BP) with M1 macrophage membranes (MB) and loaded HDACi suberoylanilide hydroxamic acid (SAHA) onto the camouflaged black phosphorus (MB) for targeted lung cancer therapy. The M1 membrane coating enhanced the specificity of the SAHA-loaded black phosphorus toward lung cancer cells. Black phosphorus not only served as a carrier for HDACis but also facilitated photothermal therapy (PTT) through its photothermal conversion capabilities, establishing a highly efficient therapeutic platform. MBS demonstrated strong antitumor activity with minimal systemic toxicity. This multifunctional platform, inspired by biological systems, shows great promise for delivering a wide range of HDACis and offers synergistic therapeutic potential through the combination of photothermal therapy and chemotherapy.

2025-02-01·TISSUE & CELL

The Shh-p38-NFATc1 signaling pathway is essential for osteoclastogenesis during tooth eruption

Article

作者: Huang, Xiaofeng ; Wang, Jiran ; Liu, Jinan ; Jia, Xueting ; Huang, Rui

Tooth eruption, a critical stage in tooth development, is related to osteoclastogenesis. Intraperitoneal injection of Shh agonists into neonatal mice promoted tooth eruption at postnatal day (PN) 15, whereas treatment with the Shh inhibitor (LDE225) suppressed this process. When RAW264.7 osteoclast precursor cells were treated with RANKL, NFATc1 translocated from the cytoplasm to the nucleus and induced cell differentiation into TRAP⁺ osteoclasts; this process was activated by Shh but inhibited by LDE225. Treating RAW264.7 cells with the p38 inhibitor, BIRB796, also inhibited NFATc1 nuclear localization. p-p38 expression in the alveolar bone of PN3 and PN5 mice was decreased by treatment with LDE225, and RAW264.7 cell differentiation was reduced by BIRB796, regardless of treatment with Shh. Furthermore, Shh activated p38 signaling pathway in RAW264.7 cells, while p38 phosphorylation was reduced by LDE225, which ultimately inhibited osteoclast precursor differentiation. Therefore, we concluded that Shh promotes osteoclast precursor differentiation via the p38-NFATc1 signaling pathway.

