A Multicenter, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Velaglucerase Alfa in Chinese Subjects With Type 1 Gaucher Disease

The main purpose of this study is to observe the side effects of VPRIV in participants with type 1 Gaucher disease who are either treatment-naïve (newly diagnosed) or who are currently being treated with enzyme replacement therapy (ERT).
Participants will receive VPRIV intravenously during the treatment period (up to 51 weeks), followed by the end-of-treatment (EOT) visit after 2 weeks.

开始日期2023-01-03

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT03702361

/ Completed临床4期IIT

Rapid Intravenous Infusion of Velaglucerase Alfa (VPRIV) in Treatment-naive Patients With Type 1 Gaucher Disease: An Investigator-initiated Study

During the past two years, the investigator has performed succsefully an IIR wherein patients with GD, previously treated with velaglucerase alfa ERT were gradually switched to a 10 minutes (rapid) administration of the same ERT. The success was expressed as safety (no clinically meaningful AEs, no antibodies detected, home therapy), efficacy ("lack of deterioration") and patients' satisfaction. The latter was based not just on specific questionnaires and analog scales, but particularly by the patients' sharing the experience with other patients and consequently repeated requests by many to switch to a rapid administration of their ERT.
Therefore, the investigator is hereby proposing to investigate the safety and efficacy of a 10 minutes administration of velaglucerase alfa in a cohort of treatment-naive patients.
The current VPRIV label is restricted to a dosage of 60 units/kg body weight every other week (60 units/kg EOW) - this dose will be used throughout the study period. The enzyme will be provided by Shire, which will also provide a research grant for the conduction of the trial.

开始日期2018-09-04

申办/合作机构

Shaare Zedek Medical Center

NCT02574286

/ Completed临床4期

An Open-label, Multicenter, Single-arm, Phase 4 Study of the Effect of Treatment With Velaglucerase Alfa on Bone-related Pathology in Treatment-naïve Patients With Type 1 Gaucher Disease

The primary purpose of this study is to evaluate the effect of VPRIV therapy (60 units per kilogram [U/kg] every other week [EOW]) in treatment-naive participants with type 1 Gaucher disease on change from baseline in lumbar spine (LS) bone mineral density (BMD) Z-score as measured by dual energy x-ray absorptiometry (DXA) after 24 months of treatment.

开始日期2016-06-29

申办/合作机构

Shire Plc

100 项与维拉苷酶α 相关的临床结果

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100 项与维拉苷酶α 相关的专利（医药）

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项与维拉苷酶α 相关的文献（医药）

2026-04-01·Asian Journal of Pharmaceutical Sciences

Targeted delivery of glucocerebrosidase to lysosomes: The LYSOTAC (LYSOsome-TArgeting Chimera) technology

Article

作者: Park, Joo-Won ; Kang, Yang Jae ; Yoon, Sanghwa ; Lim, Hyomin ; Choi, Eun Nam ; Lee, Gee Eun ; Kwon, Yong Tae ; Kim, Minji ; Jung, Eui Jung ; Mun, Su Ran ; Park, Woo-Jae ; Kim, Hee-Yeon

Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders caused by misfolding of lysosomal proteins and their degradation via endoplasmic reticulum-associated degradation (ERAD). Deficiency in LSD-associated enzymes leads to the accumulation of toxic materials within the lysosome. In macroautophagy (hereafter autophagy), autophagic receptors as represented by p62/SQSTM1/Sequestosome-1 collect and deliver their cargoes to the lysosome. Here, we developed the LYSOTAC (LYSOsome-TArgeting Chimera) technology, which enables lysosomal targeting of LSD-associated enzymes while preserving their enzymatic activities. LYSOTAC employs a bifunctional chimera that simultaneously binds an LSD-associated enzyme via the enzyme-binding ligand (EBL) and p62 via the autophagy-targeting ligand (ATL). Upon binding, p62 undergoes self-polymerization to form cargo-p62 complexes, which are sequestered into autophagosomes and delivered to lysosomes, where the enzymes exhibit maximal activity. Here, LYSOTAC compounds targeting β-glucocerebrosidase (GCase) were designed to restore GCase activity in lysosomes and promote glucosylceramide degradation in Gaucher disease fibroblasts. We suggest that LYSOTAC provides a potential therapeutic strategy for LSDs.

