Dr Julien Baruteau

Dr Julien Baruteau is a MRC Clinician Scientist Fellow and Group Leader at University College London Great Ormond Street Institute of Child Health, and Consultant in Metabolic Medicine at Great Ormond Street Hospital for Children in London. His research focuses on studying the pathophysiology and developing novel therapies for inherited metabolic diseases. He has developed gene therapy using both viral and non-viral vectors and is the UK chief investigator in first-in-human gene therapy clinical trial. He has expertise in translating academic and industry-led programmes of gene therapies. He is the member of experts’ committees from the European Society of Gene and Cell Therapy, the American Society of Gene and Cell Therapy and the European Society of Human Genetics.

The Baruteau group studies the mechanisms of inherited metabolic diseases and develops dedicated novel therapies for patients affected by these disorders. The main projects are:

Urea Cycle Defects and Arginine Metabolism

The liver-based urea cycle is an essential metabolic pathway, which detoxifies ammonia, an essential neurotoxic compound, produced by the breakdown of proteins. Impaired urea cycle can alter the synthesis of arginine, a substrate for important metabolites such as nitric oxide (NO), creatine and polyamines, are involved in neurotransmission, cellular energy, gene regulation.

We have a long-standing interest in studying argininosuccinic aciduria, the second most common urea cycle disorder caused by deficient argininosuccinate lyase enzyme. We study the clinical phenotype of the disease, the pathophysiology of the disease in different organs using cell and molecular biology and develop novel therapies.

Gene therapy in inherited metabolic diseases

We develop liver and brain targeting gene therapies for inherited metabolic diseases, with both viral (AAV, lentiviral vectors) and non-viral (lipid nanoparticles, exosomes) approaches. Julien Baruteau is the principal investigator in gene therapy clinical trials at Great Ormond Street Hospital for Children. The close links between UCL Great Ormond Street Institute of Child Health and the hospital enable to translate some gene therapy programmes to patients affected by these genetic metabolic diseases.

Developing innovative non-invasive molecular imaging

We explore the pathophysiology of inherited metabolic diseases with novel imaging techniques such as positron emission tomography or specific magnetic resonance imaging sequences. We aim to translate these findings to patients to monitor their disease progression and as efficacy endpoints for novel therapies.

Collaborators

Professor Paul GISSEN, UCL Great Ormond Street Insitute of Child Health
Professor Andrey ABRAMOV, UCL Institute of Neurology, London, UK
Professor Simon WADDINGTON, UCL EGA Institute for Women’s Health, London, UK
Professor Ahad RAHIM, UCL School of Pharmacy
Doctor Gabriele LIGNANI, UCL Institute of Neurology, London, UK
Doctor Tim WITNEY, King’s College University, London, UK
Professor Martin FEELISCH, Southampton University, Southampton, UK
Professor Ian ALEXANDER, Children Medical Research Institute, Westmead, Australia
Professor Nicola BRUNETTI-PIERRI, TIGEM, Naples, Italy
Professor Ayelet EREZ, Weizmann Institute of Science, Rehovot, Israel

