ArticlePloS one2014
Liver as a source for thymidine phosphorylase replacement in mitochondrial neurogastrointestinal encephalomyopathy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Collagen and microvascular alterations contribute to neuromuscular degeneration and disease progression in chronic intestinal pseudo-obstruction.Journal of internal medicine · 2026Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Enteric Neuromyopathies: Highlights on Genetic Mechanisms Underlying Chronic Intestinal Pseudo-Obstruction.Biomolecules · 2022Review
- Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) Disease.Archives of Iranian medicine · 2022Article
- Clinical spectrum of early onset "Mediterranean" (homozygous p.P131L mutation) mitochondrial neurogastrointestinal encephalomyopathy.JIMD reports · 2022Article
- Novel understanding on genetic mechanisms of enteric neuropathies leading to severe gut dysmotility.European journal of histochemistry : EJH · 2021Review
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Moving towards clinical trials for mitochondrial diseases.Journal of inherited metabolic disease · 2021Review
- Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications.Journal of neurology · 2020Article
- Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).Molecular genetics and metabolism · 2020Article
- Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment.Journal of translational genetics and genomics · 2020Article
- Liver background uptake of [American journal of nuclear medicine and molecular imaging · 2020Article
- Article
- Long-Term Sustained Effect of Liver-Targeted Adeno-Associated Virus Gene Therapy for Mitochondrial Neurogastrointestinal Encephalomyopathy.Human gene therapy · 2018Article
- Thymidine phosphorylase: A potential new target for treating cardiovascular disease.Trends in cardiovascular medicine · 2018Review
- Distinct substrate specificity and physicochemical characterization of native human hepatic thymidine phosphorylase.PloS one · 2018Article
- Mitochondrial Neurogastrointestinal Encephalomyopathy: Into the Fourth Decade, What We Have Learned So Far.Frontiers in genetics · 2018Review
- Recent advances in liver transplantation for metabolic disease.Journal of inherited metabolic disease · 2017Review
- Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by Thymidine Phosphorylase Enzyme Deficiency: From Pathogenesis to Emerging Therapeutic Options.Frontiers in cellular neuroscience · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive mitochondrial disease associated with mutations in the nuclear TYMP gene. As a result, the thymidine phosphorylase (TP) enzyme activity is markedly reduced leading to toxic accumulation of thymidine and therefore altered mitochondrial DNA. MNGIE is characterized by severe gastrointestinal dysmotility, neurological impairment, reduced life expectancy and poor quality of life. There are limited therapeutic options for MNGIE. In the attempt to restore TP activity, allogenic hematopoietic stem cell transplantation has been used as cellular source of TP. The results of this approach on ∼ 20 MNGIE patients showed gastrointestinal and neurological improvement, although the 5-year mortality rate is about 70%. In this study we tested whether the liver may serve as an alternative source of TP. We investigated 11 patients (7M; 35-55 years) who underwent hepatic resection for focal disorders. Margins of normal liver tissue were processed to identify, quantify and localize the TP protein by Western Blot, ELISA, and immunohistochemistry, and to evaluate TYMP mRNA expression by qPCR. Western Blot identified TP in liver with a TP/GAPDH ratio of 0.9 ± 0.5. ELISA estimated TP content as 0.5 ± 0.07 ng/μg of total protein. TP was identified in both nuclei and cytoplasm of hepatocytes and sinusoidal lining cells. Finally, TYMP mRNA was expressed in the liver. Overall, our study demonstrates that the liver is an important source of TP. Orthotopic liver transplantation may be considered as a therapeutic alternative for MNGIE patients.
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