更新于：2024-11-01

ABCA4

更新于：2024-11-01

基本信息

别名

ABCA4、ABCR、ARMD2

+ [16]

简介

Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like the 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine from the lumen to the cytoplasmic leaflet of photoreceptor outer segment disk membranes, where N-cis-retinylidene-phosphatidylethanolamine (N-cis-R-PE) is then isomerized to its all-trans isomer (N-trans-R-PE) and reduced by RDH8 to produce all-trans-retinol (all-trans-rol) and therefore prevents the accumulation of excess of 11-cis-retinal and its schiff-base conjugate and the formation of toxic bisretinoid (PubMed:24097981, PubMed:22735453, PubMed:23144455, PubMed:20404325, PubMed:10075733, PubMed:29847635, PubMed:33375396). May display both ATPase and GTPase activity that is strongly influenced by the lipid environment and the presence of retinoid compounds (PubMed:22735453). Binds the unprotonated form of N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP, and ATP binding and hydrolysis induce a protein conformational change that causes the dissociation of N-retinylidene-phosphatidylethanolamine (By similarity).

关联

项与 ABCA4 相关的药物

ACDN-01

靶点

ABCA4

作用机制

ABCA4调节剂

在研机构

Ascidian Therapeutics, Inc.初创企业

原研机构

Ascidian Therapeutics, Inc.初创企业

在研适应症

视锥-视杆营养不良 [+1]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

JWK-006

靶点

ABCA4

作用机制

ABCA4调节剂

在研机构

四川大学华西医院（四川省国际医院） [+1]

原研机构

成都金唯科生物科技有限公司初创企业

在研适应症

斯塔加特病

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

AAVB-039

靶点

ABCA4

作用机制

ABCA4调节剂

在研机构

AAVantgarde Bio Srl初创企业 [+1]

原研机构

AAVantgarde Bio Srl初创企业

在研适应症

斯塔加特病

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

项与 ABCA4 相关的临床试验

NCT06467344 / Recruiting临床1/2期

ACDN-01-001: Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Subretinal ACDN-01 in Participants with ABCA4-related Retinopathy

This study is an open-label, single ascending dose clinical trial in participants who have ABCA4-related retinopathies. This is the first-in-human clinical trial in which ACDN-01 will be evaluated for safety, tolerability, and preliminary efficacy following a single subretinal injection of ACDN-01.

开始日期2024-06-11

申办/合作机构

Ascidian Therapeutics, Inc.初创企业

NCT06300476 / Active, not recruiting临床1/2期IIT

Safety and Efficacy of a Single Subretinal Injection of JWK006 Gene Therapy in Subjects With Stargardt Disease(STGD1)

The purpose of the study is to assess the safety and efficacy of JWK006 in Stargardt Disease(STGD1).
JWK006 is packed by adeno-associated virus vector that expressing ABCA4 gene.

开始日期2023-11-20

申办/合作机构

四川大学华西医院（四川省国际医院）

ChiCTR2300077080 / SuspendedN/AIIT

Clinical study on the safety and efficacy of JWK006 injection administered by a single subretinal injection in one eye in subjects with Stargardt disease type 1

开始日期2023-11-01

申办/合作机构-

100 项与 ABCA4 相关的临床结果

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100 项与 ABCA4 相关的转化医学

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0 项与 ABCA4 相关的专利（医药）

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1,201

项与 ABCA4 相关的文献（医药）

2025-01-01·American Journal of Ophthalmology

Cross-Sectional Analysis of Outer Retinal Tubulation in Inherited Retinal Diseases: A Multicenter Study

Article

作者: Lee, Winston ; Kim, Angela H ; Wu, Wei-Chi ; Wang, Ethan Hung-Hsi ; Wang, Nan-Kai ; Su, Pei-Yin ; Liu, Pei-Kang ; Kang, Eugene Yu-Chuan ; Levi, Sarah R ; Hwang, Yih-Shiou ; Chang, Yo-Chen ; Chen, Kuan-Jen ; Chi, Yi-Chun ; Lin, Pei-Hsuan ; Allikmets, Rando ; Liu, Laura ; Lai, Chi-Chun ; Wu, Pei-Liang ; Jenny, Laura A ; Tsang, Stephen H