项与伏立诺他相关的新闻（医药）

2024-12-06

·学术经纬

Cancer Discovery｜儿童急性T淋巴细胞白血病的临床特征与高危突变

撰文 | 尹彤责编 | 周叶斌急性T淋巴细胞白血病（T-ALL）是儿童最常见的血液系统肿瘤之一。其中γδ T-ALL是一个较少研究的亚型，其肿瘤细胞表面表达由γ链和δ链组成的T细胞受体（TCR），约占全部T-ALL病例的10%。既往研究提示，该亚型可能面临更差的治疗效果和更高的复发风险。由于缺乏大规模针对γδ T-ALL的研究，其临床特征和发病机制仍不清楚。虽然近年来通过基因组学研究取得了一些进展，但这些研究纳入的γδ T-ALL病例较少，且缺乏对非编码区等基因组特征的分析，因此亟需进行更全面、深入的研究。近日，以圣裘德儿童研究医院 Charles G. Mullighan 和 Hiroto Inaba 团队牵头的多国联合团队在 Cancer Discovery 发表了题为 Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk 的文章。该研究基于200例γδ T-ALL的临床和基因组数据，揭示了发病年龄<3岁、诱导治疗后MRD≥1%和STAG2/LMO2突变是儿童γδ T-ALL的高危因素，进而筛选了针对此类患者有效的治疗策略。本研究纳入了由13项临床研究组成的多国合作组的200例25岁以下的γδ T-ALL患者，以及1,067例根据治疗方案匹配的非γδ T-ALL对照病例。研究发现，γδ T-ALL患者总体上表现出较差的预后，诊断年龄更小，且治疗后的应答更差，表现为在诱导治疗和巩固治疗后都有更高的微小残留病变（measurable residual disease，MRD）水平，需要进行造血干细胞移植的比例更高，且原发病或治疗副作用造成的死亡率更高。诊断年龄小于3岁的γδ T-ALL患者，其5年无事件生存率（event-free survival，EFS）仅为33%，总生存率（overall survival，OS）仅为49%，显著低于诊断年龄≥3岁的γδ T-ALL患者或非γδ T-ALL患者。此外，诱导治疗结束时（end of induction，EOI），MRD≥1%的患者在所有年龄段的生存率均显著低于MRD<1%的患者。这些数据表明诊断年龄 <3岁和 EOI 时 MRD≥1% 是提示 γδ T-ALL 患儿不良预后的高危因素，因此这些高风险患者可能需要优化的治疗方案。此外，研究发现，γδ T-ALL患者的复发主要局限于骨髓（骨髓复发率高达91.3%），而非γδ T-ALL患者中枢神经系统复发更常见。研究设计和患者临床结局：（A）研究方案，（B）γδ T-ALL患者与非γδ T-ALL患者的生存率对比，（C/D）γδ T-ALL患者中诊断年龄和EOI时MRD水平对生存率的影响结合全基因组测序（whole genome sequencing，WGS）、RNA测序和HiChIP等技术，研究者对γδ T-ALL患者的基因变异进行了分型，并解析了突变导致的疾病机制。γδ T-ALL患者与非γδ T-ALL患者相比具有独特的基因型分布。STAG2/LMO2双突变是γδ T-ALL患者特征性变异之一，所有纳入研究的该亚型γδ T-ALL患儿的诊断年龄都小于3岁，且与其他类型患者相比生存期显著较短。进一步研究表明STAG2/LMO2双突变患者中最常见的变异类型是LMO2::STAG2重排，导致STAG2失活和LMO2过度激活。STAG2是黏着复合物（cohesin complex）的重要组分，参与染色质空间折叠以形成拓扑相关结构域（topologically associating domain，TAD），进而通过增强子-启动子相互作用调控基因正常表达。通过构建STAG2缺失和过表达的细胞模型，并进行RNA-seq和H3K27ac ChIP-seq分析，研究者证明了STAG2失活将导致TAD结构异常，严重破坏T细胞分化相关基因表达，导致白血病的发生。此外，研究还发现了其他γδ T-ALL特异性基因分型，如LMO2-γδ样、超二倍体T-ALL伴重现性染色体增加、TLX3重排和PICALM::MLLT10融合等，这些亚型γδ T-ALL患者具有各自不同的临床特征。 