2026-04-01·JOURNAL OF NEUROCHEMISTRY

Antisense Oligonucleotides in Parkinson's Disease: Challenges, Opportunities, and the Promise of Low‐Intensity Focused Ultrasound for Brain Delivery

Review

作者: Blesa, Javier ; Obika, Shunsuke

ABSTRACT:

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuronal loss in the basal ganglia, for which no disease modifying therapy is currently available. Antisense oligonucleotides (ASOs) have emerged as promising therapeutic candidates, and numbers of preclinical studies with PD models have demonstrated their potential to inhibit α‐synuclein aggregation. However, a major obstacle to clinical application of ASOs in neurodegenerative diseases is their limited permeability across the blood–brain barrier. Consequently, currently approved ASOs for neurological disorders are administered intrathecally, which makes it difficult to achieve efficient drug delivery to deep brain structures such as the basal ganglia. Focused ultrasound (FUS)‐induced blood–brain barrier opening has attracted interest as a noninvasive strategy to enhance central nervous system drug delivery. Clinical studies have demonstrated that FUS‐mediated blood–brain barrier opening can be performed safely in patients with PD and effective delivery of therapeutic agents, such as glucocerebrosidase. Yet, evidence for effective delivery of ASOs to the brain via FUS‐induced blood–brain barrier opening is still lacking. This review summarizes current studies of ASOs in PD, together with recent advances in FUS‐mediated blood–brain barrier opening. We highlight remaining biological and translational limitations and outline future perspectives for optimizing ASOs delivery with FUS‐mediated blood–brain barrier opening to accelerate disease‐modifying therapy for PD.image

2026-02-27·Cureus Journal of Medical Science

Comparative Evaluation of Glucose Levels in Gingival Crevicular Blood and Peripheral Blood Using Two Different Glucometers in Patients Suffering From Periodontal Disease

Article

作者: Mahanta, Putul ; Nath, Barsha ; Sharma, Maitreyee ; Medhi, Rakesh K ; Talukdar, Alpana

INTRODUCTION:

Given dentists' increasing role in healthcare, dental clinics may be essential sites for diabetes screening. Gingival bleeding is a hallmark of periodontal inflammation. Gingival crevicular blood (GCB) collection with a portable glucometer for glucose measurement is a safer, more convenient, patient-friendly, and time-saving option. The primary objective of the current investigation was to compare random blood glucose levels with those in gingival crevicular and peripheral blood, as determined using two different glucometers. The study's secondary goal was to assess the feasibility and inter-glucometer agreement of estimating blood sugar from gingival crevicular blood using a glucometer as a chairside diabetes screening tool.

METHODS:

The present study included 85 patients with bleeding during probing in the maxillary anterior region. The GCB sample was collected from an appropriate site of the maxillary anterior teeth. Peripheral blood (PB) samples were collected from the patients' right index fingers to determine PB glucose levels. Blood glucose levels were measured using glucometers from two different brands: Dr. Morepen (A) and Contour Plus (B). Venous blood samples were used to determine random blood sugar (RBS) level using laboratory methods. The data were divided into five groups: GCB A: GCB evaluated by glucometer A; GCB B: GCB evaluated by glucometer B; PB A: PB evaluated by glucometer A; PB B: PB evaluated by glucometer B; and RBS: random blood sugar. Bland-Altman analysis was used for intergroup comparisons. Concordance correlation analysis across groups was performed to assess the concordance between two variables. Intraclass correlation was used to assess absolute agreement among the different methods of blood glucose measurement. A p-value of less than 0.05 was considered significant.

RESULTS:

The present study comprised 85 participants. The participants' ages ranged from 15 to 70 years. The majority, 53 (62.4%) of the participants, were male. Almost 94% (n=80) of the participants were normoglycemic. The mean glucose level was highest in the PB group (102.68 mg/dL) and lowest in the GCB B group (99.58 mg/dL). There was no significant systematic bias between GCB A with RBS (mean difference = -0.23, 95% CI: -2.22 to 1.77) and PB B (mean difference = 0.09, 95% CI: -1.84 to 2.02), whereas PB A exhibited systematic overestimation. Furthermore, RBS (mean difference=0.88, 95% CI: -0.91 to 2.66), PB B (mean difference=1.20, 95% CI: -0.60 to 3.00), and GCB A (mean difference=1.11, 95% CI: -0.42 to 2.63) are less biased than GCB B. Both GCB A and GCB B showed significant concordance with RBS, PB A, and PB B (correlation coefficients >0.95, p-values <0.001). The two glucometers under study showed almost perfect absolute agreement in estimating blood sugar levels from gingival crevicular blood (ICC single-measure value > 0.9) and peripheral blood (single-measure value > 0.9).

CONCLUSION:

GCB oozing from periodontal pockets during routine examination may be used for glucose estimation as precisely as that from peripheral and venous blood. There is no statistically significant difference in glucose estimation results obtained with the two glucometers used in the study. GCB can serve as a source for noninvasive glucose monitoring in a dental setting.