PURPOSEThis study aims to explore genetic variants that potentially lead to outer retinal tubulation (ORT), estimate the prevalence of ORT in these candidate genes, and investigate the clinical etiology of ORT in patients with inherited retinal diseases (IRDs), with respect to each gene.DESIGNRetrospective cohort study.METHODSA retrospective cross-sectional review was conducted on 565 patients with molecular diagnoses of IRD, confirming the presence of ORT as noted in each patient's respective spectral-domain optical coherence tomography (SD-OCT) imaging. Using SD-OCT imaging, the presence of ORT was analyzed in relation to specific genetic variants and phenotypic characteristics. Outcomes included the observed ORT frequencies across 2 gene-specific cohorts: non-retinal pigment epithelium (RPE)-specific genes, and RPE-specific genes; and to investigate the analogous characteristics caused by variants in these genes.RESULTSAmong the 565 patients included in this study, 104 exhibited ORT on SD-OCT. We observed ORT frequencies among the following genes from our patient cohort: 100% (23/23) for CHM, 100% (2/2) for PNPLA6, 100% (4/4) for RCBTB1, 100% for mtDNA [100% (4/4) for MT-TL1 and 100% (1/1) for mtDNA deletion], 100% (1/1) for OAT, 95.2% (20/21) for CYP4V2, 72.7% (8/11) for CHM female carriers, 66.7% (2/3) for C1QTNF5, 57.1% (8/14) for PROM1, 53.8% (7/13) for PRPH2, 42.9% (3/7) for CERKL, 28.6% (2/7) for CDHR1, 20% (1/5) for RPE65, 4% (18/445) for ABCA4. In contrast, ORT was not observed in any patients with photoreceptor-specific gene variants, such as RHO (n = 13), USH2A (n = 118), EYS (n = 70), PDE6B (n = 10), PDE6A (n = 4), and others.CONCLUSIONSThese results illustrate a compelling association between the presence of ORT and IRDs caused by variants in RPE-specific genes, as well as non-RPE-specific genes. In contrast, IRDs caused by photoreceptor-specific genes are typically not associated with ORT occurrence. Further analysis revealed that ORT tends to manifest in IRDs with milder intraretinal pigment migration (IPM), a finding that is typically associated with RPE-specific genes. These findings regarding ORT, genetic factors, atrophic patterns in the fundus, and IPM provide valuable insight into the complex etiology of IRDs. Future prospective studies are needed to further explore the association and underlying mechanisms of ORT in these contexts.

2025-01-01·American Journal of Ophthalmology

Progression Rate of Macular Retinal Pigment Epithelium Atrophy in Geographic Atrophy and Selected Inherited Retinal Dystrophies. A Systematic Review and Meta-Analysis

Review

作者: Thiadens, Alberta A H J ; Colijn, Johanna M ; Biarnés, Marc ; Bassil, Fabiana L

