Professor Mimoun Azzouz

Neuroscience, School of Medicine and Population Health

Chair of Translational Neuroscience

ERC Advanced Investigator

Director of Gene Therapy Innovation and Manufacturing Centre (GTIMC)

ARDAT Coordinator

m.azzouz@sheffield.ac.uk
+44 114 222 2238

+44 114 222 0654 (Administrator: Laura Haslam)

Room B31, Sheffield Institute for Translational Neuroscience (SITraN)

Full contact details

Professor Mimoun Azzouz
Neuroscience, School of Medicine and Population Health
Room B31
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ

Profile

Professor Azzouz obtained a Master in Neuroscience with 1st Class Honours from the University of Marseille in 1994. In 1997 he was awarded a PhD in Neuropharmacology at the University Louis Pasteur in Strasbourg. He then worked as post-doctoral scientist at the Gene Therapy Center in Lausanne, Switzerland from 1997 to 2000.

He was recruited in 2000 by Oxford BioMedica plc as Senior Scientist then appointed as Director of Neurobiology in 2003. In 2006, he was invited to join the University of Sheffield and was appointed to the Chair of Translational Neuroscience. Azzouz is currently Deputy Head of Department, Research & Innovation.

His track record of translational research productivity is characterised by publications in top ranking scientific journals. He won prestigious awards including the ERC Advanced Investigator (2011) and ERC Proof-of-Concept (2017) Awards. These awards are top level EU ad hominem award acknowledging his pre-eminence in European biomedical research.

He is a member Panels/Boards for various funding bodies such as the Medical Research Council (Translational MRC Panel, UK), the French Muscular Dystrophy Association (AFM), the Health Research Board (HRB) of Ireland, Research Council of Norway, and the Neuroscience Panel, Germany.

He has been recently named as Board member of the British Society for Gene and Cell Therapy. He serves as Scientific Advisor for pharmaceutical companies and other organisations.

Research interests

Professor Azzouz has achieved international pre-eminence in the field of gene therapy applications and vector development for neurodegenerative diseases. His contribution has been outstanding over the last 15 years as evidenced by the quality of publications achieved.

He has achieved a very high international status in an important field. His original and pioneering work, which has already produced major breakthroughs in animal models of neurodegenerative diseases, will in the near future, translate into major therapeutic advances in the field of human neurodegenerative disease.

Azzouz has great drive and passion to employ his scientific skills for the ultimate benefit of patients and families suffering from some of the most devastating diseases in medicine.

Azzouz achievements went beyond therapy development. Indeed, he also made significant discoveries related to the mechanisms of diseases in ALS/MND and SMA. For example, The recent discovery of the mechanism underpinning genome instability and neural cell death caused by C9orf72 expansion in ALS [Nature Neuroscience 20(9):1225-1235. (2017)] and role of PTEN in ALS and SMA [Human Molecular Genetics, 19(16):3159-68 (2010); Brain, 134(Pt 2):506-17 (2011)].

His exceptional achievements were recently recognised at the European level by winning the prestigious ERC Advanced Investigator and ERC PoC Awards designed for individuals with excellence in scientific research. These awards offer him a platform to cement his European leadership in the field of gene therapy and translational neuroscience.

Current projects

Utilisation of viral based gene transfer systems for research and therapy applications.
Design and development of CNS targeted gene therapy vector systems
In vitro and in vivo modelling of ALS/MND and SMA using viral vectors
Identification of novel gene therapeutics to neurodegeneration in motor neuron diseases and HSP.
Development and testing of various gene therapy concepts: neuroprotection (GDNF, VEGF), gene silencing (SOD1), gene replacement (SMN, SPG15, SPG47) and approaches based on CRISPR modulation of expansions (C9orf72).
Clinical development to gene therapeutics: GLP regulatory safety studies and GMP manufacturing
Biology of RNA binding proteins (e.g. SMN, Gle1).
Elucidation of the molecular mechanisms linked to DNA instability in ALS/MND, SMA and Dementia.
Molecular pathways and signalling of motor neuron death (e.g. PTEN)

Collaborations

Professor Pamela Shaw, The University of Sheffield, Sheffield, UK
Professor Michael Sendtner, Germany
Professor Nicola Woodroofe, Sheffield Halam University, Sheffield, UK
Dr Jean-Marc Gallo, King's College London, UK
Dr. Guiseppe Battaglia, The University of Sheffield, UK.
Professor Ruth Luthi-Carter, University of Leicester
Professor Tom Gillingwater, Edinburgh University
Professor Henry Houlden, University College London, UK
Dr Jenny Hirst, University of Cambridge, UK