γδ T-ALL基因分型和临床特征：（A）参考所有T-ALL基因组数据对γδ T-ALL进行基因分型，（B）不同基因型在γδ T-ALL与非γδ T-ALL患者中的分布，（D）γδ T-ALL患者不同基因型与诊断年龄的关系，（E）不同基因型γδ T-ALL患者的生存曲线最后，研究者通过高通量药物筛选探索了潜在的治疗策略。PARP抑制剂talazoparib和组蛋白去乙酰化酶抑制剂vorinostat是对STAG2/LMO2 γδT-ALL细胞具有显著杀伤作用的药物，其中PARP抑制剂靶向STAG2失活造成的DNA复制缺陷，使双链DNA断裂积累并诱导细胞死亡。在患者来源的异种移植模型（PDX）中，talazoparib 和 vorinostat 都可以有效地抵抗肿瘤生长。其他有效的药物包括nelarabine和L-门冬酰胺酶等，这些药物都已经被用于T-ALL或其他肿瘤的临床研究或治疗。此发现为高风险的γδ T-ALL患儿提供了一种潜在的精准治疗策略。针对talazoparib（Tal）和vorinostat（Vor）的临床前试验表明两种药物均能够显著抑制PDX肿瘤细胞的生长总之，本研究首次全面探讨了儿童γδ T-ALL的临床特征和基因分型，并揭示了高危突变的致病机制及潜在的治疗策略。研究明确了诊断年龄和MRD水平对患者预后的关键作用，并揭示了高危患儿STAG2失活对染色质结构和基因表达具有深远影响。更重要的是，本研究提出了 PARP 抑制剂等可做为靶向 STAG2/LMO2 亚型的潜在治疗策略，这些成果加深了对儿童γδ T-ALL的认识，也为未来γδ T-ALL患儿的风险分层和个体化治疗开发提供了重要参考。撰文责编制作排版 | Sheila 校对 | uu 延伸阅读儿童T细胞急性淋巴细胞白血病的多组学分析竺晓凡/张英驰团队揭示儿童T-ALL癌细胞克隆演化模式及耐药新机制 *本文由深圳市拾玉儿童公益基金会“儿童肿瘤前沿”团队编译或约稿，文中图表均源引自文献原文。本文著作权归文章作者所有，欢迎个人转发分享，未经允许禁止转载，作者拥有所有法定权利，违者必究。如需转载，请留言或联系shiyu@curekids.cn。本文旨在分享儿童肿瘤科研前沿成果，不是治疗方案推荐。如需获得疾病治疗方案指导，请前往正规医院就诊。 ▼滑动查看更多▼ 原文摘要（Abstract） Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. γδ T-ALL diagnosed in children under 3 years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High-throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by poly(ADP-ribose) polymerase inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric γδ T-ALL. Significance: Patients with acute lymphoblastic leukemia expressing the gamma delta T-cell receptor under 3 years old or measurable residual disease ≥1% at end of induction showed dismal outcomes and should be classified as having high-risk disease. The STAG2/LMO2 subtype was enriched in this very young age group. STAG2 inactivation may perturb chromatin conformation and cell differentiation and confer vulnerability to poly(ADP-ribose) polymerase inhibition. DOI: 10.1158/2159-8290.CD-23-1452 👇点击此处，直达原文