PURPOSETo compare the macular retinal pigment epithelium (RPE) atrophy progression rate of selected degenerative and macular inherited retinal diseases (IRD).DESIGNSystematic review and meta-analysis.METHODSThe protocol was registered on the PROSPERO database. Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to September 15, 2023 for articles reporting the RPE atrophy growth rate in treatment-naïve eyes with geographic atrophy (GA), Stargardt disease (STGD1), Best disease, pseudoxanthoma elasticum (PXE), central areolar choroidal dystrophy (CACD), or pattern dystrophies with no previous or current macular neovascularization and a minimum follow-up time of 12 months. Meta-analyses determined mean RPE atrophy growth rates per disease, imaging modality (fundus autofluorescence [FAF], optical coherence tomography [OCT], or color fundus photography [CFP]) and metric (mm²/y or mm/y). The Newcastle-Ottawa scale and the Cochrane Risk-of-Bias tool assessed the risk of bias, and funnel plots were used to evaluate small-study effects.RESULTSFrom 4354 publications, 85 were included for meta-analysis: 69 studies (7815 eyes) on GA, 15 (1367 eyes) on STGD1, and one on both. Two studies on PXE were only eligible for review. No studies for other diseases met our eligibility criteria. The overall mean RPE atrophy growth rate for GA using FAF was 1.65 mm²/y (95% confidence interval [CI], 1.49-1.81) and 0.35 mm/y (95% CI, 0.28-0.41); using OCT, it was 1.46 mm²/y (95% CI, 1.28-1.64) and 0.34 mm/y (95% CI, 0.28-0.40); and on CFP it was 1.76 mm²/y (95% CI, 1.56-1.97) and 0.30 mm/y (95% CI, 0.28-0.31). For STGD1, using FAF it was 1.0 mm²/y (95% CI, 0.77-1.23) and 0.20 mm/y (95% CI, 0.17-0.23); on OCT, it was 0.80 mm²/y (95% CI, 0.72-0.88). No studies on STGD1 reported the growth rate with other imaging modalities or metrics. Growth rates in GA were faster than in STGD1 (p < .05). A larger baseline area of atrophy was generally associated with faster growth rates.CONCLUSIONSThe RPE atrophy growth rate in GA is faster than in STGD1 but with great variation between studies and imaging modalities. Limited information was available for other macular IRD, suggesting further research is needed.

2024-12-01·Molecular Genetics and Genomics

Genotypic spectrum of ABCA4-associated retinal degenerations in 211 unrelated Mexican patients: identification of 22 novel disease-causing variants

Article

作者: Ordoñez-Labastida, Vianey ; Chacon-Camacho, Oscar F ; Villafuerte-de la Cruz, Rocío ; Xilotl-de Jesús, Nancy ; Calderón-Martínez, Ernesto ; Zenteno, Juan Carlos ; Neria-Gonzalez, M Isabel ; Martinez-Rojas, Augusto

AbstractThe purpose of this study was to analyze and molecularly describe the largest group of patients with ABCA4-associated retinal degeneration in Latin America. Pathogenic variants in ABCA4, a member of the ATP Binding Cassette (ABC) transporters superfamily, is one of the most common causes of inherited visual deficiency in humans. Retinal phenotypes associated with genetic defects in ABCA4 are collectively known as ABCA4-associated retinal degenerations (ABCA4R), a group of recessively inherited disorders associated with a high allelic heterogeneity. While large groups of Caucasian and Asiatic individuals suffering from ABCA4R have been well characterized, molecular information from certain ethnic groups is limited or unavailable, precluding a more realistic knowledge of ABCA4-related mutational profile worldwide. In this study, we describe the molecular findings of a large group of 211 ABCA4R index cases from Mexico. Genotyping was performed using either next generation sequencing (NGS) of a retinal dystrophy genes panel or exome. ABCA4 targeted mutation testing was applied to a subgroup of subjects in whom founder mutations were suspected. A total of 128 different ABCA4 pathogenic variants were identified, including 22 previously unpublished variants. The most common type of genetic variation was single nucleotide substitutions which occurred in 92.7% (408/440 alleles). According to the predicted protein effect, the most frequent variant type was missense, occurring in 83.5% of disease-causing alleles (368/440). Mutations such as p.Ala1773Val are fully demonstrated as a founder effect in native inhabitants of certain regions of Mexico. This study also gives us certain indications of other founder effects that need to be further studied in the near future. This is the largest molecularly characterized ABCA4R Latin American cohort, and our results supports the value of conducting genetic screening in underrepresented populations for a better knowledge of the mutational profile leading to monogenic diseases.

