更新于：2024-11-01

Hyperoxaluria, Primary

原发性高草酸尿症

更新于：2024-11-01

基本信息

别名

Congenital oxaluria、Hyperoxaluria, Primary、Hyperoxalurias, Primary

+ [38]

简介

A genetic disorder characterized by excretion of large amounts of OXALATES in urine; NEPHROLITHIASIS; NEPHROCALCINOSIS; early onset of RENAL FAILURE; and often a generalized deposit of CALCIUM OXALATE. There are subtypes classified by the enzyme defects in glyoxylate metabolism.

关联

项与原发性高草酸尿症相关的药物

Nedosiran

靶点

LDHA

作用机制

LDHA抑制剂

在研机构

Dicerna Pharmaceuticals, Inc. [+1]

原研机构

Novo Nordisk, Inc.

在研适应症

原发性高草酸尿症1型 [+3]

非在研适应症-

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2023-09-29

Lumasiran sodium

靶点

GOX

作用机制

GOX刺激剂 [+1]

在研机构

Alnylam Netherlands BV [+2]

原研机构

Alnylam Pharmaceuticals, Inc.

在研适应症

原发性高草酸尿症1型 [+1]

非在研适应症

草酸钙肾石病

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2020-11-19

Stiripentol

司替戊醇

靶点

GABAA receptor x L-lactate dehydrogenase

作用机制

GABAA receptor激动剂 [+1]

在研机构

Biocodex SAS [+3]

原研机构

Biocodex SAS

在研适应症

CDKL5缺乏症 [+7]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2007-01-03

项与原发性高草酸尿症相关的临床试验

NCT06465472 / Not yet recruiting临床3期

Evaluation of the Efficacy and Safety of Stiripentol in Patients 6 Years and Older With Primary Hyperoxaluria Type 1, 2 or 3

Evaluation of the efficacy and safety of stiripentol in patients 6 years and older with primary hyperoxaluria type 1, 2 or 3.

开始日期2024-08-01

申办/合作机构

Biocodex SAS

[+1]

NCT06511349 / Recruiting早期临床1期IIT

Clinical Exploration Study of YOLT-203 in the Treatment of Type 1 Primary Hyperoxaluria (PH1)

This study is a single-arm, open-label, single-dose, dose-escalation trial, aiming to evaluate the safety and tolerability of YOLT-203 in the Chinese population with type 1 primary hyperoxaluria (PH1); and to preliminarily assess the effect of a single dose of YOLT-203 on the plasma oxalate level.
In this study, the maximum screening period of the main study is 60 days, the treatment day is Day 1 (D1), and the safety follow-up period is up to Week 52 after administration. In addition, subjects within the first dose group can voluntarily receive a second treatment with the test drug at the effective dose level.
After the end of the main study, the subjects will undergo long-term follow-up. According to the requirements of the "Technical Guidelines for Long-Term Follow-up Clinical Studies of Gene Therapy Products (Trial)" issued by the CDE, the long-term follow-up is up to 15 years after administration.

开始日期2024-07-12

申办/合作机构

上海交通大学医学院附属仁济医院

NCT06225882 / RecruitingN/AIIT

Retrospective and Prospective Follow-up of Patients With Primary Hyperoxaluria Type 1 Treated With Lumasiran in France - DAILY-LUMA

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by mutation in the AGXT gene encoding the hepatic peroxisomal enzyme AGT. Reduced AGT activity results in increased glyoxylate and oxalate production, causing the formation of kidney stones, nephrocalcinosis and renal failure. Clinical trials of Lumasiran have provided information on the efficacy and safety of Lumasiran in the treatment of primary hyperoxaluria type 1. However, they do not provide data on long-term efficacy, safety and patient management. As part of the post-marketing follow-up of Lumasiran, in agreement with the authorities, this study proposes a retrospective and prospective follow-up over 5 years of pediatrics and adults patients treated in France with a standardized clinical, biological and radiological follow-up. The main objective is to monitor the evolution of PH1 parameters and particularly oxaluria before and after treatment.