Funders

Publications

2024

Duff C, Islam M, Gagliano O, Pramod H, Rashidi H, Kurian MA, Gissen P, Baruteau J.Generation of induced pluripotent stem cells (UCLi024-A) from a patient with argininosuccinate lyase deficiency carrying a homozygous c.437G > A (p.Arg146Gln) mutation. Stem Cell Res. 2024 Apr;76:103365. doi: 10.1016/j.scr.2024.103365. Epub 2024 Feb 28. PubMed PMID: 38422816.
Gurung S, Timmermand OV, Perocheau D, Gil-Martinez AL, Minnion M, Touramanidou L, Fang S, Messina M, Khalil Y, Spiewak J, Barber AR, Edwards RS, Pinto PL, Finn PF, Cavedon A, Siddiqui S, Rice L, Martini PGV, Ridout D, Heywood W, Hargreaves I, Heales S, Mills PB, Waddington SN, Gissen P, Eaton S, Ryten M, Feelisch M, Frassetto A, Witney TH, Baruteau J. mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria. Sci Transl Med. 2024 Jan 10;16(729):eadh1334. doi: 10.1126/scitranslmed.adh1334. Epub 2024 Jan 10. PubMed PMID: 38198573; PubMed Central PMCID: PMC7615535.
Baruteau J, Brunetti-Pierri N, Gissen P. Liver-directed gene therapy for inherited metabolic diseases. J Inherit Metab Dis. 2024 Jan;47(1):9-21. doi: 10.1002/jimd.12709. Epub 2024 Jan 3. Review. PubMed PMID: 38171926.
Duff C, Alexander IE, Baruteau J. Gene therapy for urea cycle defects: An update from historical perspectives to future prospects. J Inherit Metab Dis. 2024 Jan;47(1):50-62. doi: 10.1002/jimd.12609. Epub 2023 Apr 18. Review. PubMed PMID: 37026568; PubMed Central PMCID: PMC10953416.
Bernhardt I, Van Dorp L, Dixon M, McSweeney M, Gan C, Baruteau J, Chakrapani A.Pyruvate carboxylase deficiency type C; variable presentation and beneficial effect of triheptanoin. JIMD Rep. 2024 Jan;65(1):10-16. doi: 10.1002/jmd2.12405. eCollection 2024 Jan. PubMed PMID: 38186850; PubMed Central PMCID: PMC10764197.
Baruteau J, Keshavan N, Venditti CP. Mission possible: Gene therapy for inherited metabolic diseases. J Inherit Metab Dis. 2024 Jan;47(1):5-6. doi: 10.1002/jimd.12708. PubMed PMID: 38221761.