项与 ABCA4 相关的新闻（医药）

2024-10-24

·药智网

大涨150%，RNA编辑疗法爆火

近日，Wave Life Sciences公布了其RNA编辑疗法WVE-006在治疗α-1抗胰蛋白酶缺乏症（AATD）的1b/2a期RestorAATion-2研究的积极机制证明数据。根据新闻稿，WVE-006是首个进入临床开发的RNA编辑疗法，而本次的试验结果是RNA编辑疗法在人体中完成首次机制验证。受此消息影响，Wave公司股价当日大涨74%，与一个月前相比，股价更是上涨超过150%，目前市值超过22亿美元。 01 基因编辑新武器，RNA编辑疗法兴起近年来，基因编辑工具的开发，为纠正致病基因突变创造了机会。其中RNA编辑技术与CRISPR-Cas9技术是两大热门基因编辑手段，旨在对遗传信息进行精确修改，以提供持久的治疗效果。两者区别在于，CRISPR-Cas9技术通过直接剪切DNA链上的特定基因序列，实现对基因的编辑。而RNA编辑技术通过特定的酶或编辑因子，对mRNA上的碱基进行修改，从而影响蛋白质的合成。机制的不同，使RNA编辑技术比CRISPR技术可能更具有优势： RNA编辑技术旨在通过改变RNA的序列来补偿有害突变，从而合成正常蛋白质。与CRISPR技术相比，RNA编辑在mRNA水平进行，不直接改变DNA序列，可以有效避免脱靶效应和伦理问题。 RNA分子的短暂性质意味着通过RNA编辑介入的效果是可逆的，不会改变基因，这为临床应用提供了更多的安全保障。 RNA编辑技术为原本无法治疗的疾病开辟了新的治疗可能性，按编辑方法又可分为单碱基编辑和RNA外显子编辑两种主要类型，目前都已有候选药物进入临床阶段。 02 Wave：单碱基编辑领跑者 Wave Life Sciences成立于2012年，是一家临床阶段的RNA编辑疗法开发公司。文章开头提到的WVE-006是该公司针对α-1抗胰蛋白酶缺乏症（AATD）开发的一种创新的单碱基编辑疗法。 AATD是一种由SERPINA1基因突变引起的遗传性疾病，主要病理特点是突变型AAT蛋白的积累。患者通常表现出进行性肺损伤、肝损伤或两者兼而有之，导致频繁住院和潜在致命的肺部疾病和/或肝脏疾病。 Wave公司开发的WVE-006是一种短的、化学修饰的寡核苷酸（AIMer），可以针对性地引导细胞内的腺苷脱氨酶（ADAR）对特定mRNA上的错配碱基进行精准编辑（A-to-I RNA编辑），进而纠正导致蛋白质功能失调的错误。图1 A-to-I RNA编辑图片来源：参考资料2 由于Pi*ZZ型AATD患者不会产生功能性野生型α-1抗胰蛋白酶（M-AAT）蛋白，因此，如果在患者体内检测到M-AAT蛋白，便可确认突变型Z-AAT的mRNA成功编辑。此外，若患者恢复至50%的M-AAT蛋白水平，将与“MZ”杂合子基因型相符，具有较低的AATD相关肺病和肝病风险。本次公布的数据来自RestorAATion-2研究的首个单剂量队列（200mg），包括两例已经完成了57天治疗的Pi*ZZ AATD患者。结果显示，患者血浆中的野生型M-AAT蛋白在第15天达到平均6.9µM，占总AAT蛋白的60%以上。与基线相比，中性粒细胞弹性蛋白酶抑制的增加与功能性M-AAT的产生一致。平均总AAT蛋白从基线时的不可量化水平增加到第15天的10.8µM，达到了监管部门批准AAT增强疗法的基础水平。此外，早在试验第3天，患者的总AAT和M-AAT蛋白水平即较基线增加，并持续到第57天。安全性方面，WVE-006表现出良好的耐受性和安全性。 RestorAATion-2研究仍正在进行，Wave预计在2025年公布多剂量队列数据。值得一提的是，GSK拥有WVE-006的全球独家许可。在RestorAATion-2研究完成后，开发和商业化工作将转移给GSK。Wave最多有资格获得5.25亿美元的里程碑付款以及净销售额的分级特许权使用费。 03 Ascidian：RNA外显子编辑新锐成立于2020年的Ascidian Therapeutics，开创了另一种RNA编辑方式——RNA外显子编辑。 Ascidian的设计灵感来源一种叫海鞘（Ascidian）的低等海洋生物，为了从幼虫生长到成虫，海鞘通过RNA反式剪接（trans-splicing）和选择性剪接重新设计它们的转录组。 Ascidian公司通过设计含有正确RNA序列的RNA外显子，并与靶标信使RNA前体（pre-mRNA）相互作用，再通过反式剪接（trans-splicing）取代细胞自身所带有的突变外显子，来重写RNA，解决疾病的根本原因。