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31 results on '"Prunty, Helen"'

3. Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer

Author

Baruteau, Julien, Perocheau, Dany P., Hanley, Joanna, Lorvellec, Maëlle, Rocha-Ferreira, Eridan, Karda, Rajvinder, Ng, Joanne, Suff, Natalie, Diaz, Juan Antinao, Rahim, Ahad A., Hughes, Michael P., Banushi, Blerida, Prunty, Helen, Hristova, Mariya, Ridout, Deborah A., Virasami, Alex, Heales, Simon, Howe, Stewen J., Buckley, Suzanne M. K., Mills, Philippa B., Gissen, Paul, and Waddington, Simon N.

Published
2018
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8. Lentiviral Hematopoietic Stem Cell Gene Therapy Rescues Clinical Phenotypes in a Murine Model of Pompe Disease

Author

Piras, Giuseppa, primary, Montiel-Equihua, Claudia, additional, Chan, Yee-Ka Agnes, additional, Wantuch, Slawomir, additional, Stuckey, Daniel, additional, Burke, Derek, additional, Prunty, Helen, additional, Phadke, Rahul, additional, Chambers, Darren, additional, Partida-Gaytan, Armando, additional, Leon-Rico, Diego, additional, Panchal, Neelam, additional, Whitmore, Kathryn, additional, Calero, Miguel, additional, Benedetti, Sara, additional, Santilli, Giorgia, additional, Thrasher, Adrian J., additional, and Gaspar, H. Bobby, additional

Published
2020
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11. Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial

Author

Chiesa, Robert, primary, Standing, Joseph F., additional, Winter, Robert, additional, Nademi, Zohreh, additional, Chu, Jan, additional, Pinner, Danielle, additional, Kloprogge, Frank, additional, McLellen, Susan, additional, Amrolia, Persis J., additional, Rao, Kanchan, additional, Lucchini, Giovanna, additional, Silva, Juliana, additional, Ciocarlie, Oana, additional, Lazareva, Arina, additional, Gennery, Andrew R., additional, Doncheva, Bilyana, additional, Cant, Andrew J., additional, Hambleton, Sophie, additional, Flood, Terence, additional, Rogerson, Elizabeth, additional, Devine, Kirsty, additional, Prunty, Helen, additional, Heales, Simon, additional, Veys, Paul, additional, and Slatter, Mary, additional

Published
2019
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13. Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer

Author

Baruteau, Julien, primary, Perocheau, Dany P., additional, Hanley, Joanna, additional, Rocha-Ferreira, Eridan, additional, Karda, Rajvinder, additional, Ng, Joanne, additional, Suff, Nattalie, additional, Rahim, Ahad A., additional, Hughes, Michael P., additional, Banushi, Blerida, additional, Prunty, Helen, additional, Hristova, Mariya, additional, Ridout, Deborah A., additional, Virasami, Alex, additional, Heales, Simon, additional, Howe, Stewen J., additional, Buckley, Suzy M., additional, Mills, Philippa B., additional, Gissen, Paul, additional, and Waddington, Simon N., additional

Published
2018
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16. Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B6-Dependent Epilepsy

Author

Darin, Niklas, primary, Reid, Emma, additional, Prunetti, Laurence, additional, Samuelsson, Lena, additional, Husain, Ralf A., additional, Wilson, Matthew, additional, El Yacoubi, Basma, additional, Footitt, Emma, additional, Chong, W.K., additional, Wilson, Louise C., additional, Prunty, Helen, additional, Pope, Simon, additional, Heales, Simon, additional, Lascelles, Karine, additional, Champion, Mike, additional, Wassmer, Evangeline, additional, Veggiotti, Pierangelo, additional, de Crécy-Lagard, Valérie, additional, Mills, Philippa B., additional, and Clayton, Peter T., additional

Published
2016
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17. Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice

Author

Pai, Yun Jin, Leung, Kit-Yi, Savery, Dawn, Hutchin, Tim, Prunty, Helen, Heales, Simon, Brosnan, Margaret E., Brosnan, John T., Copp, Andrew J., and Greene, Nicholas D.E.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Indoles, Base Sequence, Formates, Genotype, Hyperglycinemia, Nonketotic, Molecular Sequence Data, Glycine, Galactosides, Sequence Analysis, DNA, Glycine Dehydrogenase (Decarboxylating), Real-Time Polymerase Chain Reaction, Immunohistochemistry, Article, Gas Chromatography-Mass Spectrometry, Mice, Folic Acid, Animals, Neural Tube Defects, In Situ Hybridization, DNA Primers
Abstract

Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism., Mutations in the enzyme glycine decarboxylase (GLDC) are associated with neural tube closure defects and non-ketotic hyperglycinemia in humans. Here the authors generate a mouse model with reduced Gldc expression and activity and study the direct effect of the enzyme in these diseases and the mechanisms responsible for neural tube closure defects.