项与维拉苷酶α 相关的新闻（医药）

2026-05-19

·创药网

溶酶体功能障碍：分子机制与疾病关联

溶酶体是维持细胞内稳态的关键细胞器，传统上被认为主要负责大分子降解与再循环。然而，近年来的研究表明，溶酶体不仅是细胞内的终末降解区室，还作为信号整合与代谢调控的核心枢纽参与多种生理过程，包括自噬、免疫反应、能量代谢以及细胞死亡调控。溶酶体功能障碍已被证实与神经退行性疾病、心血管疾病、肿瘤及免疫失调密切相关。与此同时，以溶酶体离子通道如TRPML1为代表的关键调控分子逐渐成为药物研发的重要靶标，靶向溶酶体降解途径的新型技术，如LYTAC、AUTAC和TransTAC等，进一步拓展了蛋白质降解疗法的应用范围。本文综述了溶酶体的结构与功能、其在多种疾病中的致病作用，以期为科研人员提供参考。溶酶体的结构与功能溶酶体（Lysosome）长期被视为细胞内的终末降解室，其主要功能在于分解来自内吞、吞噬及自噬途径的生物大分子。然而，现代细胞生物学研究表明，溶酶体不仅是降解平台，同时也是整合代谢、应激与信号转导的核心细胞器，在维持细胞稳态中发挥枢纽作用。溶酶体起源于内质网和高尔基体途径。新合成的水解酶在粗面内质网合成后，经高尔基体加工并通过甘露糖-6-磷酸（Mannose-6-phosphate，M6P）标记被分选进入运输囊泡，在Rab GTP酶和AP3复合物等调控下与晚期内体融合，最终形成成熟溶酶体。成熟溶酶体由单层脂质膜包裹，内部富含多种酸性水解酶，其腔内pH维持在约4.5～5.0，这一酸性环境依赖液泡型质子泵V-ATPase持续将H⁺泵入腔内，同时由氯通道7/成骨不全相关跨膜蛋白1（ClC-7/Ostm1）复合物介导Cl⁻转运以维持电荷平衡。溶酶体膜上分布着多种离子通道与转运体，其中以瞬时受体电位黏脂蛋白1（TRPML1）、双孔通道（Two-pore channels，TPCs）以及ClC-7最具代表性。这些蛋白通过调节Na⁺、Ca²⁺与Cl⁻等离子的跨膜转运维持溶酶体的电化学稳态，并参与膜融合、囊泡运输及溶酶体外排等关键过程。这些离子通道中，TRPML1被认为是溶酶体最重要的Ca²⁺释放通道之一。TRPML1主要定位于晚期内体和溶酶体膜，能够介导Ca²⁺、Zn²⁺和Fe²⁺从溶酶体腔内向细胞质释放，从而触发溶酶体与自噬体的融合以及溶酶体外排。此外，该通道对氧化应激高度敏感，在活性氧水平升高时可被激活，使其成为细胞应对氧化损伤的重要调节节点。除离子通道外，溶酶体膜还含有多种结构与运输相关蛋白。溶酶体相关膜蛋白1/2（Lysosome-associated membrane protein 1/2，LAMP1/2）是维持溶酶体膜稳定性的主要结构蛋白，其中LAMP2A作为伴侣介导自噬（Chaperone-mediated autophagy，CMA）的受体，能够识别含KFERQ基序的底物蛋白，并在HSPA8等分子伴侣协助下介导其跨膜转运进入溶酶体腔内降解。可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（Soluble N-ethylmaleimide-sensitive factor attachment protein receptor，SNARE）复合物与Rab GTP酶则协同调控囊泡的靶向、系链及膜融合过程，是溶酶体与内体及自噬体融合的关键执行系统。除了降解与膜运输功能，溶酶体还是重要的代谢信号整合平台。哺乳动物雷帕霉素靶蛋白1（mTORC1）复合物定位于溶酶体膜表面，其活性受氨基酸水平通过Rag GTP酶及Rag调节蛋白复合物调控。当营养充足时，mTORC1被招募至溶酶体并保持活化，从而抑制自噬；而在营养缺乏时，mTORC1从溶酶体解离并失活，诱导自噬启动，使溶酶体成为连接细胞营养状态与分解代谢反应的关键节点。溶酶体的生物发生及功能重编程主要受转录因子EB（Transcription Factor EB，TFEB）调控。TFEB能够识别并激活协同溶酶体表达与调节基因网络，驱动溶酶体水解酶及膜蛋白的表达。在mTORC1失活或溶酶体受损时，TFEB去磷酸化并转位入核，从而增强自噬和溶酶体生成。此外，溶酶体Ca²⁺释放可通过激活钙调神经磷酸酶（Calcineurin）进一步促进TFEB去磷酸化。近期研究还表明，TFEB的活化受到泛素化调控，例如E3连接酶SMAD特异性E3泛素连接酶1（SMAD ubiquitin regulatory factor 1，SMURF1）通过调节蛋白磷酸酶3催化亚基β（Protein phosphatase 3 catalytic subunit beta，PPP3CB）的稳定性促进TFEB核转位，从而维持溶酶体稳态（图1）。溶酶体中的各种成分，比如酶类、膜结合蛋白/复合物、转运蛋白和离子通道等，都是治疗溶酶体功能障碍的理想靶标。