图2 RNA外显子编辑疗法的作用机制图片来源：Ascidian官网与只修改一个RNA碱基的单碱基编辑不同，RNA外显子编辑能够一次性改变RNA分子中成千上万的遗传字母，将导致疾病的RNA序列替换为功能正常的RNA序列。今年1月，Ascidian公司首款RNA外显子编辑疗法ACDN-01的IND申请获得美国FDA的许可，并被授予快速通道资格。该疗法拟用于Stargardt病和其他ABCA4相关视网膜病。 ABCA4基因突变是引发Stargardt病的原因之一，该突变导致进行性视网膜变性和视力丧失，目前尚无任何获批的治疗方案。在研疗法中，基因治疗被寄予厚望。但由于ABCA4基因个体较大，无法通过目前已相对成熟的“AAV”构建体递送整个基因。而且，该基因存在太多的突变点位，分布整个基因的各个段落中，无法通过突变特异性碱基编辑来切实解决每个突变。 Ascidian公司开发外显子编辑RNA疗法正好可以解决这些痛点。据Ascidian公司新闻稿，ACDN-01是首个获美国FDA许可进入临床试验的RNA外显子编辑疗法，并且是首款专门针对Stargardt病遗传起源的临床期治疗方法。除了ACDN-01，Ascidian公司还在开发眼科、神经和神经肌肉疾病，以及其他罕见病的RNA外显子编辑疗法。图3 Ascidian在研管线图片来源：Ascidian官网值得一提的是，今年6月，Ascidian公司宣布与罗氏（Roche）达成一项总额高达约18亿美元的研究合作与许可协议，共同发现和开发针对神经疾病的RNA外显子编辑疗法。MNC的加入，有望进一步加快RNA外显子编辑疗法的开发进程。 04 更多RNA编辑公司浮出水面近年来，基于RNA编辑技术而崛起的生物技术公司越来越多，除了Wave Life Sciences和Ascidian Therapeutics这两家龙头公司，还有AIRNA、Amber Bio、ADARx Pharmaceuticals等国外biotech先后获得数千亿美元，甚至上亿美元融资。在中国，同样有不少公司致力于开发RNA编辑疗法。例如，辉大基因首创了CRISPR/Cas13介导的RNA编辑疗法，其用于治疗新生血管性年龄相关性黄斑变性（nAMD）的RNA编辑疗法HG202已开始评估在人体中的安全性和有效性。CRISPR RNA编辑疗法HG204、迷你型dCas13X-RNA碱基编辑器（mxABE）疗法均获得了美国FDA的孤儿药（ODD）和儿科罕见病药物资格（RPDD）双认定。博雅辑因打造了以基因编辑技术为基础的治疗平台，其中RNA碱基编辑平台体内疗法基于RNA单碱基编辑技术LEAPER™，开发针对包括眼科、神经肌肉病以及其他遗传病、非遗传病等疾病的疗法。时夕生物建立了MIMIC RNA编辑平台，利用内源性腺苷脱氨酶(ADAR)进行精确高效RNA编辑，这一技术能在无需对基因组进行永久修改的情况下对蛋白的序列和功能进行修复和优化。锐正基因聚焦于细胞内包括细胞核内靶点，基于新一代安全、高效、靶向性优异的基因编辑、RNA编辑和递送技术，为先天性遗传疾病和后天获得性疾病患者开发创新药物和治疗方案。结语：基因编辑疗法作为一种创新技术，为多种此前缺乏有效治疗手段的疾病带来了新的治疗思路。而RNA编辑是基因编辑的一个细分领域，具有基因治疗持久性的优点，而没有直接DNA编辑或基因置换相关的风险，在遗传疾病等领域展现出治疗潜力。但目前该类疗法仍处于早期探索阶段，进入临床阶段的管线寥寥无几，疗效和安全性都还需要等待验证。参考资料： 1.https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-first-ever-therapeutic-rna-editing 2.https://academic-oup-com.libproxy1.nus.edu.sg/nar/article/52/17/10068/7734167?login=false 3.Biomax：CRISPR已过时?RNA编辑疗法兴起!!!! 4.《首个体内RNA编辑疗法挺进临床，古老生物带来新启示》，医麦客 5.https://ascidian-tx.com/wp-content/uploads/2024/01/Ascidian-IND-Acceptance-Release_FINAL.1.29.24.pdf 声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 小月石转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

