更新于：2024-11-01

Polyglucosan Body Disease, Adult Form

成人多聚糖体病

更新于：2024-11-01

基本信息

别名

APBD、APBN、Adult Polyglucosan Body Disease

+ [10]

简介

A glycogen storage disease of adults with characteristics of progressive upper and lower motor neuron dysfunction, progressive neurogenic bladder and cognitive difficulties that can lead to dementia. The prevalence is unknown. More than 50 cases have been described to date in Ashkenazi (in most cases) and non-Ashkenazi Jewish individuals. Presents after the age of 40, with urinary incontinence (indicative of neurogenic bladder) often being the first manifestation. Caused by a mutation in the GBE1 gene, encoding the glucan (1, 4-alpha-) branching enzyme 1 (GBE).

关联

项与成人多聚糖体病相关的药物

Triheptanoin

三庚酸甘油酯

靶点-

作用机制

脂肪酸替代品 [+1]

在研机构

Ultragenyx Pharmaceutical, Inc.

原研机构

Baylor Research Institute

在研适应症

脂肪酸氧化代谢病 [+3]

非在研适应症

肌萎缩侧索硬化 [+19]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2020-06-30

TGTX-112

靶点-

作用机制

基因转移

在研机构

The University of Texas Southwestern Medical Center [+1]

原研机构

The University of Texas Southwestern Medical Center

在研适应症

成人多聚糖体病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

GHF-201

靶点

LAMP-1

作用机制

LAMP-1抑制剂

在研机构

Golden Heart Flower Ltd.

原研机构

Golden Heart Flower Ltd.

在研适应症

成人多聚糖体病 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与成人多聚糖体病相关的临床试验

NCT02683512 / RecruitingN/AIIT

GBE Deficiency (GSD IV and APBD) Natural History Study

Collection and review of clinical information related to glycogen branching enzyme (GBE) deficiency, diagnosed as Glycogen Storage Disease Type IV (GSD IV) or Adult Polyglucosan Body Disease (APBD generated during clinic visits.

开始日期2015-12-01

申办/合作机构

Duke University

NCT00947960 / Completed临床2期IIT

A Treatment Trial of Triheptanoin in Patients With Adult Polyglucosan Body Disease - A Randomized Controlled Study

The purpose of the study is to determine if triheptanoin is an effective treatment for the symptoms of Adult Polyglucosan Body Disease.

开始日期2009-06-01

申办/合作机构

Baylor Research Institute

[+1]

100 项与成人多聚糖体病相关的临床结果

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100 项与成人多聚糖体病相关的转化医学

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0 项与成人多聚糖体病相关的专利（医药）

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169

项与成人多聚糖体病相关的文献（医药）

2024-09-01·Journal of the Neurological Sciences

Development of the APBD-SQ, a novel patient-reported outcome for health-related quality of life in adult polyglucosan body disease

Article

作者: Li, Xiaochun ; Wilson, Genevieve E ; Goldman, Deberah S ; Saxe, Harriet ; Lau, Heather A ; Abreu, Nicolas J ; Goldberg, Judith D

Adult polyglucosan body disease (APBD) is a rare autosomal recessive glycogen storage disorder that leads to slowly progressive multi-organ dysfunction in adulthood. A novel disease-specific patient-reported outcome measure was created and administered to assess symptom burden and health-related quality of life (HR-QOL) in APBD. Thirty-six participants between 30 and 79 years of age (83% ≥60 years, 56% male) completed the anonymous questionnaire independently or with a caregiver proxy (75% self-report). Unemployment predicted an 18.3 (95% CI: 2.8, 33.8; p = 0.028) higher composite disease severity score and a 28.8 (95% CI: 8.2, 49.4; p = 0.010) higher composite HR-QOL score. Use of one or more assistive devices also predicted a 29.3 (95% CI: 8.3, 50.4; p = 0.011) higher composite disease severity score and a 41.8 (95% CI: 10.9, 72.8; p = 0.013) higher composite HR-QOL score. Proxy survey completion predicted a 19.4 (95% CI: 4.1, 34.7; p = 0.020) higher composite disease severity score compared to self-report. Older age at survey completion predicted a 27.4 higher composite HR-QOL score (95% CI: 2.5, 52.4; p = 0.039) for participants in their sixties compared to those between 30 and 59 years old. The development of the Adult Polyglucosan Body Disease questionnaire on Symptom burden and health-related Quality of life (APBD-SQ) marks an important stride forward in capturing the patient experience as a tool for disease monitoring and future research.

