MICA: Clinical development of erythrocyte encapsulated thymidine phosphorylase - a therapy for mitochondrial neurogastrointestinal encephalomyopathy

MICA:红细胞包裹胸苷磷酸化酶的临床开发——线粒体神经胃肠道脑肌病的治疗

基本信息

  • 批准号:
    MR/K025406/1
  • 负责人:
  • 金额:
    $ 401.65万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2014
  • 资助国家:
    英国
  • 起止时间:
    2014 至 无数据
  • 项目状态:
    已结题

项目摘要

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)) is an almost invariably fatal inherited metabolic disorder caused by a defect in the gene coding for the enzyme thymidine phosphorylase, resulting in affected individuals producing little or no active enzyme. Thymidine phosphorylase is required for the normal metabolism of the metabolites thymidine and deoxyuridine and in its absence these metabolites accumulate in the body causing damage to the mitochondria, the powerhouse of the cell. Energy dependent tissues such as skeletal muscle and nervous system are therefore adversely affected, manifesting clinically as gastrointestinal dysmotility (for example, vomiting and anorexia), neuropathy (nerve damage leading to, for example, loss of sensation and abnormal eye movements) and severe muscle weakness. MNGIE is relentlessly progressive with patients dying at an average reported age of 37.6 years. Matched bone marrow transplants offer a potential cure but are limited by the availability of a matched donor, carry significant risks of serious complications and have a reported mortality as high as 50%. Currently they are not recommended for those patients who have advanced disease. The research team at St. George's, University of London are world leaders in developing the red blood cell (erythrocyte) as a vehicle for carrying (i.e. encapsulating) therapeutic proteins in the blood. In the current study they are investigating the effectiveness of using the patient's own red blood cells to carry the missing thymidine phosphorylase in the circulation. The red blood cells provide a protected environment in which the enzyme can function. The encapsulated enzyme reduces the levels of toxic metabolites in the blood, thus relieving the nervous system and muscle of their damaging effects. Data obtained from the compassionate use of erythrocyte encapsulated thymidine phosphorylase (EE-TP) in two patients with MNGIE shows that a reduction in plasma thymidine and deoxyuridine concentrations can be causally linked to clinical benefit. The aim of this project is to confirm the safety and clinical effectiveness of EE-TP in a European-wide clinical study in ten patients with MNGIE. Successful results from this study will support applications to the regulatory authorities for a marketing license for EE-TP and ensuring patients globally have equitable access.
线粒体神经胃肠脑肌病(MNGIE)是一种几乎总是致命的遗传性代谢紊乱,由编码胸苷磷酸化酶的基因缺陷引起,导致受影响的个体产生很少或没有活性酶。胸苷磷酸化酶是代谢物胸苷和脱氧尿苷的正常代谢所必需的,并且在其缺乏的情况下,这些代谢物在体内积累,导致对细胞的动力室线粒体的损伤。因此,能量依赖性组织如骨骼肌和神经系统受到不利影响,在临床上表现为胃肠动力障碍(例如呕吐和厌食)、神经病(导致例如感觉丧失和异常眼球运动的神经损伤)和严重肌无力。MNGIE是无情的进步与患者死亡的平均报告年龄为37.6岁。匹配的骨髓移植提供了一种潜在的治愈方法,但受到匹配供体可用性的限制,具有严重并发症的显著风险,并且据报道死亡率高达50%。目前,不推荐用于晚期疾病患者。伦敦大学圣乔治的研究小组是开发红细胞(红细胞)作为血液中携带(即封装)治疗蛋白质的载体的世界领导者。在目前的研究中,他们正在研究使用患者自身的红细胞携带循环中缺失的胸苷磷酸化酶的有效性。红细胞提供了一个受保护的环境,酶可以在其中发挥作用。包封的酶降低血液中有毒代谢物的水平,从而减轻神经系统和肌肉的破坏作用。在2例MNGIE患者中同情使用红细胞包裹胸苷磷酸化酶(EE-TP)获得的数据显示,血浆胸苷和脱氧尿苷浓度的降低与临床获益存在因果关系。本项目的目的是在10名MNGIE患者中进行的欧洲范围的临床研究中确认EE-TP的安全性和临床有效性。本研究的成功结果将支持向监管机构申请EE-TP的上市许可,并确保全球患者享有公平的使用权。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Drug-loaded erythrocytes: on the road toward marketing approval.
载有药物的红细胞:在营销批准的道路上。
Editorial: Biomarkers to evaluate rare diseases
社论:评估罕见疾病的生物标志物
Prime Archives in Genetics
遗传学主要档案
  • DOI:
    10.37247/pag.1.2020.3
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Bax B
  • 通讯作者:
    Bax B
Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment.
Drug Development for Rare Diseases: Challenges and Regulatory Initiatives.
罕见疾病药物开发:挑战和监管举措。
  • DOI:
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Bax BE
  • 通讯作者:
    Bax BE
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Bridget Bax其他文献