2023

Perocheau D, Gurung S, Touramanidou L, Duff C, Sharma G, Sebire N, Finn PF, Cavedon A, Siddiqui S, Rice L, Martini PGV, Frassetto A, Baruteau J. Ex vivo precision-cut liver slices model disease phenotype and monitor therapeutic response for liver monogenic diseases. F1000Res. 2023;12:1580. doi: 10.12688/f1000research.142014.2. eCollection 2023. PubMed PMID: 38618017; PubMed Central PMCID: PMC11016166
Gurung S, Karamched S, Perocheau D, Seunarine KK, Baldwin T, Alrashidi H, Touramanidou L, Duff C, Elkhateeb N, Stepien KM, Sharma R, Morris A, Hartley T, Crowther L, Grunewald S, Cleary M, Mundy H, Chakrapani A, Batzios S, Davison J, Footitt E, Tuschl K, Lachmann R, Murphy E, Santra S, Uudelepp ML, Yeo M, Finn PF, Cavedon A, Siddiqui S, Rice L, Martini PGV, Frassetto A, Heales S, Mills PB, Gissen P, Clayden JD, Clark CA, Eaton S, Kalber TL, Baruteau J. The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria. J Inherit Metab Dis. 2023 Dec 4;. doi: 10.1002/jimd.12691. [Epub ahead of print] PubMed PMID: 38044746.
Seker Yilmaz B, Baruteau J, Chakrapani A, Champion M, Chronopoulou E, Claridge LC, Daly A, Davies C, Davison J, Dhawan A, Grunewald S, Gupte GL, Heaton N, Lemonde H, McKiernan P, Mills P, Morris AAM, Mundy H, Pierre G, Rajwal S, Sivananthan S, Sreekantam S, Stepien KM, Vara R, Yeo M, Gissen P. Liver transplantation in ornithine transcarbamylase deficiency: A retrospective multicentre cohort study. Mol Genet Metab Rep. 2023 Dec;37:101020. doi: 10.1016/j.ymgmr.2023.101020. eCollection 2023 Dec. PubMed PMID: 38053940; PubMed Central PMCID: PMC10694733.
Cunningham SC, van Dijk EB, Zhu E, Sugden M, Mandwie M, Siew S, Devanapalli B, Tolun AA, Klein A, Wilson L, Aryamanesh N, Gissen P, Baruteau J, Bhattacharya K, Alexander IE. Recapitulation of Skewed X-Inactivation in Female Ornithine Transcarbamylase-Deficient Primary Human Hepatocytes in the FRG Mouse: A Novel System for Developing Epigenetic Therapies. Hum Gene Ther. 2023 Sep;34(17-18):917-926. doi: 10.1089/hum.2023.011. Epub 2023 Sep 11. PubMed PMID: 37350098.
Yeo M, Rehsi P, Dorman M, Grunewald S, Baruteau J, Chakrapani A, Footitt E, Prunty H, McSweeney M. Clinical experience with glycerol phenylbutyrate in 20 patients with urea cycle disorders at a UK paediatric centre. JIMD Rep. 2023 Sep;64(5):317-326. doi: 10.1002/jmd2.12386. eCollection 2023 Sep. PubMed PMID: 37701329; PubMed Central PMCID: PMC10494499.
Touramanidou L, Gurung S, Cosmezcu CA, Perocheau DP, Moulding D, Ridout D, Cavedon A, Siddiqui S, Rice L, Finn PF, Martini PG, Frassetto A, Waddington SN, Counsell JR, Gissen P, Baruteau J. Macrophage inhibitor clodronate enhances liver transduction of lentiviral but not AAV vectors or mRNA lipid nanoparticles in vivo. BioRxiv. 2023 July.
Whitehouse A, Rehsi P, Hartley L, Grunewald S, Yilmaz BS, Pegoretti Baruteau K, Yaman A, Thavagnanam S, Baruteau J. Prolonged respiratory failure responds to conventional therapy in isolated homocysteine remethylation defects. JIMD Rep. 2023 Jul;64(4):274-281. doi: 10.1002/jmd2.12375. eCollection 2023 Jul. PubMed PMID: 37404677; PubMed Central PMCID: PMC10315379.
Elkhateeb N, Olivieri G, Siri B, Boyd S, Stepien KM, Sharma R, Morris AAM, Hartley T, Crowther L, Grunewald S, Cleary M, Mundy H, Chakrapani A, Lachmann R, Murphy E, Santra S, Uudelepp ML, Yeo M, Bernhardt I, Sudakhar S, Chan A, Mills P, Ridout D, Gissen P, Dionisi-Vici C, Baruteau J. Natural history of epilepsy in argininosuccinic aciduria provides new insights into pathophysiology: A retrospective international study.Epilepsia. 2023 Jun;64(6):1612-1626. doi: 10.1111/epi.17596. Epub 2023 Apr 10. PubMed PMID: 36994644.
Westhaus A, Cabanes-Creus M, Dilworth KL, Zhu E, Salas Gómez D, Navarro RG, Amaya AK, Scott S, Kwiatek M, McCorkindale AL, Hayman TE, Frahm S, Perocheau DP, Tran BM, Vincan E, Wong SL, Waters SA, Riddiough GE, Perini MV, Wilson LOW, Baruteau J, Diecke S, González-Aseguinolaza G, Santilli G, Thrasher AJ, Alexander IE, Lisowski L. Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors. Hum Gene Ther. 2023 Apr;34(7-8):273-288. doi: 10.1089/hum.2022.188. PubMed PMID: 36927149; PubMed Central PMCID: PMC10150726.