图1：溶酶体中的分子靶标及可作为治疗策略的机制溶酶体功能障碍与疾病发生在自噬过程、营养物质感知、物质分泌、伤口愈合、钙离子信号传导、神经元退化以及基因表达等方面，溶酶体发挥着至关重要的作用。由于降解或转运功能出现缺陷而导致的溶酶体稳态失衡，会引发多种疾病，最为直接的为溶酶体贮积症（Lysosomal storage diseases）。同时，溶酶体功能障碍也会导致其他细胞器的异常运作，进而成为阿尔茨海默病和帕金森病等神经元退行性疾病的诱因。此外，溶酶体介导的蛋白质降解能力下降也是衰老过程中的一个重要特征。 01 溶酶体贮积症溶酶体功能障碍可直接引发一类经典的遗传性疾病——溶酶体贮积症。该病通常由单一溶酶体酶的缺失或功能异常所致，特定底物在溶酶体内累积，从而引发细胞损伤及系统性病变。典型疾病包括由葡萄糖脑苷脂酶（Glucocerebrosidase，GBA）缺陷引起的Gaucher病，表现为肝脾肿大、骨病及部分神经系统损伤；由α-半乳糖苷酶（α-galactosidase A）缺陷导致的Fabry病，常累及心血管、肾脏及神经系统；以及由酸性鞘磷脂酶（Acid sphingomyelinase，ASM）缺陷引发脂质在溶酶体内积累的Niemann-Pick病，以单核巨噬细胞系统及神经系统中鞘磷脂蓄积为特征。 02 神经退行性疾病神经元对蛋白质质量控制系统高度依赖，因此，溶酶体功能障碍对神经系统影响尤为显著。在阿尔茨海默病中，自噬体生成增加但溶酶体降解能力下降，导致未降解底物在神经元内积累并诱导细胞死亡。类似的自噬通量阻滞现象也见于帕金森病及其他突触核蛋白病中。α-突触核蛋白的异常聚集不仅是帕金森病的标志性病理特征，也会进一步损伤溶酶体膜稳定性，形成恶性循环。多个溶酶体相关基因（如GBA与TMEM175）的突变已被证实是帕金森病的重要遗传风险因素。此外，溶酶体定位与运输异常也会影响自噬效率，有研究通过高通量筛选获得的化合物可促进溶酶体在微管组织中心附近聚集，从而增强自噬体与溶酶体融合并改善帕金森病模型中的蛋白清除。 03 心血管疾病在动脉粥样硬化中，巨噬细胞吞噬脂质后需依赖溶酶体降解胆固醇酯并生成代谢底物。溶酶体功能受损会导致脂质堆积和泡沫细胞形成，从而加速斑块进展。溶酶体通过调节mTORC1与TFEB信号，参与免疫细胞的代谢重编程与炎症反应调控。免疫研究进一步表明，溶酶体不仅参与抗原加工，还通过代谢调控影响T细胞与巨噬细胞的功能状态，显示其在先天与适应性免疫中的双重作用。 04 癌症溶酶体在癌症中的作用则呈现双重性。一方面，增强的自噬-溶酶体通路可帮助肿瘤细胞在缺氧与营养匮乏条件下存活；另一方面，溶酶体膜通透性增加又可触发细胞死亡。近期研究表明，在蛋白激酶B（AKT）高活化肿瘤中，TRPML1介导的溶酶体外排能够清除脂质过氧化物，从而抑制铁死亡并促进肿瘤生长。 ☆☆☆☆☆☆☆☆☆ 【参考资料】 1. Riederer E, Cang C, Ren D. Lysosomal ion channels: what are they good for and are they druggable targets? Annu Rev Pharmacol Toxicol, 2023, 63: 19-41. 2. Zhu X, Ping M, Liu H, et al. Structural insights into the activation of TMEM175 by small molecule. Neuron, 2025, 113(21): 3567-3581.e9. 3. Zhao L, Zhao J, Zhong K, et al. Targeted protein degradation: mechanisms, strategies and application. Signal Transduct Target Ther, 2022, 7(1): 113. 4. Zhang D, Duque-Jimenez J, Facchinetti F, et al. Transferrin receptor targeting chimeras for membrane protein degradation. Nature, 2025, 638(8051): 787-795. 5. Xiao D, Dong J, Xie F, et al. Polyvalent folate receptor-targeting chimeras for degradation of membrane proteins. Nat Chem Biol, 2025, 21(11): 1731-1741. 6. 丁香园Insight数据库, 检索日期: 2026年3月20日. 本文其它内容请见《全球药物创新快讯》2026年第2期（总第159期）。

