ArticleHuman gene therapy2016
Long-Term Restoration of Thymidine Phosphorylase Function and Nucleoside Homeostasis Using Hematopoietic Gene Therapy in a Murine Model of Mitochondrial Neurogastrointestinal Encephalomyopathy.
Article in Human gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Mitochondrial neurogastrointestinal encephalomyopathy in china: a novel TYMP variant and comprehensive clinical-genetic insights.Orphanet journal of rare diseases · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective.Pharmaceutics · 2022Review
- AAV-vector based gene therapy for mitochondrial disease: progress and future perspectives.Orphanet journal of rare diseases · 2022Review
- Stem cell-derived mitochondria transplantation: A promising therapy for mitochondrial encephalomyopathy.CNS neuroscience & therapeutics · 2021Review
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network.Journal of inherited metabolic disease · 2021Review
- Engineering of the Recombinant Expression and PEGylation Efficiency of the Therapeutic Enzyme Human Thymidine Phosphorylase.Frontiers in bioengineering and biotechnology · 2021Article
- Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment.Journal of translational genetics and genomics · 2020Article
- Alpha-1-Antitrypsin Promoter Improves the Efficacy of an Adeno-Associated Virus Vector for the Treatment of Mitochondrial Neurogastrointestinal Encephalomyopathy.Human gene therapy · 2019Article
- Cardiovascular Manifestations of Mitochondrial Disease.Biology · 2019Review
- Safety and Efficacy of Erythrocyte Encapsulated Thymidine Phosphorylase in Mitochondrial Neurogastrointestinal Encephalomyopathy.Journal of clinical medicine · 2019Article
- Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1).Journal of clinical medicine · 2018Review
- Transplantation, gene therapy and intestinal pathology in MNGIE patients and mice.BMC gastroenterology · 2018Article
- Long-Term Sustained Effect of Liver-Targeted Adeno-Associated Virus Gene Therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy.Human gene therapy · 2018Article
- Preclinical Efficacy and Safety Evaluation of Hematopoietic Stem Cell Gene Therapy in a Mouse Model of MNGIE.Molecular therapy. Methods & clinical development · 2018Article
- Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the Fourth Decade, What We Have Learned So Far.Frontiers in genetics · 2018Review
- Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by Thymidine Phosphorylase Enzyme Deficiency: From Pathogenesis to Emerging Therapeutic Options.Frontiers in cellular neuroscience · 2017Review
- Mitochondrial DNA maintenance defects: potential therapeutic strategies.Molecular genetics and metabolismReview
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a metabolic disorder caused by mutations in TYMP, encoding thymidine phosphorylase (TP). In MNGIE patients, TP dysfunction produces systemic thymidine and deoxyuridine accumulation, which ultimately impairs mitochondrial DNA replication and results in mitochondrial dysfunction. To date, only allogeneic hematopoietic stem cell transplantation has demonstrated long-term clinical efficacy, but high morbidity and mortality associated with this procedure necessitate the search for safer alternatives. In a previous study, we demonstrated that hematopoietic stem cell gene therapy using a lentiviral vector containing the coding sequence of TYMP restored the biochemical homeostasis in an animal model of MNGIE. In the present follow-up study, we show that ectopic expression of TP in the hematopoietic system restores normal nucleoside levels in plasma, as well as in tissues affected in MNGIE such as small intestine, skeletal muscle, brain, and liver. Mitochondrial dNTP pool imbalances observed in liver of the animal model were also corrected by the treatment. The biochemical effects were maintained at least 20 months even with low levels of chimerism. No alterations in the blood cell counts or other toxic effects were observed in association with the lentiviral transduction or TP overexpression. These results further support the notion that gene therapy is a feasible treatment option for MNGIE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.