Ca<sup>2+</sup> channels in human term trophoblast cells <em>in vitro</em>. A study using the Ca<sup>2+</sup>-sensitive dye fura 2
  • DOI:
    10.1016/s0143-4004(05)80374-1
  • 发表时间:
    1994-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Christopher Bax;Bridget Bax;Murray Bain;Mone Zaidi
  • 通讯作者:
    Mone Zaidi

Bridget Bax的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Bridget Bax', 18)}}的其他基金

Pre-clinical safety studies of erythrocyte encapsulated thymidine phosphorylase
红细胞封装胸苷磷酸化酶的临床前安全性研究
  • 批准号:
    G0902179/1
  • 财政年份:
    2010
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Research Grant

相似国自然基金

Molecular Interaction Reconstruction of Rheumatoid Arthritis Therapies Using Clinical Data
  • 批准号:
    31070748
  • 批准年份:
    2010
  • 资助金额:
    34.0 万元
  • 项目类别:
    面上项目

相似海外基金

Optimal utility-based design of oncology clinical development programmes
基于效用的肿瘤学临床开发项目的优化设计
  • 批准号:
    2734768
  • 财政年份:
    2026
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Studentship
Presymptom: development of a novel machine-learning-derived diagnostic test to rule out infection to enable enhanced clinical care and better targeted anti-microbial use
症状前:开发一种新型的机器学习诊断测试来排除感染,从而加强临床护理和更有针对性的抗菌药物使用
  • 批准号:
    10089281
  • 财政年份:
    2024
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Investment Accelerator
Novel 'extended labour induction' balloon to improve safety of labour induction: Prototype development and preliminary clinical study
新型“延长引产”球囊可提高引产安全性:原型开发和初步临床研究
  • 批准号:
    MR/Y503423/1
  • 财政年份:
    2024
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Research Grant
National Career Development Program for Researchers in Pediatric Clinical Pharmacology
儿科临床药理学研究人员国家职业发展计划
  • 批准号:
    11001312
  • 财政年份:
    2024
  • 资助金额:
    $ 401.65万
  • 项目类别:
Measurement and analysis of radiotherapy small field dosimetry data to support the development of a simulation training product for clinical Radiotherapy Physicists.
放射治疗小场剂量测定数据的测量和分析,以支持临床放射治疗物理学家模拟培训产品的开发。
  • 批准号:
    10089179
  • 财政年份:
    2024
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Collaborative R&D
Development of a Clinical Gait Analysis Service
临床步态分析服务的开发
  • 批准号:
    486987
  • 财政年份:
    2023
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Miscellaneous Programs
RareKids-CAN: Pediatric Rare Disease Clinical Trials and Treatment Network
RareKids-CAN:儿科罕见病临床试验和治疗网络
  • 批准号:
    495575
  • 财政年份:
    2023
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Operating Grants
Development of medical Tc drugs using Tc isotopes and development of a medical gamma-ray camera for clinical applications
利用Tc同位素开发医用Tc药物以及开发用于临床应用的医用伽马射线相机
  • 批准号:
    23H03661
  • 财政年份:
    2023
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development and clinical application of AI model to support diagnosis of dementia using medical big data from electronic medical records
利用电子病历中的医疗大数据支持痴呆症诊断的人工智能模型的开发和临床应用
  • 批准号:
    22KJ3211
  • 财政年份:
    2023
  • 资助金额:
    $ 401.65万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Reducing stigmatizing attitudes and behaviors of nursing students in simulated clinical visits of patients living with HIV in Iran
在伊朗艾滋病毒感染者的模拟临床就诊中减少护生的污名化态度和行为
  • 批准号:
    10542953
  • 财政年份:
    2023
  • 资助金额:
    $ 401.65万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了