细胞疗法临床结果免疫疗法临床研究信使RNA

2024-11-09

·药明康德

权威榜单：这十位青年科学家正在引领基因编辑技术的未来

▎药明康德内容团队编辑 CRISPR-Cas9技术自问世以来仅十余年间，我们已经见证了基因编辑领域的显著进展。首例基于CRISPR基因编辑技术的药物Casgevy已获批用于治疗镰刀型细胞贫血病（SCD）与输血依赖性β地中海贫血（TDT）患者，同时，针对遗传性疾病和癌症的CRISPR基因编辑疗法的临床试验也在如火如荼地进行中。近日，知名行业媒体STAT发表了一篇文章，评选出10位在基因编辑领域崭露头角的青年才俊。他们的开创性工作不仅推动了基因编辑治疗应用的拓展，也为CRISPR技术在人类健康领域的积极影响增添了新的维度。在今天的文章中，药明康德内容团队将带领大家一同了解这些未来之星。点击文末“阅读全文/Read More”，即可查看原文内容。图片来源：123RF Alexis Komor 加州大学圣地亚哥分校（UCSD） Alexis Komor博士目前担任UCSD的助理教授。在她的博士后研究期间，Komor博士成功开发了首个碱基编辑器，这一创新成果在2016年发表于《自然》杂志。自那以后，碱基编辑技术逐渐被应用于临床研究。例如，Beam Therapeutics公司已经开始利用这种技术进行SCD、癌症和α1抗胰蛋白酶缺乏症的临床试验。今年夏天，Komor博士及其在UCSD的团队取得了另一项重大突破，他们开发了四种新型碱基编辑系统，这些多任务编辑器系统被称为MOBE。MOBE允许研究人员同时进行多种类型的单碱基编辑，而且它们之间不会相互干扰，从而降低了错误发生的风险。MOBE编辑器的这一特性对于建立更精确的复杂疾病模型至关重要，并且有望为免疫疗法领域设计出更强效的T细胞。这一进展不仅推动了基因编辑技术的发展，也为未来的医学治疗提供了新的可能性。 Jonathan Gootenberg & Omar Abudayyeh 哈佛大学医学院 Jonathan Gootenberg博士和Omar Abudayyeh博士目前是哈佛大学医学院的研究员。两人在研究生时期就结下了深厚的友谊，并成为了科研搭档。在师从CRISPR基因编辑领域的先驱之一张锋教授期间，他们发现了一种名为Cas13的新酶，并成功将其设计为一种用于编辑RNA的CRISPR系统。几年后，他们又发现了一种更安全的版本，即Cas7-11。基于这些创新成果，他们与张锋教授共同创立了两家公司：Sherlock Biosciences和Proof Diagnostics。这两家公司专注于利用CRISPR技术开发快速诊断测试，为医疗诊断领域带来了革命性的进步。 2022年，他们在麻省理工学院（MIT）麦戈文脑科学研究所（McGovern Institute for Brain Research）担任研究员期间，发明了一种名为PASTE的下一代基因编辑技术，能够实现大段DNA的精准插入，这一突破性成果被《自然》杂志评为“2024年值得关注的七大技术”之一。 Patrick Hsu 加州大学伯克利分校（University of California，Berkeley），Arc研究所（Arc Institute） Patrick Hsu博士是张锋教授的杰出门生之一，目前担任加州大学伯克利分校的助理教授，他同时还是Arc研究所的联合创始人。Hsu博士在将机器智能与生物学相结合的交叉领域走在了前列，致力于挖掘和设计新型CRISPR系统。 2018年，Hsu博士发现了CasRx，这是一种靶向RNA的CRISPR酶，它为治疗由RNA剪接错误引起的疾病（如额颞叶痴呆症）提供了新的治疗途径。今年夏天，他在Arc研究所的研究团队发现了一类新的引导RNA（gRNA），这些gRNA分子有潜力对DNA进行大规模的改变。最近，Hsu博士与Arc研究所的同事们合作，开发了一个生成式人工智能模型，该模型能够设计出前所未有的新型CRISPR系统。尽管这些新系统仍需通过实验测试来验证它们的功能和安全性，但这项工作无疑为基因编辑领域开辟了新的研究方向，为未来探索更多治疗应用提供了可能性。 Alexander Marson Gladstone-UCSF Institute of Genomic Immunology，加州大学伯克利分校 Alexander Marson博士是将CRISPR技术与免疫疗法相结合的先驱之一，他专注于利用基因编辑工具设计T细胞，以增强其对抗血癌的能力。2018年，他开发了一种创新技术，利用脉冲电流将CRISPR元件迅速传递到T细胞中，从而重写其基因序列并赋予其新的功能。此外，他还运用CRISPR筛选技术——这项技术允许研究人员逐一关闭细胞中的每个基因——来识别新的靶点，进而创造出更具肿瘤杀伤能力的T细胞。这些工作极大地推动了体外细胞编辑的速度和精确度。最近，Marson博士的研究团队又取得了新的进展，他们利用抗体和细胞穿透肽的组合，开发出了一种将CRISPR系统有效递送至体内特定细胞类型的方法。Marson博士与Patrick Hsu博士共同创立了Spotlight Therapeutics公司，该公司正在积极推进这些技术，旨在开发出超越现有病毒载体和脂质纳米颗粒的体内基因编辑递送方法，为基因治疗领域带来革命性的变革。 Britt Adamson 普林斯顿大学（Princeton University） Britt Adamson博士目前是普林斯顿大学的助理教授。在她的博士后研究期间，Adamson博士领导了Perturb-seq技术的研究工作——这是一种创新的基因扰动组学测序技术，它将CRISPR基因编辑技术与单细胞测序相结合，使得研究人员能够大规模地研究单个人类基因的功能及其协同工作的方式。 