2022

Seker Yilmaz B, Baruteau J, Arslan N, Aydin HI, Barth M, Bozaci AE, Brassier A, Canda E, Cano A, Chronopoulou E, Connolly GM, Damaj L, Dawson C, Dobbelaere D, Douillard C, Eminoglu FT, Erdol S, Ersoy M, Fang S, Feillet F, Gokcay G, Goksoy E, Gorce M, Inci A, Kadioglu B, Kardas F, Kasapkara CS, Kilic Yildirim G, Kor D, Kose M, Marelli C, Mundy H, O'Sullivan S, Ozturk Hismi B, Ramachandran R, Roubertie A, Sanlilar M, Schiff M, Sreekantam S, Stepien KM, Uzun Unal O, Yildiz Y, Zubarioglu T, Gissen P. Three-Country Snapshot of Ornithine Transcarbamylase Deficiency. Life (Basel). 2022 Oct 27;12(11). doi: 10.3390/life12111721. PubMed PMID: 36362876; PubMed Central PMCID: PMC9695856.
Elangovan R, Baruteau J. Inherited and acquired vitamin B12 deficiencies: Which administration route to choose for supplementation?. Front Pharmacol. 2022;13:972468. doi: 10.3389/fphar.2022.972468. eCollection 2022. Review. PubMed PMID: 36249776; PubMed Central PMCID: PMC9559827.
Duff C, Baruteau J. Modelling urea cycle disorders using iPSCs. NPJ Regen Med. 2022 Sep 26;7(1):56. doi: 10.1038/s41536-022-00252-5. Review. PubMed PMID: 36163209; PubMed Central PMCID: PMC9513077.
Tebani A, Sudrié-Arnaud B, Dabaj I, Torre S, Domitille L, Snanoudj S, Heron B, Levade T, Caillaud C, Vergnaud S, Saugier-Veber P, Coutant S, Dranguet H, Froissart R, Al Khouri M, Alembik Y, Baruteau J, Arnoux JB, Brassier A, Brehin AC, Busa T, Cano A, Chabrol B, Coubes C, Desguerre I, Doco-Fenzy M, Drenou B, Elcioglu NH, Elsayed S, Fouilhoux A, Poirsier C, Goldenberg A, Jouvencel P, Kuster A, Labarthe F, Lazaro L, Pichard S, Rivera S, Roche S, Roggerone S, Roubertie A, Sigaudy S, Spodenkiewicz M, Tardieu M, Vanhulle C, Marret S, Bekri S. Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency. J Med Genet. 2022 Apr;59(4):377-384. doi: 10.1136/jmedgenet-2020-107510. Epub 2021 Mar 18. PubMed PMID: 33737400.
Yeo M, Rehsi P, Dorman M, Grunewald S, Baruteau J, Chakrapani A, Footitt E, Prunty H, McSweeney M. Direct replacement of oral sodium benzoate with glycerol phenylbutyrate in children with urea cycle disorders. JIMD Rep. 2022 Mar;63(2):137-145. doi: 10.1002/jmd2.12274. eCollection 2022 Mar. PubMed PMID: 35281661; PubMed Central PMCID: PMC8898712.