2024-09-01·Genes & Diseases

Clinical and genetic heterogeneity of adult polyglucosan body disease caused by GBE1 biallelic mutations in China

Article

作者: Gao, Yuan ; Hu, Yan ; Xu, Guorong ; Hong, Jingmei ; Shi, Yan ; He, Jin ; Zhou, Linying ; Chen, Wanjin ; Lin, Xiang ; Chen, Yikun ; Gan, Shirui

2024-06-01·Acta Neuropathologica

Myofiber-type-dependent ‘boulder’ or ‘multitudinous pebble’ formations across distinct amylopectinoses

Article

作者: Shelton, John M ; Dear, Mathew ; Nitschke, Silvia ; Nitschke, Felix ; Fuseya, Yasuhiro ; Iwai, Kazuhiro ; Minassian, Berge A ; Covington, Lindsay ; Evers, Bret M ; Lynn, Tori ; Wu, Jun ; Verma, Mayank ; Chen, Baozhi ; Mitra, Sharmistha

At least five enzymes including three E3 ubiquitin ligases are dedicated to glycogen's spherical structure. Absence of any reverts glycogen to a structure resembling amylopectin of the plant kingdom. This amylopectinosis (polyglucosan body formation) causes fatal neurological diseases including adult polyglucosan body disease (APBD) due to glycogen branching enzyme deficiency, Lafora disease (LD) due to deficiencies of the laforin glycogen phosphatase or the malin E3 ubiquitin ligase and type 1 polyglucosan body myopathy (PGBM1) due to RBCK1 E3 ubiquitin ligase deficiency. Little is known about these enzymes' functions in glycogen structuring. Toward understanding these functions, we undertake a comparative murine study of the amylopectinoses of APBD, LD and PGBM1. We discover that in skeletal muscle, polyglucosan bodies form as two main types, small and multitudinous ('pebbles') or giant and single ('boulders'), and that this is primarily determined by the myofiber types in which they form, 'pebbles' in glycolytic and 'boulders' in oxidative fibers. This pattern recapitulates what is known in the brain in LD, innumerable dust-like in astrocytes and single giant sized in neurons. We also show that oxidative myofibers are relatively protected against amylopectinosis, in part through highly increased glycogen branching enzyme expression. We present evidence of polyglucosan body size-dependent cell necrosis. We show that sex influences amylopectinosis in genotype, brain region and myofiber-type-specific fashion. RBCK1 is a component of the linear ubiquitin chain assembly complex (LUBAC), the only known cellular machinery for head-to-tail linear ubiquitination critical to numerous cellular pathways. We show that the amylopectinosis of RBCK1 deficiency is not due to loss of linear ubiquitination, and that another function of RBCK1 or LUBAC must exist and operate in the shaping of glycogen. This work opens multiple new avenues toward understanding the structural determinants of the mammalian carbohydrate reservoir critical to neurologic and neuromuscular function and disease.

项与成人多聚糖体病相关的新闻（医药）

2024-02-19

·GlobeNewswire-Health Care

Taysha Gene Therapies Provides Update on Deprioritized Pipeline Programs

Feb. 15, 2024 -- Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (“Taysha” or “the Company”), a clinical-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS), today provided an update on its deprioritized pipeline programs as part of an ongoing effort to help support their further potential development. Taysha has been working to find ways to advance its deprioritized programs. On November 13, 2023, Taysha terminated its existing loan and security agreement and entered into a new loan and security agreement that provides consent to allow the Company to transfer intellectual property (IP) for several deprioritized programs to third parties in a more efficient manner. The Company’s new loan and security agreement also extended its cash runway into 2026. TSHA-120: The Company initiated the transfer of the United States Food and Drug Administration Investigational New Drug (IND) application and investigational clinical trial material for TSHA-120 in giant axonal neuropathy (GAN) to clinical trial collaborator National Institute of Neurological Disorders and Stroke (NINDS), creating an opportunity for continued clinical evaluation of TSHA-120 in GAN. Additionally, the Company entered discussions with the originating advocacy organization regarding TSHA-120 in an effort to transfer rights back to the advocacy organization to move the program forward. TSHA-101: The Company transferred rights back to Queen’s University (Queen’s) for TSHA-101 in GM2 gangliosidosis, resulting in Queen’s regaining exclusive IP to the program. TSHA-104 and TSHA-112: The Company transferred rights back to the originating institution for select programs, including TSHA-104 in SURF1-associated Leigh syndrome and TSHA-112 in APBD. TSHA-118: The Company provided investigational clinical trial material for TSHA-118 in CLN1 to support an individual-patient investigator-initiated IND request from RUSH University Medical Center for the treatment of a patient with CLN1 disease. “Today’s announcement demonstrates meaningful progress to advance important development work for several deprioritized programs. Creating options for these programs has been a focus since the Company completed a management change in December 2022, and the new loan and security agreement afforded the flexibility to implement certain opportunities,” said Sean P. Nolan, Chairman and Chief Executive Officer of Taysha. “As we continue to focus on advancing our lead TSHA-102 program for the treatment of Rett syndrome, we are pleased that we can ensure these programs are provided to the right advocates, clinicians and scientific experts who can potentially move these programs forward for the benefit of patients.” The Company continues to explore potential partnerships and opportunities for its other deprioritized programs to help support their further potential development. Taysha Gene Therapies (Nasdaq: TSHA) is a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. Its lead clinical program TSHA-102 is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the genetic root cause of the disease. With a singular focus on developing transformative medicines, Taysha aims to address severe unmet medical needs and dramatically improve the lives of patients and their caregivers. The Company’s management team has proven experience in gene therapy development and commercialization. Taysha leverages this experience, its manufacturing process and a clinically and commercially proven AAV9 capsid in an effort to rapidly translate treatments from bench to bedside. For more information, please visit www.tayshagtx.com. The content above comes from the network. if any infringement, please contact us to modify.