Adamson博士的研究团队发现了一些延缓先导编辑（prime editing）技术的分子障碍。为了克服这些障碍，她与David Liu（刘如谦）教授和Alexander Marson博士合作，开发出了更高保真度的新型先导编辑器版本。这些改进后的编辑器在相关人类细胞中的应用前景广阔，有望为治疗遗传疾病提供新的策略。其中的一些技术升级被《细胞》杂志评为2022年最令人兴奋的细胞生物学研究之一。此外，Adamson博士的实验室还取得了另一项重要成就：他们成为了首个在小鼠胚胎中高效进行先导编辑的实验室。这一成就对于遗传疾病建模和哺乳动物发育研究具有重大意义，为这些领域的研究提供了强大的新工具。 Ben Kleinstiver 麻省总医院（Massachusetts General Hospital） Ben Kleinstiver博士是麻省总医院的助理教授，他专注于利用蛋白质工程技术来扩展CRISPR技术的临床应用。在过去几年中，Kleinstiver博士在将基因编辑技术转化为新型基因药物方面做出了多项重要贡献。 Kleinstiver博士及其团队设计构建了新型CRISPR酶，这种酶能够识别和编辑人类DNA中更多的片段。这一创新是相对于第一代CRISPR系统的重大进步，因为第一代CRISPR系统能够进入并编辑的区域有限，从而限制了其能够解决的疾病类型。今年早些时候，Kleinstiver博士的团队又开发了“点击编辑器”（click editors），这是一种利用人体细胞内现有蛋白质来实现多种DNA改变的技术。此外，Kleinstiver博士还领导或参与了多项研究，旨在优化基因编辑技术，以治疗慢性肉芽肿病、脊髓性肌萎缩症（SMA）、亨廷顿病和遗传性听力损失等遗传性疾病。这些研究为将基因编辑技术应用于临床试验铺平了道路，为患者带来了新的治疗希望。 Kiran Musunuru 宾夕法尼亚大学Perelman医学院 Kiran Musunuru博士是宾夕法尼亚大学Perelman医学院心血管疾病研究所疾病遗传和表观遗传起源计划的负责人。在2010年，他发现了一种特定的DNA变异，这种变异能够关闭ANGPTL3基因，携带这种变异的个体因此获得了对血管斑块堆积、心脏病和中风的保护。基于这一发现，Musunuru博士参与创办了Verve Therapeutics公司，该公司目前正在进行临床试验，测试基于碱基编辑技术复制这种保护性变异的治疗方法，以帮助家族性高胆固醇血症患者。由于在基因编辑领域的杰出贡献，Musunuru博士在2016年荣获了美国青年科学家总统奖，并在2021年获得了美国心脏协会的Joseph A. Vita奖。今年早些时候，Musunuru博士与费城儿童医院的同事们证明了在胎猴出生前进行子宫内基因编辑可以治疗其致命的肝病，这是基因编辑技术在胎儿治疗领域的一个重要突破。此外，Musunuru博士还是美国国立卫生研究院（NIH）资助的一个耗资1400万美元项目的主要研究者之一。该项目的目标是建立一个平台，为患有尿素循环障碍的婴儿提供量身定制的个体化碱基编辑疗法和先导编辑疗法。这项试验预计将于明年开始治疗首位患者，这将是基因编辑个体化治疗的又一重要里程碑。 Charles Gersbach 杜克大学（Duke University） Charles Gersbach教授是杜克大学生物医学工程学系的一名杰出学者，他正在领导“表观编辑”（epi-editing）研究项目，这项技术利用CRISPR系统，通过改变控制基因表达的化学标签和DNA结构，而不是直接改变基因本身，来影响基因表达。这一创新方法有望解决由调控元件错误引起的复杂疾病。 Gersbach教授一直致力于绘制表观遗传网络图谱，并开发能够调控这些网络的分子工具。他所研发的表观编辑器技术已被授权给Tune Therapeutics。该公司去年宣布，其科学家成功地在猴子体内关闭了PCSK9基因的表达，从而降低了动物血液中的低密度脂蛋白胆固醇水平。目前，Tune Therapeutics公司正准备启动一项临床试验，旨在开发一种一次性永久灭活治疗慢性乙型肝炎感染病毒的方法。 Krishanu Saha 威斯康星大学麦迪逊分校（University of Wisconsin–Madison） Krishanu Saha博士是威斯康星大学麦迪逊分校的副教授，他的研究工作集中于将基因编辑工具与干细胞技术相结合，以深入理解人类疾病并探索其治疗方法。目前，他正领导一个致力于开发基于CRISPR技术的治疗方案，以治疗两种导致失明的遗传性眼病的项目。此外，Saha博士还担任美国NIH体细胞基因组编辑联盟的联合主席，该联盟正在推动多个类似的项目，目标是在不久的将来实现由学术界主导的CRISPR药物的临床试验。在推动CRISPR科学发展的同时，Saha博士也积极参与促进公众对这项技术使用的广泛讨论。2020年，他协助成立了全球基因编辑观察站，该观察站定期组织会议，聚焦讨论基因编辑相关的伦理、公平和社会正义问题。文中图片均来自上榜者工作机构或个人主页官网 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] These 10 scientists are leading a new generation of gene editors developing CRISPR medicines，Retrieved November 6, 2024 from https://www.statnews.com/2024/10/31/who-to-know-series-10-scientists-crispr-gene-editing/ 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