基因疗法信使RNA临床结果

2024-10-18

·药明康德

里程碑！全球首次，RNA编辑疗法获临床概念验证

Wave Life Sciences今天宣布其进行中的临床1b/2a期RestorAATion-2研究获得积极结果。该公司旗下在研RNA编辑候选疗法WVE-006能够成功编辑α-1抗胰蛋白酶缺乏症（AATD）患者的基因，完成临床机制验证。Wave预计将在2025年分享多次给药数据。根据新闻稿，WVE-006是首个进入临床开发的RNA编辑疗法，而今天的试验结果是RNA编辑疗法在人体当中完成首次机制验证。 AATD是一种可影响肺和肝脏功能的遗传疾病，由于缺乏具有正常功能的α-1抗胰蛋白酶（AAT），新生儿可能出现肝炎综合征，成年人则可能出现肝纤维化，甚至发展为肝硬化和肝细胞癌。该疾病的主要病理特点是突变型AAT蛋白的积累，这些突变的蛋白会损害肝脏和肺部。在欧美国家和地区大约有20万名患者在两个SERPINA1等位基因上都有Z突变（即Pi*ZZ纯合子基因型）。目前AATD肺病的唯一治疗选择是通过每周静脉输注以递送AAT蛋白。AATD肝病目前尚无治疗方法，许多患者最终需要接受肝脏移植。此次公布的数据来自RestorAATion-2试验中的首个单剂量组（200毫克），包括前两名Pi*ZZ型AATD患者，从试验开始至第57天的结果。由于Pi*ZZ型AATD患者不会自然产生野生型α-1抗胰蛋白酶（M-AAT）蛋白，因此，若在患者体内检测到M-AAT蛋白，便可确认突变型Z-AAT的mRNA成功编辑。此外，若患者恢复至50%的M-AAT蛋白水平，将与“MZ”杂合子基因型相符，具较低的AATD相关肺病和肝病风险。分析显示，患者血浆中的野生型M-AAT蛋白在第15天达到平均6.9微摩尔，占总AAT蛋白的60%以上。与体内产生功能性M-AAT蛋白的结果一致，患者体内中性粒细胞弹性蛋白酶的抑制与基线相较增加。基线时未能检测到患者体内的AAT蛋白，而在试验第15天时，患者的平均总AAT蛋白水平达到10.8微摩尔，达到了监管机构批准AAT增强疗法的标准。此外，早在试验第3天，患者的总AAT和M-AAT蛋白水平即较基线增加，并持续到第57天。目前，WVE-006展现出良好的耐受性和安全性。在RestorAATion-2试验及健康志愿者参与的RestorAATion-1试验中，所有不良事件均为轻度至中度，且未报告任何严重不良事件。 WVE-006是一款通过PN化学修饰和GalNAc偶联，以皮下注射方式给药的潜在“first-in-class”RNA编辑寡核苷酸疗法，由Wave寡核苷酸化学平台开发。该平台具备将腺嘌呤编辑为肌苷（A至I）的能力（即AIMer）。WVE-006的设计旨在修复SERPINA1等位基因编码mRNA中的单碱基突变，从而恢复血液中的功能性野生型AAT蛋白，同时减少异常Z-AAT蛋白的存在，以潜在治疗AATD相关的肺病和/或肝病。Wave公司在2022年与GSK达成了一项为期四年的研发合作协议，授予GSK WVE-006的全球独家许可。在Wave完成RestorAATion-2研究后，开发和商业化责任将由GSK接手。 Wave还在通过该公司的"edit-verse"平台，针对多个关键医疗需求积极推进一系列RNA编辑疗法。