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Dr Julien BARUTEAU
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
- UCL Technology Fund
- National Institute for Health Research
- Medical Research Council
- London Advanced Therapy Network
- Innovate UK
- GOSH Charity
- Action Medical Research
- Nutricia
- Moderna
- Evox Therapeutics
Publications
2023
Gurung, Timmermand, Perocheau, Gil-Martinez, Minnion, Touramanidou, Fang, Messina, KhalilY, Barber, Edwards, Finn, Cavedon, Siddiqui, Rice, Martini, Mills, Waddington, Gissen, Eaton, Ryten, Feelisch, Frassetto, Witney, Baruteau mRNA therapy corrects glutathione metabolism and restores ureagenesis in argininosuccinic aciduria. (2023) Sci Transl Med, In Press. BioRxiv preprint: https://www.biorxiv.org/content/10.1101/2022.10.19.512931v1
Gurung, Timmermand, Perocheau, Gil-Martinez, Minnion, Touramanidou, Fang, Messina, KhalilY, Barber, Edwards, Finn, Cavedon, Siddiqui, Rice, Martini, Mills, Waddington, Gissen, Eaton, Ryten, Feelisch, Frassetto, Witney, Baruteau The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria. (2023) J Inherit Metab Dis, In Press. BioRxiv preprint: https://www.biorxiv.org/content/10.1101/2023.10.10.561631v1
Perocheau, Gurung, Touramanidou, Duff, Sharma, Sebire, Finn, Cavedon, Siddiqui, Rice, Martini, Frassetto, Baruteau. Ex vivo precision-cut liver slices model disease phenotype and monitor therapeutic response for liver monogenic diseases. (2023) F1000 Research, in press. BioRxiv preprint: https://www.biorxiv.org/content/10.1101/2023.03.23.533840v1
Touramanidou, Gurung, Cozmescu Perocheau, Moulding, Ridout, Cavedon, Siddiqui, Rice, Finn, Martini, Frassetto, Waddington, Counsell, Gissen, Baruteau. Macrophage inhibitor clodronate enhances liver transduction of lentiviral but not AAV vectors or mRNA lipid nanoparticles in vivo. (2023) BioRxiv preprint: https://www.biorxiv.org/content/10.1101/2023.07.26.550697v1
Yeo M, Rehsi P, Dorman M, Grunewald S, Baruteau J, Chakrapani A, Footitt E, Prunty H, McSweeney M. JIMD Rep. 2023 Jul 23;64(5):317-326. doi: 10.1002/jmd2.12386. eCollection 2023 Sep.PMID: 37701329
Whitehouse A, Rehsi P, Hartley L, Grunewald S, Yilmaz BS, Pegoretti Baruteau K, Yaman A, Thavagnanam S, Baruteau J. JIMD Rep. (2023) Jun 16;64(4):274-281. doi: 10.1002/jmd2.12375. eCollection 2023 Jul. PMID: 37404677
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. Hum Gene Ther. (2023) Sep;34(17-18):917-926. doi: 10.1089/hum.2023.011.
Duff C, Alexander IE, Baruteau J. J Inherit Metab Dis. 2023 Apr 7. doi: 10.1002/jimd.12609.
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.. Epilepsia. (2023) Jun;64(6):1612-1626. doi: 10.1111/epi.17596.
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. Hum Gene Ther. (2023) Apr;34(7-8):273-288. doi: 10.1089/hum.2022.188.PMID: 36927149
2022
Elangovan R, Baruteau J. Inherited and acquired vitamin B12 deficiencies: which administration route to choose for supplementation? Frontiers in Pharmacol. 2022;13:972458.
Duff C, Baruteau J. Modelling urea cycle disorders using iPSCs. NPG Regen Med. 2022;7:56.
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;63(2):137-145.