开始日期2023-01-01

申办/合作机构

Hospices Civils de Lyon

100 项与原发性高草酸尿症相关的临床结果

登录后查看更多信息

100 项与原发性高草酸尿症相关的转化医学

登录后查看更多信息

0 项与原发性高草酸尿症相关的专利（医药）

登录后查看更多信息

1,915

项与原发性高草酸尿症相关的文献（医药）

2024-12-31·Renal Failure

Second transplantation after kidney graft loss in primary hyperoxaluria type 2: a pedigree study and mutation analysis

Article

作者: Hui, Jialiang ; Xiong, Fu ; Zhang, Mingming ; Zheng, Yingchun ; Xia, Renfei ; Zeng, Wenli ; Xu, Jian ; Luo, Jia ; Fang, Yiling ; Deng, Wenfeng ; Peng, Yushi ; Miao, Yun ; Wang, Yuchen

BACKGROUNDPrimary hyperoxaluria type 2 (PH2) is a rare disorder caused by GRHPR mutations. Research on the mutation spectrum and pedigree of PH2 helps in comprehending its pathogenesis and clinical outcomes, guiding clinical diagnosis and treatment.METHODSWe report a case of PH2 with a three-generational pedigree. The GRHPR genotypes of the family members were confirmed by Sanger sequencing. Urine and blood samples were collected for biochemical analysis. Computational analysis was performed to assess the pathogenicity of the mutations. Cellular experiments based on site-directed mutagenesis were conducted to confirm the effect of mutations on GRHPR expression, activity, and subcellular localization.RESULTSThe proband underwent her first kidney transplantation in 2015, and experienced recurrent urinary tract infections and urolithiasis postoperatively. Graft failure occurred in 2018. Whole exome sequencing identified compound heterozygous GRHPR mutations p.G160E/p.P203Rfs*7. The patient underwent a second kidney transplantation in 2019 and maintained good graft function with urine dilution measures. Notably, her brother and sister carried the same mutations; however, only the proband progressed to renal failure. Computational analysis suggested that p.G160E reduced the affinity of GRHPR for coenzymes. Cellular experiments indicated that p.G160E reduced GRHPR activity (p < 0.001), whereas p.P203Rfs*7 not only suppressed expression (p < 0.001) and reduced activity (p < 0.001), but also facilitated protein aggregation. Based on our results, the variant p.G160E was classified as 'pathogenic' according to ACMG guidelines.CONCLUSIONSOur findings suggest that treatment strategies for the long-term prevention of oxalate nephropathy should be developed for patients with PH2 receiving isolated kidney transplantation. Moreover, the pathogenicity of the compound heterozygous GRHPR mutations p.G160E/p.P203Rfs*7 was also validated.

2024-12-01·Pediatric Nephrology

Recurrent symptomatic urolithiasis in a patient with cystic fibrosis

Article

作者: Köse, Mehmet ; Dündar, Munis ; Poyrazoglu, Muammer Hakan ; Yel, Sibel ; Dursun, Ismail ; Kiraz, Aslıhan

AbstractA 6-month-old girl, previously diagnosed with cystic fibrosis (CF), was admitted to hospital for nephrolithiasis. Her parents were first-degree cousins. The patient underwent endoscopic stone management. Despite no family history of stones and medical treatment with potassium citrate, the patient developed recurrent renal stones and atypical urinary tract infections during follow-up. Basic investigations were all normal. Due to consanguinity and early presentation of nephrolithiasis, metabolic causes such as cystinuria and hyperoxaluria were considered. Cystinuria was excluded due to normal cystine levels. High urinary oxalate excretion was found as expected due to absorptive (secondary) hyperoxaluria in CF patients. An early stone burden in the patient with a history of medical treatment and consanguinity led us to perform a genetic testing. Genetic testing revealed a missense homozygous variant in exon 1 of the AGXT gene. The patient was diagnosed with primary hyperoxaluria type 1. Two rare life-threatening genetic diseases were found together in the same child.

2024-12-01·American Journal of Ophthalmology Case Reports

Late-onset retinal oxalosis in primary hyperoxaluria type 2

Article

作者: Bhuyan, Rupak ; Thomas, Christie ; Boyce, Timothy ; Maggio, Tyler ; Sambharia, Meenakshi ; Gehrs, Karen

PurposeTo report a previously undescribed case of late-onset vision loss due to retinal oxalosis in a patient with primary hyperoxaluria type 2 (PH2).ObservationsAn 82-year-old female with a history of biopsy-proven oxalate nephropathy developed vision loss 8 months after end stage kidney disease. She developed progressive retinal ischemia secondary to crystal deposition. She was presumed to have retinal oxalosis, and genetic testing confirmed PH2. Her retinopathy occurred once renal clearance fellow below hepatic oxalate production. The only effective treatment is kidney transplantation, but this patient was not a candidate.Conclusions and ImportanceTo date, this is the most delayed-onset and severe reported case of progressive ischemic retinopathy from PH2. Patients with systemic oxalosis should be referred for genetic testing, as there are new RNA interference treatments approved for other subtypes of primary hyperoxaluria.

