ArticleBiochimica et biophysica acta2009
Hepatocyte transplantation (HTx) corrects selected neurometabolic abnormalities in murine intermediate maple syrup urine disease (iMSUD).
Article in Biochimica et biophysica acta, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Clinical perspective on the use of human amniotic epithelial cells to treat congenital metabolic diseases with a focus on maple syrup urine disease.Stem cells translational medicine · 2021Article
- Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders.International journal of molecular sciences · 2020Review
- The history and use of human hepatocytes for the treatment of liver diseases: the first 100 patients.Current protocols in toxicology · 2014Article
- Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders.Human molecular genetics · 2014Review
- Brain-blood amino acid correlates following protein restriction in murine maple syrup urine disease.Orphanet journal of rare diseases · 2014Article
- Therapeutic hepatocyte transplant for inherited metabolic disorders: functional considerations, recent outcomes and future prospects.Journal of inherited metabolic disease · 2014Review
- Non-physiological amino acid (NPAA) therapy targeting brain phenylalanine reduction: pilot studies in PAHENU2 mice.Journal of inherited metabolic disease · 2013Article
- Placental stem cell correction of murine intermediate maple syrup urine disease.Hepatology (Baltimore, Md.) · 2013Article
- Characterization of 2-(methylamino)alkanoic acid capacity to restrict blood-brain phenylalanine transport in Pah enu2 mice: preliminary findings.Molecular genetics and metabolism · 2013Article
- Effect of specific activation of γ-aminobutyric acid receptor in vivo on oxidative stress-induced damage after extended hepatectomy.Hepatology research : the official journal of the Japan Society of Hepatology · 2012Article
- Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease.Disease models & mechanisms · 2012Article
- Advances and challenges in the treatment of branched-chain amino/keto acid metabolic defects.Journal of inherited metabolic disease · 2012Review
- Liver transplantation for classical maple syrup urine disease: long-term follow-up in 37 patients and comparative United Network for Organ Sharing experience.The Journal of pediatrics · 2012Article
- Therapeutic liver repopulation for phenylketonuria.Journal of inherited metabolic disease · 2010Review
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
Skvorak et al. [1] demonstrated the therapeutic efficacy of HTx in a murine model of iMSUD, confirming significant metabolic improvement and survival. To determine the effect of HTx on extrahepatic organs, we examined the metabolic effects of HTx in brain from iMSUD animals. Amino acid analysis revealed that HTx corrected increased ornithine, partially corrected depleted glutamine, and revealed a trend toward alloisoleucine correction. For amino acid and monoamine neurotransmitters, decreased GABA was partially corrected with HTx, while the l-histidine dipeptide of GABA, homocarnosine, was decreased in iMSUD mice and hypercorrected following HTx. Elevated branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in MSUD can deplete brain tyrosine and tryptophan (the precursors of monoamine neurotransmitters, dopamine (DA) and serotonin (5-hydroxytryptamine; 5-HT)) through competition via the large neutral amino acid transporter. HTx corrected decreased DA levels and the DA metabolite, 3-methoxytyramine, and partially corrected the DA intermediate 3,4-dihydroxyphenylacetate (DOPAC) and 5-HT levels, despite normal tyrosine and tryptophan levels in iMSUD mouse brain. We further observed enhanced intracellular turnover of both DA and 5-HT in iMSUD mouse brain, both of which partially corrected with HTx. Our results suggest new pathomechanisms of neurotransmitter metabolism in this disorder and support the therapeutic relevance of HTx in iMSUD mice, while providing proof-of-principle that HTx has corrective potential in extrahepatic organs.
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