基因疗法引进/卖出

2022-08-30

·蒲公英Ouryao

多家药企新药临床试验获批

转自：蒲公英（ouryao.com) 整理：青于蓝一方面，创新药供给端有望诞生新的爆款产品，另一方面，新药研发是一项高风险、低成功率的技术创新，从实验室到新药上市是一个漫长而又复杂的过程，这个过程中的每一个步骤都有可能导致失败。据不完全统计，今年以来，多家药企宣布暂停或终止研发新药。部分药企新药研发或注册申请取得新进展近期，国内多家药企自主研发的新药临床试验获批，包括君实生物独立自主研发的单克隆抗体药JS009注射液等。业内人士表示，构建产品竞争力的核心是创新升级。随着创新药临床开发的规范化，临床资源相对紧张，新药开发成本上涨。复星医药：8月26日晚间，复星医药公告，控股子公司复宏汉霖的HLX60(重组抗GARP人源化单克隆抗体注射液)联合斯鲁利单抗注射液(汉斯状)用于晚期/转移性实体瘤治疗获准于澳大利亚进行临床试验。另外，复星医药控股子公司复宏汉霖自主研发的汉斯状联合顺铂和氟尿嘧啶(5-FU)一线治疗局部晚期/复发或转移性食管鳞状细胞癌(ESCC)的药品注册申请获国家药监局受理。康宁杰瑞：8月22日，国家药监局药品审评中心(CDE)信息显示，康宁杰瑞递交的两项临床试验申请获受理，分别为新型HER2双抗偶联药物(ADC)JSKN003的Ⅰ期临床研究、HER2双抗KN026与PD-L1/CTLA-4双抗KN046联合用药的Ⅲ期关键性临床研究。一方面，创新药供给端有望诞生新的爆款产品，众多创新药产品上市以后销售快速放量。另一方面，新药研发是一项高风险、低成功率的技术创新，从实验室到新药上市是一个漫长而又复杂的过程，这个过程中的每一个步骤都有可能导致失败。据不完全统计，今年以来，多家药企宣布暂停或终止研发新药。国外药企暂停/终止研发新药默沙东：今年8月，默沙东宣布其Keytruda联用Lenvima的Ⅲ期临床遭折戟。据悉，该项名为LEAP-002的临床试验，研究的优效性假设为帕博利珠单抗+乐伐替尼治疗HCC(即肝细胞癌)患者的疗效要优于乐伐替尼单药。不过结果却事与愿违，与单独接受乐伐替尼治疗相比，接受帕博利珠单抗+乐伐替尼治疗患者的总生存期等临床数据虽有改善趋势，但结果不具有统计学显著改善意义。3月15日，默沙东公司宣布，停止其PD-1产品Keytruda（中文商品名：可瑞达，简称K药）与PARP抑制剂Lynparza在联合治疗转移性去势抵抗性前列腺癌（mCRPC）的3期临床试验，原因在于，在进行中期数据分析后发现，与对照组醋酸阿比特龙或恩扎鲁胺相比，K药联合Lynparza并没有展现出生存获益。赛诺菲：日前，赛诺菲口服SERD amcenestrant联合用药的临床失败。这是继3月单药临床失败后的又一次失利。基于此，赛诺菲决定停止所有amcenestrant的临床试验。3月14日，赛诺菲发布消息称，其口服SERD药物amcenestrant在二期临床试验中，因没有达到主要终点，正式宣告失败。据了解，Amcenestrant一种优化的口服选择性雌激素受体降解剂，通过与乳腺癌细胞表面的雌激素受体结合，降低雌激素受体的稳定性，诱导它们被细胞正常的蛋白降解机制降解，从而降低雌激素受体水平，抑制癌细胞的生长。2月份，赛诺菲与再生元对抗炎药Dupixent治疗慢性自发性荨麻疹(CSU)3期项目进行了更新。根据预先指定的中期分析，评估Dupixent治疗奥玛利珠单抗(omalizumab)难治性CSU患者的一项3期试验(CUPIDSTUDYB)，因被判定无效而将停止。 MacroGenics：今年7月，MacroGenics核心在研产品B7-H3单抗伊布妥组单抗II期临床试验遭遇终止，此前天境生物与MacroGenics达成合作获得伊布妥组单抗在大中华区域的独家临床开发及销售权。罗氏：6月16日，罗氏和班纳老年痴呆症研究所联合宣布，crenezumab(克雷内治单抗)在阿尔茨海默症预防倡议(API)项目中的II期临床未达到主要研究终点。