178

项与原发性高草酸尿症相关的新闻（医药）

2024-10-22

·GlobeNewswire-Health Care

Arbor Biotechnologies to Highlight New Preclinical Data Supporting Advancement of Pipeline Programs and Knock-In Applicability of Type V Nucleases at Upcoming Medical and Scientific Meetings

Oral presentation at ASN on lead program, ABO-101 for primary hyperoxaluria type 1 (PH1), supporting in vivo proof of pharmacology. On-track for year-end IND/CTA filing.Oral presentation at ALS One and a poster presentation at ESGCT on lead ALS program ABO-202, highlighting in vivo reversal of ALS-associated STMN2 aberrant splicing and phenotypic outcomes in human motor neurons.Poster presentation at ESGCT demonstrating targeted gene knock-in and broader applicability of type V nuclease platform for monogenic diseases. CAMBRIDGE, Mass., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Arbor Biotechnologies, Inc., a biotechnology company discovering and developing the next generation of genetic medicines, today announced oral and poster presentations on pipeline and early discovery programs at upcoming medical and scientific meetings: American Society of Nephrology (ASN) 2024 Kidney Week Meeting, October 23-27 in San Diego, California31st Annual European Society of Gene and Cell Therapy (ESGCT), October 22-25 in Rome, ItalyALS One 7th Annual ALS Research Symposium, November 13-15, Virtual At ASN Kidney Week, Arbor will present in vivo non-human primate (NHP) proof-of-pharmacology data supporting continued development of ABO-101, its most advanced gene editing therapeutic candidate designed to address primary hyperoxaluria type 1 (PH1) through inactivation of the HAO1 gene in the liver. Arbor is on track to file the IND/CTA for ABO-101 in PH1 by year-end. At the ALS One 7th Annual ALS Research Symposium and at ESGCT, Arbor will detail data on its lead ALS program ABO-202, supporting genetic disruption of STMN2, preventing errors in the processing of its mRNA, and elucidating a path towards proof of concept for a therapeutic CRISPR gene editing approach for the treatment of amyotrophic lateral sclerosis (ALS). The company will also showcase novel data at ESGCT demonstrating targeted gene knock-in at an endogenous promoter achieving equivalent or improved knock-in efficiency when compared to type II nucleases. This data supports the efficiency and breadth of applicability of Arbor’s type V nucleases to monogenic diseases. Details for the presentations are as follows: ASN 2024 Kidney Week:Oral Presentation Title: Development of ABO-101, A Novel Gene Editing Therapy for Primary Hyperoxaluria Type 1 Session Date and Time: Thursday, October 24, 2024, 4:30-6:00pm PDT Location: Room 23, Convention Center Presenter: Winston Yan, MD, PhD Abstract Number: TH-OR88 ESGCT 2024:Poster Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: Poster Session 1, October 22, 7:30-9:00pm CEST Location: Forum, La Nuvola Presenter: Chee Yeun Chung, PhD Abstract Number: P0327 Poster Title: Targeted Knock-In at the Human TTR Locus Using Type V Nucleases Session Date and Time: Poster Session 3, October 24, 2:00-3:30pm CEST Location: Concourse Level 1 and Mezzanine Concourse, La Nuvola Presenter: Whitney J. French, PhD Abstract Number: P0603 ALS One 7th Annual ALS Research Symposium:Oral Presentation Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: November 14, 3:40-4:00pm EDT Presenter: Priscilla D. Negraes, PhD About Arbor Biotechnologies, Inc.Arbor BiotechnologiesTM, a next-generation gene editing company based in Cambridge, MA, is advancing a pipeline of novel gene editing therapeutics to address a wide range of genetic conditions - from the ultra-rare to the most common genetic diseases. Our unique suite of optimized gene editors goes beyond the limitations of early editing technologies to unlock access to new gene targets and has fueled a robust pipeline of first-in-class assets focused on diseases of high unmet need. We are rapidly advancing our lead program in primary hyperoxaluria type 1 to the clinic and focusing our research and development efforts on genomic diseases of the liver and CNS for which there are no existing functional cures. For more information, please visit: arbor.bio Media Contact:Peg RusconiDeerfield Groupprusconi@deerfieldgroup.com