Publications

Journal articles

Webster CP, Hall B, Crossley OM, Dauletalina D, King M, Lin Y-H, Castelli LM, Yang Z-L, Coldicott I, Kyrgiou-Balli E , Higginbottom A et al (2025) RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD. Life Science Alliance, 8(2), e202402757-e202402757.
Vrellaku B, Sethw Hassan I, Howitt R, Webster CP, Harriss E, McBlane F, Betts C, Schettini J, Lion M, Mindur JE , Duerr M et al (2024) A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders. Molecular Therapy.
Javed H, Menon SA, Al-Mansoori KM, Al-Wandi A, Majbour NK, Ardah MT, Varghese S, Vaikath NN, Haque ME, Azzouz M & El-Agnaf OMA (2024) Retraction Notice to: Corrigendum to “Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson’s Disease and Other Brain Disorders”. Molecular Therapy.
Javed H, Menon SA, Al-Mansoori KM, Al-Wandi A, Majbour NK, Ardah MT, Varghese S, Vaikath NN, Haque ME, Azzouz M & El-Agnaf OMA (2024) Retraction Notice to: Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson’s Disease and Other Brain Disorders. Molecular Therapy.
Castelli LM, Lin Y-H, Sanchez-Martinez A, Gül A, Mohd Imran K, Higginbottom A, Upadhyay SK, Márkus NM, Rua Martins R, Cooper-Knock J , Montmasson C et al (2023) A cell-penetrant peptide blocking C9ORF72 -repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins. Science Translational Medicine, 15(685).
Almaghrabi S, Lovewell T, Azzouz M & Tazi Ahnini R (2023) Characterisation of APS-1 experimental models is crucial for development of novel therapies. BioMed Research International, 2023.
Scarrott JM, Alves-Cruzeiro J, Marchi PM, Webster CP, Yang Z-L, Karyka E, Marroccella R, Coldicott I, Thomas H & Azzouz M (2023) Ap4b1-knockout mouse model of hereditary spastic paraplegia type 47 displays motor dysfunction, aberrant brain morphology and ATG9A mislocalization. Brain Communications, 5(1).
Moll T, Odon V, Harvey C, Collins MO, Peden A, Franklin J, Graves E, Marshall JNG, dos Santos Souza C, Zhang S , Castelli L et al (2023) Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication. Life Science Alliance, 6(1), e202201449-e202201449.
Bauer CS, Webster CP, Shaw AC, Kok JR, Castelli LM, Lin Y-H, Smith EF, Illanes-Álvarez F, Higginbottom A, Shaw PJ , Azzouz M et al (2022) Loss of TMEM106B exacerbates C9ALS/FTD DPR pathology by disrupting autophagosome maturation. Frontiers in Cellular Neuroscience, 16.
Marchi PM, Marrone L, Brasseur L, Coens A, Webster CP, Bousset L, Destro M, Smith EF, Walther CG, Alfred V , Marroccella R et al (2022) C9ORF72-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neurons.. Life Sci Alliance, 5(9).
Han Y, King M, Tikhomirov E, Barasa P, Souza CDS, Lindh J, Baltriukiene D, Ferraiuolo L, Azzouz M, Gullo MR & Kozlova EN (2022) Towards 3D bioprinted spinal cord organoids. International Journal of Molecular Sciences, 23(10). View this article in WRRO
Schmidt NA, Giblin J, MacLachlan TK, Dandapat S, Veres G, Reimer TA, Schulz M, Hatzmann E, Dahy A, LaRosa G , Azzouz M et al (2022) Current global regulatory landscape for biodistribution & shedding assessment of rAAV gene therapies & recommendations of the IMI ARDAT consortium on future directions. Cell and Gene Therapy Insights, 08(03), 377-394.
Karyka E, Berrueta Ramirez N, Webster CP, Marchi PM, Graves EJ, Godena VK, Marrone L, Bhargava A, Ray S, Ning K , Crane H et al (2022) SMN-deficient cells exhibit increased ribosomal DNA damage. Life Science Alliance, 5(8).
Marrone L, Marchi PM, Webster CP, Marroccella R, Coldicott I, Reynolds S, Alves-Cruzeiro J, Yang Z-L, Higginbottom A, Khundadze M , Shaw PJ et al (2022) SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction. Human Molecular Genetics.
Marrone L, Marchi PM & Azzouz M (2022) Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders. Expert Opinion on Biological Therapy.