Published
2015

26. Multicentre age-related reference intervals for cerebrospinal fluid serine concentrations: Implications for the diagnosis and follow-up of serine biosynthesis disorders

Author

Moat, Stuart, primary, Carling, Rachel, additional, Nix, Authur, additional, Henderson, Michael, additional, Briddon, Anthony, additional, Prunty, Helen, additional, Talbot, Roy, additional, Powell, Annette, additional, Wright, Katherine, additional, Fuchs, Sabine, additional, and de Koning, Tom, additional

Published
2010
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28. Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre.

Author

Yeo M, Rehsi P, Dorman M, Grunewald S, Baruteau J, Chakrapani A, Footitt E, Prunty H, and McSweeney M

Abstract

In urea cycle disorders (UCDs) ammonia scavenger drugs, usually sodium-based, have been the mainstay of treatment. Increasingly, glycerol phenylbutyrate (GPB, Ravicti®) is being used but scant real-world data exist regarding clinical outcomes. A retrospective study of UCD patients initiated on or switched to GPB was performed at a UK centre. Data on population characteristics, treatment aspects, laboratory measurements, and clinical outcomes were collected before and after patients started GPB with a sub-group analysis undertaken for patients with ≥12 months of data before and after starting GPB. UCDs included arginosuccinate synthetase deficiency ( n  = 8), arginosuccinate lyase deficiency ( n  = 6), ornithine carbamoyltransferase deficiency ( n  = 3), and carbamoyl phosphate synthetase 1 deficiency ( n  = 3). In the sub-group analysis ( n  = 11), GPB resulted in lower plasma ammonia (31 vs. 41 μmol/L, p  = 0.037), glutamine (670 vs. 838 μmol/L, p  = 0.002), annualised hyperammonaemic episodes (0.2 vs. 1.9, p  = 0.020), hospitalisations (0.5 vs. 2.2, p  = 0.010), and hyperammonaemic episodes resulting in hospitalisation (0.2 vs. 1.6, p  = 0.035) reflecting changes seen in the whole group. Overall, patients exposed to sodium and propylene glycol levels above UK daily limits reduced by 78% and 83% respectively. Mean levels of branched chain amino acids, haemoglobin, and white cell count were unchanged. Two adverse drug reactions (pancytopenia, fatigue/appetite loss) resolved without GPB discontinuation. Patients/families preferred GPB for its lower volume, greater palatability and easier administration. GPB appeared to improve biochemical measures and clinical outcomes. The causes are multi-factorial and are likely to include prolonged action of GPB and its good tolerability, even at higher doses, facilitating tighter control of ammonia., Competing Interests: Mildrid Yeo and Melanie McSweeney have received speaker honorarium from Immedica. The remaining authors declare no conflicts of interest., (© 2023 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Published
2023
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29. Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial.

Author

Chiesa R, Standing JF, Winter R, Nademi Z, Chu J, Pinner D, Kloprogge F, McLellen S, Amrolia PJ, Rao K, Lucchini G, Silva J, Ciocarlie O, Lazareva A, Gennery AR, Doncheva B, Cant AJ, Hambleton S, Flood T, Rogerson E, Devine K, Prunty H, Heales S, Veys P, and Slatter M

Subjects
Adolescent, Busulfan administration & dosage, Busulfan adverse effects, Busulfan pharmacokinetics, Child, Child, Preschool, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Monitoring, England, Female, Humans, Infant, Infant, Newborn, Infusions, Intravenous, Male, Models, Biological, Myeloablative Agonists administration & dosage, Myeloablative Agonists adverse effects, Prospective Studies, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Busulfan analogs & derivatives, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Myeloablative Agonists pharmacokinetics, Transplantation Conditioning adverse effects
Abstract

Treosulfan is given off-label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients (n = 87) receiving treosulfan-fludarabine conditioning were followed for at least 1 year posttransplant. PKs were described with a two-compartment model. During follow-up, 11 of 87 patients died and 12 of 87 patients had low engraftment (≤ 20% myeloid chimerism). For each increase in treosulfan area under the curve from zero to infinity (AUC (0-∞) ) of 1,000 mg hour/L the hazard ratio (95% confidence interval) for mortality increase was 1.46 (1.23-1.74), and the hazard ratio for low engraftment was 0.61 (0.36-1.04). A cumulative AUC (0-∞) of 4,800 mg hour/L maximized the probability of success (> 20% engraftment and no mortality) at 82%. Probability of success with AUC (0-∞) between 80% and 125% of this target were 78% and 79%. Measuring PK at the first dose and individualizing the third dose may be required in nonmalignant disease., (© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Published
2020
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30. Lentiviral Hematopoietic Stem Cell Gene Therapy Rescues Clinical Phenotypes in a Murine Model of Pompe Disease.