该平台结合了遗传数据集和先进的深度学习模型，以识别和靶向新的RNA编辑靶点。而除了Wave，于2020年成立的Ascidian Therapeutics也专注于RNA编辑疗法的开发。该公司的RNA外显子编辑平台结合了先进计算机生物学与高通量分子生物学筛选技术，可设计出一种创新的RNA分子。该公司进展最快的研发项目是针对Stargardt病和其他ABCA4相关视网膜病的在研疗法ACDN-01，该疗法的IND申请在今年1月获得美国FDA的许可，并被授予快速通道资格。新闻稿指出，ACDN-01是首个获美国FDA许可进入临床试验的RNA外显子编辑疗法，并且是首款专门针对Stargardt病遗传起源的临床期治疗方法。该公司同时在今年6月与罗氏（Roche）达成一项总额高达约18亿美元的研究合作与许可协议，将共同发现和开发针对神经疾病的RNA外显子编辑疗法。此外，AIRNA公司也在今年7月成功完成6000万美元融资。AIRNA通过其RESTORE+平台开发药物，该平台优化寡核苷酸序列、化学和递送，以实现精确、高效和安全的RNA编辑。该公司的首个候选药物是一种潜在“best-in-class”的AATD疗法。而Amber Bio公司则在去年8月走出隐匿模式，并获得超额认购的2600万美元种子轮融资。根据公司官网，Amber Bio的基于人工智能专有平台具潜力对数千个不同突变进行RNA编辑，可以重写长达数千碱基对的RNA片段，扩大治疗疾病的范围。与现有基因编辑疗法每次仅针对单一突变进行治疗不同的是，Amber Bio的候选药物原则上可以靶向同一个基因的几千个突变，因此具治疗因多种突变所引起疾病患者的潜力。同月，ADARx Pharmaceuticals也宣布成功完成超额认购的2亿美元C轮融资。ADARx正在开发一种不受限于治疗模式的RNA靶向平台，包括用于抑制、降解和编辑寡核苷酸的技术平台，以及新型寡核苷酸递送技术。参考资料： [1] Wave Life Sciences Announces First-Ever Therapeutic RNA Editing in Humans Achieved in RestorAATion-2 Trial of WVE-006 in Alpha-1 Antitrypsin Deficiency. Retrieved October 16, 2024 from https://www.globenewswire.com/news-release/2024/10/16/2964053/0/en/Wave-Life-Sciences-Announces-First-Ever-Therapeutic-RNA-Editing-in-Humans-Achieved-in-RestorAATion-2-Trial-of-WVE-006-in-Alpha-1-Antitrypsin-Deficiency.html 内容来源于网络，如有侵权，请联系删除。

信使RNA寡核苷酸临床结果基因疗法

2024-10-14

·GlobeNewswire-Health Care

Belite Bio Announces Presentations at the American Academy of Ophthalmology 2024 Annual Meeting