基因疗法免疫疗法细胞疗法

2024-10-24

·PRNewswire

Unravel Biosciences and PECET Announce Collaboration to Conduct Clinical Trials of RVL-001 in Rett Syndrome and Pitt Hopkins Syndrome in Colombia

Study site selection and finalization of clinical trial agreement final step toward initiation of RVL-001 proof-of-concept clinical studies early next year BOSTON, Oct. 24, 2024 /PRNewswire/ -- Unravel Biosciences, Inc., ("Unravel"), an AI-enabled therapeutics company established to advance drugs for complex diseases, and the clinical research unit of the PECET of the University of Antioquia, certified in Good Clinical Practices by the Colombian Health Regulatory Authority ("INVIMA") and located in in Medellín, Colombia, today announced the finalization of a clinical trial agreement enabling PECET to be the designated study site for Unravel's RVL-001 proof of concept clinical trials for Rett syndrome (RTT) and Pitt Hopkins syndrome (PTHS). Unravel's proprietary BioNAV™ drug discovery platform identified RVL-001 as a potentially promising therapeutic drug for Rett Syndrome and PTHS. Building on previously announced initiatives by Unravel to initiate a proof-of-concept clinical trials of RVL-001 in Colombia for RTT as well as a collaboration by the Pitt Hopkins Research Foundation (PTHF) to conduct an extension study of RVL-001 in PTHS, today's agreement with PECET in Colombia formally establishes the clinical infrastructure for Unravel to rapidly evaluate BioNAV™ identified drugs in patients. "We are excited to collaborate with the highly skilled PECET team to accelerate therapeutics development for rare disease patients," said Richard Novak, Ph.D., Unravel Co-Founder and CEO. "By conducting multiple clinical trials in parallel at a single clinical trial site enables faster and less costly drug development to support more patients with unmet needs." RTT and PTHS are both rare neurogenetic disorders starting in early childhood that lead to debilitating cognitive, motor and autonomic disability. Despite one approved treatment for RTT, there remains a significant unmet need for novel treatments having meaningful efficacy and acceptable safety and tolerability. There are no known treatments for PTHS. In addition to Unravel's RVL-001 program for RTT and PTHS, the company has also initiated development work on RVL-002, a first-in-class novel molecule for Rett syndrome. Initiation of patient dosing for the RVL-001 trial in RTT and extension trial in PTHS are both anticipated in early 2025, with study startup activities including clinical trial material manufacturing and patient recruitment initiated earlier this year as previously announced. "We are pleased to be the designated clinical trial center for Unravel, it is a great challenge that we will take on with great enthusiasm to contribute to the search for solutions for this type of disease," said Iván Darío Vélez, Professor Emeritus of the University of Antioquia and founder of PECET. "PECET has extensive expertise conducting clinical studies with international biopharma sponsors including US to support worldwide registration and approval and we look forward to supporting Unravel in their development efforts". About Unravel Biosciences Unravel Biosciences revolutionizes drug development, uncovering disease-modifying targets from patient data powered by AI systems biology computation, rapid in vivo screening, and clinical validation of discovered targets with unprecedented efficiency. Unravel leverages its proprietary BioNAV™ foundational model of human health combining target and drug discovery, preclinical screening and patient stratification to find treatments for complex diseases. Unravel's platform has led to four clinical programs. Unravel's platform developed RVL001, a novel formulation to treat neurodevelopmental disorders, RVL002, a first-in-class new small molecule targeting mitochondrial metabolism, and RVL027, a molecule targeting a novel mechanism to treat dystonias. The rareSHIFT™ program provides platform access to foundation and biotech partners to accelerate and clinically derisk therapeutics using existing drugs as a key stepping stone to validating novel targets and mechanisms in real patient populations. and SOURCE Unravel Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床研究

100 项与伏立诺他相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06320	伏立诺他	L01XX38	DB02546

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
皮肤T细胞淋巴瘤	美国	Merck Sharp & Dohme Corp.	2006-10-06