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Lin Y-H, Myszczynska MA, Heath PR, Livesey MR, Ning K , Azzouz M et al (2021) SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export : genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis. Molecular Neurodegeneration, 16(1). View this article in WRRO
Marchi PM, Marrone L & Azzouz M (2021) Delivery of therapeutic AAV9 vectors via cisterna magna to treat neurological disorders. Trends in Molecular Medicine.
Gatto N, Dos Santos Souza C, Shaw AC, Bell SM, Myszczynska MA, Powers S, Meyer K, Castelli LM, Karyka E, Mortiboys H , Azzouz M et al (2020) Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease. Aging Cell. View this article in WRRO
Crooks L, Cooper-Knock J, Heath PR, Bouhouche A, Elfahime M, Azzouz M, Bakri Y, Adnaoui M, Ibrahimi A, Amzazi S & Tazi-Ahnini R (2020) Identification of single nucleotide variants in the Moroccan population by whole-genome sequencing. BMC Genetics, 21(1).
Franklin JP, Azzouz M & Shaw PJ (2020) SOD1-targeting therapies for neurodegenerative diseases : a review of current findings and future potential. Expert Opinion on Orphan Drugs. View this article in WRRO
Almaghrabi S, Azzouz M & Tazi Ahnini R (2020) AAV9‐mediated AIRE gene delivery clears circulating antibodies and tissue T‐cell infiltration in a mouse model of autoimmune polyglandular syndrome type‐1. Clinical & Translational Immunology, 9. View this article in WRRO
Behne R, Teinert J, Wimmer M, D’Amore A, Davies AK, Scarrott JM, Eberhardt K, Brechmann B, Chen IP-F, Buttermore ED , Barrett L et al (2020) Adaptor protein complex 4 deficiency: a paradigm of childhood-onset hereditary spastic paraplegia caused by defective protein trafficking. Human Molecular Genetics, 29(2), 320-334.
Alves-Cruzeiro J, Webster CP & Azzouz M (2019) The hybrid AAVP tool gets an upgrade. Proceedings of the National Academy of Sciences, 116(37), 18162-18164. View this article in WRRO
Iannitti T, Scarrott J, Likhite S, Coldicott IRP, Lewis KE, Heath PR, Higginbottom A, Myszczynska MA, Milo M, Hautbergue GM , Meyer K et al (2018) Translating SOD1 Gene Silencing toward the Clinic: A Highly Efficacious, Off-Target-free, and Biomarker-Supported Strategy for fALS. Molecular Therapy : Nucleic Acids, 12, 75-88. View this article in WRRO
Lovewell T, McDonagh A, Messenger A, Azzouz M & Tazi-Ahnini R (2018) Meta-analysis of autoimmune regulator-regulated genes in human and murine models: a novel human model provides insights on the role of autoimmune regulator in regulating STAT1 and STAT1-regulated genes. Frontiers in Immunology, 9. View this article in WRRO
Alrafiah A, Karyka E, Coldicott I, Iremonger K, Lewis K, Ning K & Azzouz M (2018) Plastin 3 promotes motor neuron axonal growth and extends survival in a mouse model of spinal muscular atrophy. Molecular Therapy - Methods and Clinical Development, 9, 81-89. View this article in WRRO
Castelli LM, Lin YH, Ferraiuolo L, Sanchez-Martinez A, Ning KE, Azzouz M, Whitworth A, Shaw PJ & Hautbergue GM (2018) SRSF1-dependent nuclear export of C9ORF72 repeat transcripts: targeting toxic gain-of-functions induced by protein sequestration as a selective therapeutic strategy for neuroprotection. Therapeutic Targets for Neurological Diseases, 4. View this article in WRRO
Chandran JS, Sharp PS, Karyka E, Aves-Cruzeiro JMDC, Coldicott I, Castelli L, Hautbergue G, Collins MO & Azzouz M (2017) Site Specific Modification of Adeno-Associated Virus Enables Both Fluorescent Imaging of Viral Particles and Characterization of the Capsid Interactome. Scientific Reports, 7(1). View this article in WRRO
Walker C, Herranz-Martin S, Karyka E, Liao C, Lewis K, Lukashchuk V, Chiang S-C, Ray S, Mulcahy PJ, Jurga M , Tsagakis I et al (2017) C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair. Nature Neuroscience, 20, 1225-1235. View this article in WRRO
Herranz-Martin S, Chandran J, Lewis K, Mulcahy P, Higginbottom A, Walker C, Valenzuela IM-PY, Jones RA, Coldicott I, Iannitti T , Akaaboune M et al (2017) Viral delivery of C9ORF72 hexanucleotide repeat expansions in mice lead to repeat length dependent neuropathology and behavioral deficits.. Disease Models & Mechanisms, 10, 859-868. View this article in WRRO