SAN DIEGO, Oct. 14, 2024 (GLOBE NEWSWIRE) -- Belite Bio, Inc (NASDAQ: BLTE) (“Belite” or the “Company”), a clinical-stage biopharmaceutical drug development company focused on advancing novel therapeutics targeting degenerative retinal diseases that have significant unmet medical needs, today announced that the Company will present data from its completed Phase II adolescent Stargardt disease trial at the American Academy of Ophthalmology Annual Meeting (AAO 2024) being held October 18-21, 2024, in Chicago, IL. Podium Presentation: Title: Tinlarebant (LBS-008) for Adolescents with Stargardt DiseasePresentation Type: Late breaking developments (live broadcast)Presenting Author: Quan Dong Nguyen, MD, MScSession: RET16Date/Time: Saturday, October 19, 2024; 10:33 AM – 10:40 AM CDTLocation: Arie Crown Theater (Lakeside Center building, 1F), Chicago, IL E-poster Presentation Title: Investigation of an Oral Retinol Binding Protein 4 Antagonist in the Treatment of Childhood-onset Stargardt DiseasePresenting Author: Nathan L Mata, PHDDate/Time: On-demand About Tinlarebant (a/k/a LBS-008) Tinlarebant is a novel oral therapy that is intended to reduce the accumulation of vitamin A-based toxins (known as bisretinoids) that cause retinal disease in Stargardt Disease type 1 (STGD1) and also contribute to disease progression in geographic atrophy, or advanced dry age-related macular degeneration (AMD). Bisretinoids are by-products of the visual cycle, which is dependent on the supply of vitamin A (retinol) to the eye. Tinlarebant works by reducing and maintaining levels of serum retinol binding protein 4 (RBP4), the sole carrier protein for retinol transport from the liver to the eye. By modulating the amount of retinol entering the eye, Tinlarebant reduces the formation of bisretinoids. Tinlarebant has been granted Fast Track Designation and Rare Pediatric Disease designation in the U.S., Orphan Drug Designation in the U.S. Europe, and Japan, and Sakigake Designation in Japan for the treatment of STGD1. Stargardt Disease (STGD1) STGD1 is the most common inherited macular dystrophy (causing blurring or loss of central vision) in both adults and children. The disease is caused by mutations in a retina-specific gene (ABCA4), which results in progressive accumulation of bisretinoids leading to retinal cell death and progressive loss of central vision. The fluorescent properties of bisretinoids and the development of retinal imaging systems have helped ophthalmologists identify and monitor disease progression. Currently, there are no FDA approved treatments for STGD1. Importantly, the appearance of bisretinoids, followed by retinal cell death, and progressive loss of vision is also observed in geographic atrophy (GA) patients. Therefore, Belite Bio is evaluating safety and efficacy of Tinlarebant in GA patients in a 2-year Phase 3 study (PHOENIX). About Belite Bio Belite Bio is a clinical-stage biopharmaceutical drug development company focused on advancing novel therapeutics targeting degenerative retinal diseases that have significant unmet medical needs, such as Stargardt Disease type 1 (STGD1) and Geographic Atrophy (GA) in advanced dry age-related macular degeneration (AMD), in addition to specific metabolic diseases. Safety and efficacy of Belite’s lead candidate, Tinlarebant, an oral therapy intended to reduce the accumulation of vitamin A-based toxins in the eye, is currently being evaluated in three late-stage clinical trials. In STGD1, a 2-year, Phase 3 study (DRAGON) and a 2-year, Phase 2/3 study (DRAGON II) in adolescent STGD1 subjects are currently ongoing. In GA, a 2-year, Phase 3 study (PHOENIX) is ongoing. For more information, follow us on Twitter, Instagram, LinkedIn, Facebook or visit us at www.belitebio.com. Forward Looking Statements This press release contains forward-looking statements about future expectations and plans, as well as other statements regarding matters that are not historical facts. These statements include but are not limited to statements regarding the potential implications of clinical data for patients, and Belite Bio’s advancement of, and anticipated preclinical activities, clinical development, regulatory milestones, and commercialization of its product candidates, and any other statements containing the words “expect”, “hope” and similar expressions. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including but not limited to Belite Bio’s ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may not support further development or regulatory approval; the timing to complete relevant clinical trials and/or to receive the interim/final data of such clinical trials; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of Belite Bio’s drug candidates; the potential efficacy of Tinlarebant, as well as those risks more fully discussed in the “Risk Factors” section in Belite Bio’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Belite Bio, and Belite Bio undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. Media and Investor Relations Contact: Jennifer Wu / ir@belitebio.com Julie Fallon / belite@argotpartners.com

临床2期快速通道孤儿药临床3期