2026-03-24

·SM4Life

2026，戈谢病新药突破，III型戈谢病治愈，未来可期

戈谢病（Gaucher disease, GD）是一种罕见的常染色体隐性遗传溶酶体贮积病，其核心致病机制为GBA基因突变，导致体内β-葡萄糖脑苷脂酶活性不足，底物葡萄糖脑苷脂无法正常分解，进而在肝、脾、骨髓等多器官的巨噬细胞内蓄积，形成特征性“戈谢细胞”，最终引发多系统损害。根据是否累及神经系统，戈谢病主要分为3种分型，分别为I型（非神经病变型）、II型（急性神经病变型）、III型（慢性神经病变型），其中I型最为常见，约占所有病例的90%以上。目前，戈谢病的临床治疗体系已趋于成熟，主要分为酶替代疗法（ERT）和底物减少疗法（SRT）两大类，多款药物已在全球及中国获批上市，可有效缓解患者病情、改善生活质量。酶替代疗法是戈谢病的经典治疗方式，通过静脉输注，为患者补充体内缺失的β-葡萄糖脑苷脂酶，直接分解体内蓄积的底物，从而缓解肝脾肿大、贫血等非神经系统症状。通常，此类药物无法穿透血脑屏障，对II型、III型患者的神经系统症状改善作用有限。伊米苷酶（商品名：思而赞）由健赞公司研发，用重组DNA技术制造的β-葡萄糖脑苷脂酶生物类似药，于1994年获得美国FDA批准，目前已在国内进口获批，适用于I型戈谢病的治疗；维拉苷酶α(VPRIV，Velaglucerase-α)由Shire公司研发的水解溶酶体葡糖脑苷脂特异性酶，作为戈谢病1型患者的长效酶替代疗法，于2010年2月被美国食品药品管理局（FDA）批准使用，2021年于我国上市。他利苷酶α（Taliglucerase-α，Elelyso）是由以色列Protalix公司和Pfizer（辉瑞）开发的用于治疗戈谢病的重组葡萄糖脑苷脂酶生物制剂，于2012年5月，美国FDA获批准用于成人戈谢病。维拉苷酶β（商品名：戈芮宁®），中国首个本土自主研发的ERT药物，于2025年5月获得中国NMPA批准，适用于I型和III型戈谢病，显著提升了国内患者的药物可及性。与酶替代疗法不同，底物减少疗法通过口服药物抑制葡萄糖脑苷脂的合成，从源头减少底物蓄积，其适用范围更广，且口服给药方式更为便捷，可有效提升患者用药依从性。米格鲁特（Miglustat，OGT 918，商品名：Zavesca）由英国Oxford GlycoSciences研发的一种口服小分子药物，于2003年7月获得美国FDA批准上市，用于轻中度成人I型戈谢病的治疗，特别是酶替代疗法无效的I型戈谢病治疗；2016年进口注册至中国，用于成人及儿童C型尼曼匹克病患者的进行性神经症状的治疗。依鲁司他（Eliglustat，商品名Cerdelga）是一种口服葡萄糖神经酰胺合成酶抑制剂，属于戈谢病底物减少疗法（SRT）药物，由Genzyme公司研发、赛诺菲收购后推广，2014 年获 FDA 批准上市，适用于经 CYP2D6 基因分型确认的 1 型戈谢病成年患者。国内首仿Eliglustat（艾格司他）于2022年获得中国NMPA批准生产，适用于成人I型戈谢病的治疗，为患者提供了更为便捷的治疗选择；现有治疗方案虽可有效控制I型戈谢病患者的病情，但针对II型、III型患者的神经系统病变，仍存在明显治疗空白。目前，全球戈谢病新药研发领域迎来重大突破，多款针对性药物有望填补治疗空白，改善患者预后。 Venglustat（万格司他）由赛诺菲研发的一款口服葡糖神经酰胺合成酶抑制剂（GCSi），具备穿越血脑屏障的能力，通过抑制异常糖鞘脂（GSL）积累及其相关病理过程，从而延缓疾病进展。该药物于2026年3月18日获得美国FDA突破性疗法认定，专门用于治疗III型戈谢病的神经系统症状，有望成为全球首个针对性治疗该类症状的获批药物，是2026年戈谢病研发领域的重要突破。 III期LEAP2MONO研究数据显示，患者接受Venglustat治疗52周后，两项核心神经功能评估指标均达到统计学显著改善，其对全身脏器及血液学指标的控制效果与现有标准治疗相当，且安全性良好。