Author

Piras G, Montiel-Equihua C, Chan YA, Wantuch S, Stuckey D, Burke D, Prunty H, Phadke R, Chambers D, Partida-Gaytan A, Leon-Rico D, Panchal N, Whitmore K, Calero M, Benedetti S, Santilli G, Thrasher AJ, and Gaspar HB

Abstract

Pompe disease is a lysosomal storage disorder caused by malfunctions of the acid alpha-glucosidase (GAA) enzyme with a consequent toxic accumulation of glycogen in cells. Muscle wasting and hypertrophic cardiomyopathy are the most common clinical signs that can lead to cardiac and respiratory failure within the first year of age in the more severe infantile forms. Currently available treatments have significant limitations and are not curative, highlighting a need for the development of alternative therapies. In this study, we investigated the use of a clinically relevant lentiviral vector to deliver systemically GAA through genetic modification of hematopoietic stem and progenitor cells (HSPCs). The overexpression of GAA in human HSPCs did not exert any toxic effect on this cell population, which conserved its stem cell capacity in xenograft experiments. In a murine model of Pompe disease treated at young age, we observed phenotypic correction of heart and muscle function with a significant reduction of glycogen accumulation in tissues after 6 months of treatment. These findings suggest that lentiviral-mediated HSPC gene therapy can be a safe alternative therapy for Pompe disease., (© 2020 The Authors.)

Published
2020
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31. Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B 6 -Dependent Epilepsy.

Author

Darin N, Reid E, Prunetti L, Samuelsson L, Husain RA, Wilson M, El Yacoubi B, Footitt E, Chong WK, Wilson LC, Prunty H, Pope S, Heales S, Lascelles K, Champion M, Wassmer E, Veggiotti P, de Crécy-Lagard V, Mills PB, and Clayton PT

Subjects
Adolescent, Carnosine analogs & derivatives, Carnosine metabolism, Cells, Cultured, Child, Child, Preschool, Exome genetics, Female, Fibroblasts, Homozygote, Humans, Infant, Male, Pedigree, Proline metabolism, Vitamin B 6 blood, Epilepsy genetics, Epilepsy metabolism, Homeostasis genetics, Mutation, Proteins genetics, Pyridoxal Phosphate metabolism, Vitamin B 6 metabolism
Abstract

Pyridoxal 5'-phosphate (PLP), the active form of vitamin B 6 , functions as a cofactor in humans for more than 140 enzymes, many of which are involved in neurotransmitter synthesis and degradation. A deficiency of PLP can present, therefore, as seizures and other symptoms that are treatable with PLP and/or pyridoxine. Deficiency of PLP in the brain can be caused by inborn errors affecting B 6 vitamer metabolism or by inactivation of PLP, which can occur when compounds accumulate as a result of inborn errors of other pathways or when small molecules are ingested. Whole-exome sequencing of two children from a consanguineous family with pyridoxine-dependent epilepsy revealed a homozygous nonsense mutation in proline synthetase co-transcribed homolog (bacterial), PROSC, which encodes a PLP-binding protein of hitherto unknown function. Subsequent sequencing of 29 unrelated indivduals with pyridoxine-responsive epilepsy identified four additional children with biallelic PROSC mutations. Pre-treatment cerebrospinal fluid samples showed low PLP concentrations and evidence of reduced activity of PLP-dependent enzymes. However, cultured fibroblasts showed excessive PLP accumulation. An E.coli mutant lacking the PROSC homolog (ΔYggS) is pyridoxine sensitive; complementation with human PROSC restored growth whereas hPROSC encoding p.Leu175Pro, p.Arg241Gln, and p.Ser78Ter did not. PLP, a highly reactive aldehyde, poses a problem for cells, which is how to supply enough PLP for apoenzymes while maintaining free PLP concentrations low enough to avoid unwanted reactions with other important cellular nucleophiles. Although the mechanism involved is not fully understood, our studies suggest that PROSC is involved in intracellular homeostatic regulation of PLP, supplying this cofactor to apoenzymes while minimizing any toxic side reactions., (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2016
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