2021

Baruteau J, Cunningham SC, Yilmaz BS, Perocheau DP, Eaglestone S, Burke D, Thrasher AJ, Waddington SN, Lisowski L, Alexander IE, Gissen P. Safety and efficacy of an engineered hepatotropic AAV gene therapy for ornithine transcarbamylase deficiency in cynomolgus monkeys. Mol Ther Methods Clin Dev. 2021 Dec 10;23:135-146. doi: 10.1016/j.omtm.2021.09.005. eCollection 2021 Dec 10. PubMed PMID: 34703837; PubMed Central PMCID: PMC8517016.
van Wegberg AMJ, Trefz F, Gizewska M, Ahmed S, Chabraoui L, Zaki MS, Maillot F, van Spronsen FJ. Undiagnosed Phenylketonuria Can Exist Everywhere: Results From an International Survey. J Pediatr. 2021 Dec;239:231-234.e2. doi: 10.1016/j.jpeds.2021.08.070. Epub 2021 Aug 30. PubMed PMID: 34474089.
Lerner S, Eilam R, Adler L, Baruteau J, Kreiser T, Tsoory M, Brandis A, Mehlman T, Ryten M, Botia JA, Ruiz SG, Garcia AC, Dionisi-Vici C, Ranucci G, Spada M, Mazkereth R, McCarter R, Izem R, Balmat TJ, Richesson R, Gazit E, Nagamani SCS, Erez A. ASL expression in ALDH1A1(+) neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype. Hum Genet. 2021 Oct;140(10):1471-1485. doi: 10.1007/s00439-021-02345-5. Epub 2021 Aug 21. PubMed PMID: 34417872; PubMed Central PMCID: PMC8460544.
Perocheau D, Touramanidou L, Gurung S, Gissen P, Baruteau J. Clinical applications for exosomes: Are we there yet?. Br J Pharmacol. 2021 Jun;178(12):2375-2392. doi: 10.1111/bph.15432. Epub 2021 May 3. Review. PubMed PMID: 33751579; PubMed Central PMCID: PMC8432553.
Ng J, Barral S, De La Fuente Barrigon C, Lignani G, Erdem FA, Wallings R, Privolizzi R, Rossignoli G, Alrashidi H, Heasman S, Meyer E, Ngoh A, Pope S, Karda R, Perocheau D, Baruteau J, Suff N, Antinao Diaz J, Schorge S, Vowles J, Marshall LR, Cowley SA, Sucic S, Freissmuth M, Counsell JR, Wade-Martins R, Heales SJR, Rahim AA, Bencze M, Waddington SN, Kurian MA. Gene therapy restores dopamine transporter expression and ameliorates pathology in iPSC and mouse models of infantile parkinsonism. Sci Transl Med. 2021 May 19;13(594). doi: 10.1126/scitranslmed.aaw1564. PubMed PMID: 34011628; PubMed Central PMCID: PMC7612279.
Gurung S, Perocheau D, Touramanidou L, Baruteau J. The exosome journey: from biogenesis to uptake and intracellular signalling. Cell Commun Signal. 2021 Apr 23;19(1):47. doi: 10.1186/s12964-021-00730-1. Review. PubMed PMID: 33892745; PubMed Central PMCID: PMC8063428.
Massaro G, Geard AF, Liu W, Coombe-Tennant O, Waddington SN, Baruteau J, Gissen P, Rahim AA. Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development. Biomolecules. 2021 Apr 20;11(4). doi: 10.3390/biom11040611. Review. PubMed PMID: 33924076; PubMed Central PMCID: PMC8074255.
Soria LR, Gurung S, De Sabbata G, Perocheau DP, De Angelis A, Bruno G, Polishchuk E, Paris D, Cuomo P, Motta A, Orford M, Khalil Y, Eaton S, Mills PB, Waddington SN, Settembre C, Muro AF, Baruteau J, Brunetti-Pierri N. Beclin-1-mediated activation of autophagy improves proximal and distal urea cycle disorders. EMBO Mol Med. 2021 Feb 5;13(2):e13158. doi: 10.15252/emmm.202013158. Epub 2020 Dec 28. PubMed PMID: 33369168; PubMed Central PMCID: PMC7863400.
Seker Yilmaz B, Davison J, Jones SA, Baruteau J. Novel therapies for mucopolysaccharidosis type III. J Inherit Metab Dis. 2021 Jan;44(1):129-147. doi: 10.1002/jimd.12316. Epub 2020 Sep 28. Review. PubMed PMID: 32944950; PubMed Central PMCID: PMC8436764.

2020

Uggenti C, Lepelley A, Depp M, Badrock AP, Rodero MP, El-Daher MT, Rice GI, Dhir S, Wheeler AP, Dhir A, Albawardi W, Frémond ML, Seabra L, Doig J, Blair N, Martin-Niclos MJ, Della Mina E, Rubio-Roldán A, García-Pérez JL, Sproul D, Rehwinkel J, Hertzog J, Boland-Auge A, Olaso R, Deleuze JF, Baruteau J, Brochard K, Buckley J, Cavallera V, Cereda C, De Waele LMH, Dobbie A, Doummar D, Elmslie F, Koch-Hogrebe M, Kumar R, Lamb K, Livingston JH, Majumdar A, Lorenço CM, Orcesi S, Peudenier S, Rostasy K, Salmon CA, Scott C, Tonduti D, Touati G, Valente M, van der Linden H Jr, Van Esch H, Vermelle M, Webb K, Jackson AP, Reijns MAM, Gilbert N, Crow YJ. cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing. Nat Genet. 2020 Dec;52(12):1364-1372. doi: 10.1038/s41588-020-00737-3. Epub 2020 Nov 23. PubMed PMID: 33230297.
Yilmaz BS, Gurung S, Perocheau D, Counsell J, Baruteau J. Gene therapy for inherited metabolic diseases. J Mother Child. 2020 Nov 10;24(2):53-64. doi: 10.34763/jmotherandchild.20202402si.2004.000009. Review. PubMed PMID: 33554501; PubMed Central PMCID: PMC8518100.