赛诺菲计划于2026年内推进该药物的全球监管申报，一旦获批，将彻底改变III型戈谢病的治疗格局。除Venglustat外，全球范围内还有多款戈谢病新药处于不同研发阶段，涵盖多个治疗方向，包括基因治疗、小分子靶向药、双特异抗体、核酸疗法、干细胞等。FLT201是Spur Therapeutics公司研发的用于治疗Ⅰ型戈谢病的在研AAV基因疗法，第22届WORLDSymposiu年会上，Spur Therapeutics公司公布了FLT201的 I/II期临床研究最新数据。FLT201采用自主研发的肝脏靶向AAVS3载体，搭载经工程化改造、稳定性更高的β-葡萄糖脑苷脂酶变体功能基因，能让患者干细胞内持续补充缺失的葡萄糖脑苷脂酶，高效降解异常贮积的糖脂及毒性代谢物，从根源解决酶缺乏问题，有望实现“一次治疗，长期获益”的治疗目标。本次公布的数据来自GALILEO-1 I/II期试验和GALILEO-2长期随访研究，入组患者均接受过至少2年的ERT/SRT标准治疗。其中4名接受FLT201单次低剂量治疗的患者，均在11周内停用原有疗法，截至2025年11月数据截止日，已持续停药20-26个月。治疗后患者的核心生物标志物和临床指标均获持久改善：溶酶体葡萄糖鞘氨醇在两年随访中显著下降53%-94%；骨髓底物蓄积这一难治问题实现突破，有患者该指标被完全清除；血红蛋白、血小板计数及肝脾体积也均保持改善或稳定，患者彻底摆脱传统疗法的频繁治疗负担。基于优异的 I/II 期数据，Spur公司已启动FLT201的全球多中心III期临床研究，且与美国FDA就单臂试验设计达成共识，该成果有望同时支持药物的加速审批与完全审批，为其早日上市奠定坚实基础。LY-M001由凌意生物开发的中国首个针对I/III型戈谢病的AAV基因治疗药物，采用自主研发的工程化葡萄糖脑苷脂酶GCaseLY，与野生型GCase相比，其稳定性显著提升，同时保持同样低的免疫原性。GCaseLY基因由专有的肝脏特异性启动子驱动，并通过AAV载体递送，兼具增强疗效与卓越安全性。临床前研究表明，LY-M001注射液疗效优于标准疗法，能在肝脏、脾脏、肺脏及骨髓等疾病相关器官中实现有效的底物清除和症状改善。LY-M001于2024年1月先后获得NMPA和美国FDA的新药临床试验（IND）批准，并获得FDA授予的孤儿药资格认定（ODD）与儿科罕见病资格认定（RPDD），目前已启动II期临床试验。 Sharp Therapeutics公司开发的候选药物901，是一种口服小分子药物，旨在增强缺陷型 GCase 酶的活性，使其能够更好地清除戈谢病患者体内积聚的脂肪分子，已完成临床前研究，准备进入IND申报阶段，预计2027年开展首次人体试验，用于治疗GBA酶缺乏相关的溶酶体贮积症，包括戈谢病（Gaucher Disease）与GBA相关帕金森病（GBA-PD）。目前，戈谢病治疗仍面临两大核心挑战：一是现有治疗药物价格昂贵，年治疗费用超百万人民币，全球患者的药物可及性较差；二是II型戈谢病的急性神经病变仍无有效治疗手段，患者预后不佳。相信，未来，随着科研的持续突破，有望实现戈谢病“精准治疗、全面覆盖”的目标，戈谢病治疗也将从“无药可治”发展为“多种疗法并存”的局面，为每一位患者提供有效的治疗方案，改善患者预后及生活质量。往期精选： 1、儿童弗里德里希共济失调（Pediatric Friedreich ataxia）不再是绝症，全球多款新药向临床冲刺！ 2、多囊肾病（ADPKD）治疗药物研发捷报频传：从小分子靶向药到基因疗法 3、遗传性小脑萎缩共济失调症，“2026，即将破冰”：精准分型 + 全球药物研发格局梳理 4、谁在真正逆转衰老？美股“抗衰”概念上市公司底层逻辑大起底！ 5、千亿减肥赛道，礼来的GLP-1/GIP/GCGR布局：从多肽到小分子的战略跃迁！