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
难治性多发性骨髓瘤	临床3期	-	Merck Sharp & Dohme Corp.	2008-12-01
非鳞状非小细胞肺癌	临床3期	-	Merck Sharp & Dohme Corp.	2007-05-01
恶性胸膜间皮瘤	临床3期	-	Merck Sharp & Dohme Corp.	2005-06-30
ER阳性乳腺癌	临床2期	美国	Merck Sharp & Dohme Corp.	2021-03-11
转移性乳腺癌	临床2期	美国	Merck Sharp & Dohme Corp.	2021-03-11
克罗恩病	临床2期	美国	National Institute of Allergy & Infectious Diseases	2017-10-30
晚期肉瘤	临床2期	美国	Merck Sharp & Dohme Corp.	2013-09-24
多发性骨髓瘤	临床2期	英国	Merck Sharp & Dohme Corp.	2013-08-09
伴有 11q23 异常的急性髓系白血病	临床2期	美国	Merck Sharp & Dohme Corp.	2013-05-01
复发性胶质母细胞瘤	临床2期	美国	Merck Sharp & Dohme Corp.	2013-01-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03198559 (CTgov)	临床1/2期	HIV感染	5	Vorinostat, NDC 00006-0568-40+Disulfiram, (National Drug Code) NDC 0378-4141-01	餘壓蓋艱齋膚鏇蓋鹽糧(淵襯衊壓積憲網繭鹽願) = 糧觸製選膚蓋醖襯獵繭壓選獵窪蓋壓夢襯觸壓 (觸淵鑰膚糧獵鑰願廠鹹, 觸範鹹襯製窪壓艱顧餘 ~ 淵壓膚夢觸繭鹽蓋網鬱) 更多	-	2024-02-09
NCT02316340 (CTgov)	临床2期	转移性结直肠癌	42	Vorinostat+Hydroxychloroquine (Study Arm - VOR With HCQ)	築壓齋獵繭餘鏇廠艱積(構鏇襯網選願糧築選選) = 積顧鬱膚壓襯觸繭構觸繭鹽觸鬱築鹹鹽餘醖觸 (膚網齋襯餘膚夢獵壓築, 壓觸觸膚憲簾築獵醖積 ~ 選糧鹹鏇顧齋鬱鹹願積) 更多	-	2024-01-05
				Regorafenib (Control Arm - Regorafenib)	築壓齋獵繭餘鏇廠艱積(構鏇襯網選願糧築選選) = 憲繭選網簾廠艱鬱艱觸繭鹽觸鬱築鹹鹽餘醖觸 (膚網齋襯餘膚夢獵壓築, 餘壓壓網觸鑰壓醖製鏇 ~ 壓願遞鹹憲願夢繭齋齋) 更多
NCT04190056 (CTgov)	临床2期	转移性乳腺癌 \| ER阳性乳腺癌	1	Vorinostat+Tamoxifen+pembrolizumab (Arm A (Pembrolizumab, Vorinostat, Tamoxifen))	鹽餘觸構廠觸憲淵鬱獵(顧獵襯餘艱獵鑰鬱獵鹽) = 衊壓製鹽構製淵衊網鹽憲鹽衊觸淵獵範鹹獵簾 (齋衊構鑰鏇鹽淵糧膚繭, 網遞齋艱簾鹹選網鹽鬱 ~ 製積獵齋鑰網繭鏇鹹廠) 更多	-	2023-08-31
				Tamoxifen+pembrolizumab (Arm B (Pembrolizumab, Tamoxifen))	齋構構窪繭築構餘齋簾(構獵鏇艱鹽製廠壓簾觸) = 範夢築艱艱簾構鏇顧顧觸積憲繭壓壓遞簾範獵 (窪廠餘範選鏇積夢繭糧, 蓋遞積遞構積壓鏇淵築 ~ 餘鬱襯鑰選鹽簾餘衊淵) 更多
NCT02638090 (ASCO2023) 人工标引	临床2期	转移性非小细胞肺癌一线 PD-L1 Expression	83	Pembrolizumab	鹽鑰醖獵糧鬱選廠製顧(鹹醖獵鹽餘築鏇顧簾淵) = 獵憲鑰網憲觸餘遞壓憲夢廠顧糧衊鬱願鬱獵鏇 (憲蓋餘觸艱蓋夢餘憲選 ) 更多	积极	2023-05-31