Hautbergue GM, Castelli LM, Ferraiuolo L, Sanchez-Martinez A, Cooper-Knock J, Higginbottom A, Lin YH, Bauer CS, Dodd JE, myszczynska MA , Alam SM et al (2017) SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nature Communications, 8. View this article in WRRO
Stopford M, Higginbottom A, Hautbergue , Cooper-Knock , Mulcahy , De Vos K, Renton A, Pliner H, Calvo A, Chio A , Traynor B et al (2017) C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. Human Molecular Genetics, 26(6), 1133-1145. View this article in WRRO
Azzouz M (2016) Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy. JCI Insight, 1(11). View this article in WRRO
Seytanoglu A, Alsomali NI, Valori CF, McGown A, Kim HR, Ning K, Ramesh T, Sharrack B, Wood JD & Azzouz M (2016) Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo. Neuroscience, 322, 287-297. View this article in WRRO
(2016) Corrigendum to “Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson's Disease and Other Brain Disorders”. Molecular Therapy, 24(4), 843-843.
Javed H, Menon SA, Al-Mansoori KM, Al-Wandi A, Majbour NK, Ardah MT, Varghese S, Vaikath NN, Haque ME, Azzouz M & El-Agnaf OMA (2016) Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson’s Disease and Other Brain Disorders. Molecular Therapy, 24(4), 746-758.
Lukashchuk V, Lewis KE, Coldicott I, Grierson AJ & Azzouz M (2016) AAV9-mediated central nervous system–targeted gene delivery via cisterna magna route in mice. Molecular Therapy - Methods and Clinical Development, 3. View this article in WRRO
Sharp PS, Shaw K, Boorman L, Harris S, Kennerley A, Azzouz M & Berwick J (2015) Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime. Scientific Reports, 5. View this article in WRRO
Tian X, Nyberg S, S. Sharp P, Madsen J, Daneshpour N, Armes SP, Berwick J, Azzouz M, Shaw P, Abbott NJ & Battaglia G (2015) LRP-1-mediated intracellular antibody delivery to the Central Nervous System. Scientific Reports, 5, 11990-11990. View this article in WRRO
Scarrott JM, Herranz-Martín S, Alrafiah AR, Shaw PJ & Azzouz M (2015) Current developments in gene therapy for amyotrophic lateral sclerosis. Expert Opinion on Biological Therapy, 15(7), 935-947. View this article in WRRO
Little D, Valori CF, Mutsaers CA, Bennett EJ, Wyles M, Sharrack B, Shaw PJ, Gillingwater TH, Azzouz M & Ning K (2015) PTEN Depletion Decreases Disease Severity and Modestly Prolongs Survival in a Mouse Model of Spinal Muscular Atrophy. Molecular Therapy, 23(2), 270-277. View this article in WRRO
Mulcahy PJ, Binny C, Muszynski B, Karyka E & Azzouz M (2015) Adeno-Associated Vectors for Gene Delivery to the Nervous System, 1-22.
Sharp PS, Shaw K, Boorman L, Harris S, Kennerley AJ, Azzouz M & Berwick J (2015) Erratum: Corrigendum: Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime. Scientific Reports, 5(1).
Bennett EJ, Mead RJ, Azzouz M, Shaw PJ & Grierson AJ (2014) Early Detection of Motor Dysfunction in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis (ALS) Using Home Cage Running Wheels. PLoS ONE, 9(9), e107918-e107918. View this article in WRRO
Mulcahy PJ, Iremonger K, Karyka E, Herranz-Martín S, Shum K-T, Tam JKV & Azzouz M (2014) Gene therapy: a promising approach to treating spinal muscular atrophy.. Hum Gene Ther, 25(7), 575-586.
Tam JKV, Karyka E & Azzouz M (2014) Current and investigational treatments for spinal muscular atrophy. Expert Opinion on Orphan Drugs, 2(5), 465-476.
Yang D-J, Wang X-L, Ismail A, Ashman CJ, Valori CF, Wang G, Gao S, Higginbottom A, Ince PG, Azzouz M , Xu J et al (2014) PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons.. Cell Death Dis, 5, e1096. View this article in WRRO
Nanou A, Higginbottom A, Valori CF, Wyles M, Ning K, Shaw P & Azzouz M (2013) Viral delivery of antioxidant genes as a therapeutic strategy in experimental models of amyotrophic lateral sclerosis.. Mol Ther, 21(8), 1486-1496. View this article in WRRO