基因疗法临床研究

2024-10-04

·药时代

原来诺贝尔奖就在我们身边，从未走远！（投票预测2024年诺贝尔生理学或医学奖）

明天上午9点，2024年诺奖预测，药时代直播间见！正文共： 3679字 16图预计阅读时间： 10分钟（图片来源：诺奖官网）诺贝尔奖，这个代表着科学界最高荣誉的名字，它的成果不仅在学术界享有盛誉，更在不知不觉中走进了我们的日常生活，并非与我们十万八千里遥不可及。今天，就让我们一起来探索那些与我们息息相关的诺贝尔奖成果，看看它们是如何在医疗领域发挥着重要作用，如何呵护着你我他的健康。 1. 胰岛素（1923年诺贝尔生理学或医学奖）代表药物：胰岛素早在1923年，加拿大科学家弗雷德里克·班廷和查尔斯·贝斯特就因发现胰岛素而获得诺贝尔生理学或医学奖。胰岛素是调节血糖水平的关键激素，对于糖尿病患者来说，胰岛素的发现和提纯是革命性的。它使得1型糖尿病患者能够通过注射胰岛素来控制血糖，极大地改善了他们的生活质量和预期寿命。 2. 改变寄生虫疾病治疗的发现（2015年诺贝尔生理学或医学奖）代表药物：青蒿素、阿维菌素 2015年诺贝尔生理学或医学奖表彰了两项革命性的发现：中国科学家屠呦呦从青蒿中提取的青蒿素，以及爱尔兰和日本科学家发现的阿维菌素。青蒿素的发现为治疗疟疾提供了新途径，有效降低了疟疾死亡率。阿维菌素则对抗盘尾丝虫病和淋巴丝虫病有显著效果，两者的发现彻底改变了寄生虫疾病的治疗方式。 3. HPV病毒感染引起宫颈癌（2008年诺贝尔生理学或医学奖）代表疗法：宫颈癌疫苗 2008年，科学家因揭示HPV（人乳头状瘤病毒）感染与宫颈癌之间的联系而获得诺贝尔生理学或医学奖。这一发现促成了HPV疫苗的开发，这是人类历史上第一个用于预防癌症的疫苗，对女性健康产生了重大影响。 4. RNA干扰现象（2006年诺贝尔生理学或医学奖）代表疗法：RNAi疗法 2006年，科学家因发现RNA干扰现象而获得诺贝尔生理学或医学奖。RNA干扰技术为治疗基因变异引起的疾病提供了新的思路。2018年，首款RNAi疗法Onpattro（patisiran）在美国获批，用于治疗遗传性转甲状腺素蛋白淀粉样变性引起的周围神经疾病，标志着RNAi疗法在临床应用上迈出了重要一步。目前，全球已有数款RNAi疗法获批上市，其中包括： Patisiran (Onpattro®)：由Alnylam Pharmaceuticals开发，用于治疗遗传性转甲状腺素蛋白淀粉样变性多发性神经病（hATTR-PN），是全球首款获得FDA批准的RNAi疗法。 Givosiran (Givlaari®)：同样由Alnylam开发，用于治疗急性肝卟啉病（AHP）。 Lumasiran (Oxlumo®)：用于治疗原发性高草酸尿症1型（PH1）。 Inclisiran (Leqvio®)：由Novartis开发，用于治疗高胆固醇血症，通过抑制PCSK9基因的表达，降低低密度脂蛋白胆固醇（LDL-C）水平。 Vutrisiran：用于治疗遗传性转甲状腺素蛋白淀粉样变性（hATTR），目前正在进行III期临床试验。 Fitusiran：用于治疗血友病，通过靶向抗凝血酶（AT）来增加凝血因子水平。 Nedosiran：用于治疗原发性高草酸尿症，通过靶向LDH基因来减少草酸盐的生成。此外，在中国，心血管疾病患者迎来了首个针对慢病领域的siRNA药物英克司兰（商品名：乐可为）的上市，用于治疗动脉粥样硬化性心血管病（ASCVD）。这些疗法的成功上市标志着RNAi技术在医学治疗上的应用潜力，为多种疾病的治疗提供了新的策略和方法。 5. 免疫检查点蛋白的发现（2018年诺贝尔生理学或医学奖）代表疗法：抗CTLA-4抗体、抗PD-1/PD-L1抗体 2018年，诺贝尔生理学或医学奖颁给了CTLA-4和PD-1的发现者。这一发现为癌症免疫疗法领域带来了革命性的变化。以抗CTLA-4抗体、抗PD-1抗体为代表的免疫疗法，通过解除癌细胞的“踩刹车”系统，为癌症患者带来了新的治疗希望。 6. “噬菌体展示”技术（2018年诺贝尔化学奖）代表药物：阿达木单抗 1985年诞生的“噬菌体展示”技术在2018年荣获诺贝尔化学奖。该技术通过在噬菌体表面展示外源基因编码的蛋白质，筛选出具有特定功能的蛋白质。此方法不仅促进了抗体药物的发展，还催生了如修美乐（阿达木单抗）等治疗免疫疾病的药物，为全球患者带来了福音。 