上市批准并购生物类似药

2026-03-20

·Pharmaceutical Technology

Congruence secures $39.5m to advance small molecule correctors pipeline

Congruence aims to submit CTA/IND applications for the programmes in early 2027. Credit: Minerva Studio / Shutterstock.com. Congruence Therapeutics has announced the completion of a $39.5m financing round to advance its portfolio of small molecule correctors into the clinic. The portfolio includes programmes targeting melanocortin 4 receptor (MC4R)-deficient genetic obesity, glucocerebrosidase 1 (GBA1)-driven Parkinson’s disease, and Alpha-1 antitrypsin deficiency. The financing was co-led by Dimension and OrbiMed, with additional participation from Amplitude Ventures, BDC Capital’s Thrive Venture Fund, Driehaus, FSTQ, Investissement Quebec, Lumira and Silver Arc. It will primarily fund the Phase I/Ib study of CGX-926, Congruence Therapeutics’ lead programme for MC4R-deficient genetic obesity, enrolling both healthy subjects and patients. Congruence Therapeutics also plans to complete investigational new drug (IND)-enabling activities for two development candidates focused on GBA1-driven Parkinson’s disease and Alpha-1 antitrypsin deficiency. The company aims to submit clinical trial application (CTA) / IND applications for these programmes in early 2027. Congruence Therapeutics co-founder and CEO Dr Clarissa Desjardins said: “Our mission is to translate biology, chemistry and protein structural insights into medicines that address disease at its molecular origin. “In addition to CGX-926, we are advancing multiple proprietary and collaborative programmes. We thank our new and existing investors for their continued support.” Dimension’s founder and managing partner Zavain Dar said: “Leveraging cutting-edge molecular dynamics and machine learning, Congruence has built a best-in-class platform to unlock an exciting modality of medicines in small molecule correctors.” Congruence continues research collaborations, including an expanded multi-target partnership with Ono Pharmaceuticals covering neurology, immunology, and oncology targets. Another collaboration involves drug discovery for a metabolic target with a global pharmaceutical company. The company’s Revenir computational platform analyses dynamic protein states to predict small molecule modulation, supporting its pipeline of genetically validated targets with unmet medical needs.

100 项与维拉苷酶α 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09029	维拉苷酶α	A16AB10	DB06720

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
戈谢病	日本	Takeda Pharmaceutical Co., Ltd.	2014-07-04
I型戈谢病	美国	Takeda Pharmaceuticals U.S.A., Inc.	2010-02-26

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
Ⅲ型戈谢病	临床2期	埃及	Shire Plc	2012-09-14
Ⅲ型戈谢病	临床2期	印度	Shire Plc	2012-09-14
Ⅲ型戈谢病	临床2期	突尼斯	Shire Plc	2012-09-14

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临床结果

适应症

分期

评价

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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