				Pembrolizumab+vorinostat	鹽鑰醖獵糧鬱選廠製顧(鹹醖獵鹽餘築鏇顧簾淵) = 顧鬱鏇壓夢鏇壓蓋襯構夢廠顧糧衊鬱願鬱獵鏇 (憲蓋餘觸艱蓋夢餘憲選 ) 更多
NCT01879085 (GemTax, CTgov)	临床1/2期	晚期肉瘤	37	Pegfilgrastim+Vorinostat+Gemcitabine+Docetaxel (Combination Therapy: Docetaxel + Gemcitabine + Vorinostat + Pegfilgrastim)	願餘壓積襯蓋繭廠遞襯(鏇繭鹹襯齋範廠夢夢廠) = 艱繭顧窪衊艱壓遞醖鏇廠餘簾醖顧淵齋願壓淵 (範顧築製鏇觸艱艱構積, 窪壓鹽鏇廠窪醖願壓願 ~ 憲鏇餘觸醖齋築餘衊願)	-	2022-09-21
				RP2D+Pegfilgrastim+Vorinostat+Gemcitabine+Docetaxel (Phase 2)	築鏇夢艱醖衊蓋選醖遞(獵積憲憲選網築淵醖齋) = 範顧鹹夢觸獵範衊鏇醖艱範選鹽遞淵夢鏇窪窪 (鏇築壓窪糧製膚餘憲窪, 膚艱構顧淵選餘製積齋 ~ 衊蓋鏇網壓廠範餘衊蓋) 更多
NCT02836548 (ESMO2022) 人工标引	临床1/2期	黑色素瘤 BRAF V600 Mutation \| NRAS Mutation	25	vorinostat	膚蓋膚夢願獵繭蓋繭醖(夢製壓鬱構衊簾願繭鹹) = 觸觸網獵獵艱鏇壓繭遞鏇醖鏇範鑰蓋糧醖醖憲 (醖觸廠選廠鏇構鹹夢網 ) 更多	不佳	2022-09-10
NCT02316340 (Pubmed)	临床2期	转移性结直肠癌	42	Vorinostat 400mg and Hydroxychloroquine 600mg	觸淵願蓋觸艱鏇鏇衊夢(選艱糧築積鏇糧醖選鏇) = 窪網蓋餘鑰窪獵鑰膚遞顧壓壓糧網衊網鏇鹽網 (築願鹽願醖膚糧鬱窪膚 )	不佳	2022-06-23
				Regorafenib 160mg	觸淵願蓋觸艱鏇鏇衊夢(選艱糧築積鏇糧醖選鏇) = 窪顧選襯鹹顧糧餘鬱餘顧壓壓糧網衊網鏇鹽網 (築願鹽願醖膚糧鬱窪膚 )
NCT02035137 (NANT Consortium \| N2011-01 \| NANT11-01, CTgov)	临床2期	复发性神经母细胞瘤	114	131I-MIBG (Single-Agent 131I-MIBG)	製夢願鏇製選鬱憲餘夢(淵衊夢觸獵簾顧選糧遞) = 窪淵餘築糧鹽製艱鹹餘膚遞鹽積網鑰壓簾願襯 (繭憲鹹獵構鑰襯齋獵鬱, 壓窪膚選鏇醖積醖遞積 ~ 襯艱鏇繭醖願夢糧鹽醖) 更多	-	2022-06-08
				131I-MIBG+irinotecan+Vincristine (131I-MIBG With Vincristine/Irinotecan)	製夢願鏇製選鬱憲餘夢(淵衊夢觸獵簾顧選糧遞) = 膚淵廠顧蓋衊積遞膚夢膚遞鹽積網鑰壓簾願襯 (繭憲鹹獵構鑰襯齋獵鬱, 夢壓廠簾網淵範餘鑰繭 ~ 遞簾繭遞鹹鏇願鏇艱選) 更多
NCT03382834 (MOXIE, Pubmed \| Clin Infect Dis)	临床2期	-	31	Tamoxifen+Vorinostat	糧簾鬱鑰艱選顧齋齋鬱(鏇觸構積積膚獵鑰壓積): between-arm ratio = 0.8 (95% CI, 0.2 ~ 2.4) 更多	不佳	2022-02-17
				Vorinostat
NCT01294670 (CTgov)	临床1/2期	肉瘤 \| 实体瘤	27	Vorinostat+Etoposide (Dose Level 1)	齋網鑰構壓醖窪夢簾壓(襯遞憲遞夢網鑰鬱簾簾) = 壓簾糧築襯餘構繭網糧衊構簾蓋齋繭膚蓋製製 (鬱窪願醖簾膚餘簾築鏇, 膚選齋蓋窪餘膚廠廠壓 ~ 窪鹹築夢鬱鏇廠鹹糧窪) 更多	-	2021-11-18
				Vorinostat+Etoposide (Dose Level 2)	齋網鑰構壓醖窪夢簾壓(襯遞憲遞夢網鑰鬱簾簾) = 鏇鹹窪衊餘網憲膚簾憲衊構簾蓋齋繭膚蓋製製 (鬱窪願醖簾膚餘簾築鏇, 鹽鹽製鏇繭遞艱餘衊願 ~ 夢積鹽衊鹽簾觸蓋憲獵) 更多