7. 氧感知通路（2019年诺贝尔生理学或医学奖）代表药物：罗沙司他、belzutifan、daprodustat 2019年，科学家因在氧感知通路研究领域做出重要贡献而获得诺贝尔生理学或医学奖。这一发现对创新药的研发颇具意义，比如通过调控低氧诱导因子-1（HIF-1）通路，促进红细胞的生成，有望治疗贫血。此外，基于氧感知通路的创新疗法，如罗沙司他、belzutifan、daprodustat等，已在治疗贫血、VHL疾病相关癌症等方面取得了显著成效。 8. 丙型肝炎病毒的发现（2020年诺贝尔生理学或医学奖）代表药物：针对丙肝的抗病毒类药物 2020年，三位科学家因发现丙型肝炎病毒而获此殊荣。这一发现不仅使得血液检查成为可能，有效预防了输血后肝炎的发生，还推动了针对丙肝的抗病毒治疗药物的研发，使得丙肝成为历史上第一个可以治愈的慢性肝炎。这些诺贝尔奖的成果，不仅仅是科学界的荣耀，更是我们每一个人的健康守护者。它们让我们深刻感受到，科学的力量就在我们身边，从未走远。还有很多获得诺贝尔奖殊荣的科学研究正在被开发成药物、疗法的过程中，这些药物、疗法很有可能在不远的将来获批上市，惠及你我他。下面举几个例子。泛素-蛋白酶体系统（2004年诺贝尔化学奖）代表疗法：靶向蛋白降解药物泛素-蛋白酶体系统是细胞内蛋白质降解的主要途径，参与了80%以上的蛋白质降解。2004年诺贝尔化学奖表彰了这一系统发现，它为疾病治疗提供了新思路。靶向蛋白降解药物利用泛素-蛋白酶体系统，有望攻克传统药物无法解决的蛋白质功能失调问题。目前，科学家正在开发这类药物，以治疗癌症、自身免疫性疾病等，为“不可成药”的蛋白质提供了新的治疗策略。难成药靶点蛋白降解研究进展和技术交流 | 药时代直播间将成熟细胞重新“编程”（2012年诺贝尔生理学或医学奖）代表疗法：诱导多能干细胞疗法诱导多能干细胞（iPSC）疗法是一种革命性的技术，它将成熟细胞重新编程为早期干细胞状态。2012年诺贝尔生理学或医学奖表彰了这一发现。iPSC技术为治疗多种疾病提供了新途径，包括炎症、自身免疫疾病、心衰、脑卒中、帕金森病、糖尿病和遗传性疾病。尽管目前iPSC疗法大多处于临床试验阶段，但已有一些研究取得积极进展，预示着未来可能有更多的iPSC疗法获批上市。囊泡运输的调节机制（2013年诺贝尔生理学或医学奖）代表疗法：外泌体疗法外泌体疗法是一种利用外泌体（Exosomes）——一种由细胞释放的微小囊泡，携带蛋白质、RNA等生物分子，进行细胞间通讯和物质运输的特性，来实现治疗目的的新兴治疗手段。外泌体疗法在多个领域展现出了巨大的潜力，包括但不限于肿瘤治疗、组织修复、免疫调节等。2013年诺贝尔生理学或医学奖授予了发现细胞内主要运输系统的囊泡转运调控机制的科学家，这一发现为外泌体疗法的研究和应用提供了重要的理论基础。目前，已有一些外泌体疗法处于临床试验阶段，例如Codiak BioSciences公司的exoSTING和exoIL-12，以及Kimera Labs的胎盘细胞系衍生的间充质干细胞外泌体（MSC-Exo）。随着研究的深入和技术的发展，预计未来会有更多基于外泌体的疗法获批上市，为多种疾病的治疗提供新的解决方案。 2021年开始，药时代与返朴等合作伙伴联手，连续三年共同举办诺奖预测直播，特别邀请多年来对诺贝尔奖背后科学史深度钻研的徐亦迅博士主讲，受到广大朋友们的关注和好评。今年合作继续，而且参加的媒体阵容更加强大。直播将于2024年10月5日（星期六）上午9点开始。现在，我们邀请广大朋友们对今年的诺贝尔生理学或医学奖进行预测。欢迎大家无记名投票！参考资料：10类诺贝尔奖级创新疗法公布！（医药观澜）谁能获得今年的诺贝尔奖？（药明康德）药时代文章、视频其它公开资料封面图来源：网络版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 十年上市20款重磅创新药！169页罗氏制药研发日PPT展望十年雄心壮志（可下载）又一个10万+！ 2024年诺贝尔奖即将公布！药时代全程直播官宣实况。徐亦迅博士「赛前」展望诺贝尔生理学或医学奖「金赛药业首届研发日」直播预约通道开启！诚邀观看！重塑癌症诊疗格局，携手共筑健康未来！阿斯利康诚邀合作伙伴，探索联合治疗创新方案点击这里，发现与众不同的商机！