NCT05529992 (CTgov)	临床3期	I型戈谢病	20	VPRIV (VPRIV)	積鏇壓夢鑰淵齋鏇糧膚 = 齋襯襯鹹選艱餘選蓋獵鏇獵積積遞醖製選繭蓋 (築鹹簾願願觸夢獵襯蓋, 簾選簾積壓艱觸壓獵獵 ~ 獵窪艱製鏇網簾願遞壓) 更多	-	2025-02-26
NCT05529992 (CTgov)	临床3期	I型戈谢病	20	Velaglucerase Alfa (Velaglucerase Alfa)	鏇簾鑰餘壓積鹽觸膚壓(窪齋鬱範餘醖壓網艱餘) = 鹽願壓壓鏇襯襯鏇鹽鑰製醖餘繭顧範蓋願衊顧 (窪鬱壓獵蓋遞餘鬱構觸, 艱憲選夢鏇鹽夢製繭醖 ~ 壓範鏇襯壓構艱壓淵窪) 更多	-	2025-02-26
NCT02574286 (CTgov)	临床4期	I型戈谢病	21	Vitamin D+Velaglucerase alfa	窪選構膚製衊構鹽衊糧(糧顧鏇築廠網鹹鬱襯鬱) = 獵構膚憲願願積選糧餘遞簾夢鑰鬱繭構築夢網 (選壓願蓋鑰鹹顧憲廠築, 0.394) 更多	-	2022-02-01
NCT01842841 (Pubmed \| Blood Cells Mol Dis) 人工标引	临床3期	戈谢病	5	velaglucerase alfa	齋願糧窪範鬱糧淵夢艱(糧夢襯壓簾壓淵憲蓋網) = Six serious but non-drug-related adverse events were reported. 鏇製襯壓醖網願餘築鑰 (網願鹽餘鑰壓壓廠鬱膚 ) 更多	积极	2016-07-01
NCT01842841 (CTgov)	临床3期	戈谢病	5	VPRIV	獵鹽淵壓範簾鹽衊選糧 = 製製餘壓築網選簾鬱願積齋醖築襯鹹網窪膚鹽 (選餘顧觸淵鹽壓積膚醖, 衊築醖夢鹹淵夢壓衊鹽 ~ 積膚製鹹繭艱製獵鑰醖) 更多	-	2015-12-14
NCT01685216 (CTgov)	临床1/2期	Ⅲ型戈谢病	7	velaglucerase alfa	壓齋衊繭糧夢鏇襯壓製(鬱艱膚範夢憲蓋積鹽製) = 築顧醖窪齋製鏇鏇範鑰壓獵顧艱構蓋獵膚範顧 (淵構襯顧遞製簾衊淵範, 1.213) 更多	-	2015-10-30
NCT01614574 (CTgov)	临床3期	戈谢病	6	VPRIV	憲遞艱獵鬱願齋糧築衊 = 網鹽窪齋艱壓糧淵膚選選齋鏇獵襯醖遞淵鏇鏇 (壓糧衊製網願製餘膚構, 網鏇艱窪膚壓顧襯遞繭 ~ 築構餘築衊鏇壓鬱願鑰) 更多	-	2014-08-04
NCT00635427 (HGT-GCB-044, CTgov)	临床3期	I型戈谢病	95	VPRIV® (VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034))	鬱衊鑰醖遞遞淵廠範遞 = 蓋網齋遞遞膚膚鏇繭憲鏇衊艱鑰夢齋醖膚淵顧 (簾醖蓋襯構衊遞繭餘築, 遞襯淵簾鏇願積蓋餘積 ~ 網齋鑰製製繭簾衊積夢) 更多	-	2014-01-28
NCT00635427 (HGT-GCB-044, CTgov)	临床3期	I型戈谢病	95	VPRIV® (VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039))	廠選鹹鹽製醖構觸窪獵(襯艱憲糧鹽襯鹹鬱鬱廠) = 鏇艱簾餘獵簾簾醖壓觸蓋築廠願鑰齋淵鑰膚鏇 (構齋淵窪構糧築鏇壓網, 積鏇觸獵廠壓鹹夢膚積 ~ 繭蓋繭夢艱積廠願鑰夢) 更多	-	2014-01-28
Pubmed \| Am J Hematol	临床2/3期	I型戈谢病	40	Velaglucerase alfa	積蓋網鏇膚選糧顧製膚(艱顧築糧醖選窪壓壓鹽) = 9 of 40 patients 鏇鬱網鏇顧憲鏇願簾膚 (觸積襯鏇繭襯淵簾選願 ) 更多	-	2013-03-01
NCT00553631 (CTgov)	临床3期	I型戈谢病	34	imiglucerase	窪遞膚網襯鏇鬱願齋膚(壓積蓋鹹積衊範膚範艱) = 衊獵衊觸獵鹽鑰遞鬱築築遞鏇顧鏇廠繭構築衊 (顧壓積淵糧壓繭簾獵獵, 0.281) 更多	-	2011-01-04
NCT00430625 (CTgov)	临床3期	I型戈谢病	25	VPRIV (VPRIV® (60 U/kg, IV, Every Other Week))	顧選繭壓蓋鬱鬱獵範廠(鹹範積淵簾網廠衊憲憲) = 憲窪選願窪糧製繭餘餘襯膚簾壓艱繭廠膚窪鹽 (窪醖鹽窪衊遞淵遞簾鏇, 積積遞廠餘壓廠願糧獵 ~ 獵積夢鏇範製襯鑰簾構) 更多	-	2010-09-10
NCT00430625 (CTgov)	临床3期	I型戈谢病	25	VPRIV (VPRIV® (45 U/kg, IV, Every Other Week))	蓋艱顧淵製簾淵鏇膚壓(蓋築壓積選壓構鬱選壓) = 簾構繭襯襯簾鹹顧餘蓋顧築範憲範網夢獵鹹繭 (選鹽遞窪鹹蓋艱獵簾齋, 餘簾衊製構範蓋顧繭網 ~ 餘遞艱鑰顧夢築膚鏇衊) 更多	-	2010-09-10