5月11日，罗氏公布的PD-L1+TIGIT联合一线治疗非小细胞肺癌三期临床SKYSCRAPER-01的中期数据研究结果显示，该研究没有达到其无进展生存期的共同主要终点。武田公司：今年7月消息，其产品线也发生了变化，其中一项为决定放弃与Turnstone Biologics公司联合开发的TAK-605管线。TAK-605是一种采用溶瘤病毒治疗癌症的方法，武田公司在获得药物许可后仅31个月就将该管线的权利归还给了Turnstone。武田列举了放弃TAK-605的“战略原因”，并计划继续使用Turnstone的技术平台发现新的候选药物。 Rigel Pharmaceuticals：6月，Rigel Pharmaceuticals宣布，Syk抑制剂fostamatinib(福他替尼)用于治疗温抗体型自身免疫性溶血性贫血的全球、多中心、随机、双盲、安慰剂对照III期FORWARD试验未达到主要终点。艾伯维：今年4月，艾伯维宣布终止与BioArctic的合作，停止帕金森病治疗药物α-突触核蛋白(aSyn)抗体ABBV-0805的后续临床开发。Nektar与百时美施贵宝：今年4月，Nektar与百时美施贵宝宣布终止与Opdivo联合使用的本加地尔的全球临床开发计划。国内药企暂停/终止研发三叶草生物：6月5日，三叶草生物也发布公告，公司表示在完成内部科学、财务和战略评估后，将资源优先配置给新冠肺炎相关的产品和某些早期项目，减少对非新冠相关的中期、后期项目和新基础设施的投入。在当前宏观经济环境中，公司将继续审慎评估开支，并探索可能的融资选择，以延长公司的现金生命周期。公司目前暂停了对SCB-313(T R A I L -三聚体肿瘤产品)、SCB -808和SCB-420(F c融合蛋白项目)的继续投入。沃森生物：6月14日，沃森生物发布了控股子公司上海泽润生物科技有限公司终止重组EV71疫苗研发的消息。据了解，重组EV71疫苗主要用于预防因EV71病毒感染导致的手足口病。上海泽润于2019年6月收到国家药品监督管理局批准的《临床试验通知书》。传奇生物：7月7日，传奇生物通知FDA，终止其针对CAR-T 新药LB1901的新药临床试验申请(IND)的1期临床试验。康辰药业：今年3月，北京康辰药业发布公告称，由于因需进一步完善申报资料，经审慎研究决定，康辰生物向国家药监局申请撤回特立帕肽注射液临床试验申请。据了解，特立帕肽注射液是康辰生物代理的进口注册产品，由Pfenex研发并获得FDA批准，系原研厂家礼来特立帕肽注射液的等效药品。 2021年12月，康辰生物和美国Alvogen,Inc.共同向国家药监局申报特立帕肽注射液临床试验申请并获得受理，特立帕肽是一种由34个氨基酸组成的重组人甲状旁腺激素（PTH）类似物（rhPTH[1-34]），能调节骨代谢、肾小管对钙和磷的重吸收，以及肠道钙吸收，适用于治疗绝经后妇女高骨折风险的骨质疏松症，以及糖皮质激素持续治疗诱发的高骨折风险的骨质疏松症。诺迪康药业：今年3月，西藏诺迪康药业发布公告称，公司与全资子公司成都诺迪康生物制药有限公司研发的重组人白细胞介素-1受体拮抗剂（rhIL-1Ra）滴眼液项目已完成IIa期临床实验研究，试验结果不及预期，经综合评估，公司决定暂停该新药的临床试验及后续研发。据介绍，重组人白细胞介素-1受体拮抗剂（rhIL-1Ra）滴眼液，拟用于轻中度角膜非感染性炎症的治疗，已完成IIa期临床实验研究。根据IIa期临床试验结果显示，rhIL-1Ra滴眼液安全性良好，但有效性需进一步探索。公司经审慎考量，基于对该滴眼液继续开发的风险性和未来临床价值的评估，以及后续开发投入和药物疗效的不确定性，决定暂停该药物的进一步研发。参考：中国证券报·中证网推荐阅读：蒲公英Ouryao视频号我们上线了蒲公英Ouryao视频号，每期3分钟，学习制药英语，用制药点燃你的语言星球。你的每一次“在看”，我都看得见！

抗体创新药免疫疗法合作疫苗