疫苗AHA会议核酸药物临床3期

2024-09-25

·rare disease

双重认定！尧唐生物YOLT-203获得FDA孤儿药（ODD）与罕见儿科疾病（RPDD）资格认定

2024年9月23日，致力于开发创新型体内基因编辑药物的尧唐生物（YolTech Therapeutics）宣布，美国食品药品监督管理局（FDA）已授予公司在研基因编辑药物YOLT-203孤儿药资格认定（Orphan Drug Designation, ODD），用于治疗原发性高草酸尿症1型（PH1）。 FDA在审查尧唐生物提交的申请后，确认该药物适用于治疗原发性高草酸尿症（PH），并认为尧唐生物提出的有关PH1的指定属于这一更广泛的疾病范围之内。此前，YOLT-203已获得FDA儿科罕见疾病资格认定（RPDD），此次ODD认证进一步巩固了该药物在罕见病治疗领域的潜力与重要性。 YOLT-203采用尧唐生物自主研发的CRISPR/Cas基因编辑工具YolCas12™，通过脂质纳米颗粒（LNP）递送，靶向纠正AGXT基因中的突变，旨在降低患者体内有害草酸盐的生成，从而减轻对肾脏及其他器官的损害。这一创新疗法不仅是全球首个用于治疗PH1的体内基因编辑药物，也是全球范围内首个针对儿科罕见病的体内基因编辑临床试验。｜关于原发性高草酸尿症（PH）原发性高草酸尿症（Primary Hyperoxaluria, PH）是一种罕见的常染色体隐性遗传病，由肝脏中负责草酸盐代谢的酶缺陷引起，导致体内草酸盐生成过多并沉积。PH1是最常见的亚型，由AGXT基因突变引起，是一种儿童期发病的常染色体隐性遗传病。患者常表现为肾结石、肾钙化、肾功能不全，以及其他器官的草酸盐沉积。严重病例可能发展为终末期肾病（ESRD），需进行透析、肾移植或肝肾联合移植。PH主要影响儿童，症状通常在0-3岁之间显现。如果未得到有效干预，大多数患者会在青少年时期发展为终末期肾病，严重威胁生命。该疾病的发病率估计为1/58,000，在美国和欧盟约有一万人受到影响，中国则有超过两万名患者。｜关于YOLT-203 YOLT-203是尧唐生物自主研发的新一代体内基因编辑药物，采用了具有尧唐自主专利的CRISPR/Cas基因编辑工具YolCas12™，通过脂质纳米颗粒（LNP）递送进入肝细胞后，YolCas12™在相应的向导 RNA (gRNA) 的引导下，靶向特定基因，旨在降低血液中有害的草酸水平。2024年8月，YOLT-203启动了由研究者发起的临床试验（IIT），首位成人患者和首位儿童患者分别于8月5日和8月20日接受了首剂治疗。这是全球首个针对 PH1 的体内基因编辑疗法的临床试验，初步临床数据显示，YOLT-203在降低血液中草酸盐水平方面具有良好的潜力，同时兼具安全性。｜关于孤儿药资格（ODD） FDA的孤儿药资格认定（Orphan Drug Designation, ODD）旨在激励开发用于治疗影响少于20万美国患者的罕见疾病药物。获得ODD认定的药物将享有一系列激励措施，包括税收抵免、临床试验费用减免、FDA审评费用豁免以及7年市场独占期。YOLT-203此次获得ODD认证，表明其作为一种创新疗法在罕见病领域的巨大潜力。

孤儿药基因疗法临床研究