Azzouz M & Binny C (2013) Microscopy: Progress and prospect. Journal of Microscopy and Ultrastructure, 1(3), 63-63.
Wang L, Chierico L, Little D, Patikarnmonthon N, Yang Z, Azzouz M, Madsen J, Armes SP & Battaglia G (2012) Encapsulation of Biomacromolecules within Polymersomes by Electroporation. Angewandte Chemie, 124(44), 11284-11287.
Wang L, Chierico L, Little D, Patikarnmonthon N, Yang Z, Azzouz M, Madsen J, Armes SP & Battaglia G (2012) Encapsulation of biomacromolecules within polymersomes by electroporation.. Angew Chem Int Ed Engl, 51(44), 11122-11125.
Ismail A, Ning K, Al-Hayani A, Sharrack B & Azzouz M (2012) PTEN: A molecular target for neurodegenerative disorders. TRANSLATIONAL NEUROSCIENCE, 3(2), 132-142.
Ning K, Drepper C, Valori CF, Wyles M, Ismail A, Higginbottom A, Herrmann T, Shaw PJ, Sendtner M & Azzouz M (2011) PTEN signalling in motor neuron disease (ALS & SMA). HUMAN GENE THERAPY, 22(10), A64-A64.
Ismail A, Ning K, Sharrack B & Azzouz M (2011) Impact of PTEN modulation on motor neuron survival in experimental models of motor neuron disease. HUMAN GENE THERAPY, 22(10), A62-A62.
Little D, Ning K, Nanou A, Wang LG, Canton I, Battaglia G & Azzouz M (2011) Polymersome mediated gene therapy for spinal muscular atrophy. HUMAN GENE THERAPY, 22(10), A83-A84.
Azzouz M (2011) Current Advances in Gene Therapy for Spinal Muscular Atrophy. HUMAN GENE THERAPY, 22(10), A19-A19.
Nanou A, Higginbottom A, Wyles M, Ning K, Shaw P & Azzouz M (2011) Gene therapy approaches to evaluate neuroprotection in experimental models of Amyotrophic Lateral Sclerosis. HUMAN GENE THERAPY, 22(10), A64-A64.
Mead RJ, Bennett EJ, Kennerley AJ, Sharp P, Sunyach C, Kasher P, Berwick J, Pettmann B, Battaglia G, Azzouz M , Grierson A et al (2011) Optimised and rapid pre-clinical screening in the SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS).. PLoS One, 6(8), e23244. View this article in WRRO
Kirby J, Ning K, Ferraiuolo L, Heath PR, Ismail A, Kuo S-W, Valori CF, Cox L, Sharrack B, Wharton SB , Ince PG et al (2011) Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis.. Brain, 134(Pt 2), 506-517. View this article in WRRO
Valori CF, Ning K, Wyles M, Mead RJ, Grierson AJ, Shaw PJ & Azzouz M (2010) Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy.. Sci Transl Med, 2(35), 35ra42.
Ning K, Drepper C, Valori CF, Ahsan M, Wyles M, Higginbottom A, Herrmann T, Shaw P, Azzouz M & Sendtner M (2010) PTEN depletion rescues axonal growth defect and improves survival in SMN-deficient motor neurons.. Hum Mol Genet, 19(16), 3159-3168.
Jarraya B, Boulet S, Ralph GS, Jan C, Bonvento G, Azzouz M, Miskin JE, Shin M, Delzescaux T, Drouot X , Hérard A-S et al (2009) Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia.. Sci Transl Med, 1(2), 2ra4.
Nanou A & Azzouz M (2009) Gene therapy for neurodegenerative diseases based on lentiviral vectors.. Prog Brain Res, 175, 187-200.
Valori CF, Ning K, Wyles M & Azzouz M (2008) Development and applications of non-HIV-based lentiviral vectors in neurological disorders.. Curr Gene Ther, 8(6), 406-418.
Azzouz M (2006) Gene Therapy for ALS: progress and prospects.. Biochim Biophys Acta, 1762(11-12), 1122-1127.
Wong L-F, Yip PK, Battaglia A, Grist J, Corcoran J, Maden M, Azzouz M, Kingsman SM, Kingsman AJ, Mazarakis ND & McMahon SB (2006) Retinoic acid receptor beta2 promotes functional regeneration of sensory axons in the spinal cord.. Nat Neurosci, 9(2), 243-250.
Ralph GS, Binley K, Wong L-F, Azzouz M & Mazarakis ND (2006) Gene therapy for neurodegenerative and ocular diseases using lentiviral vectors.. Clin Sci (Lond), 110(1), 37-46.
Teng Q, Garrity-Moses M, Federici T, Tanase D, Liu JK, Mazarakis ND, Azzouz M, Walmsley LE, Carlton E & Boulis NM (2005) Trophic activity of Rabies G protein-pseudotyped equine infectious anemia viral vector mediated IGF-I motor neuron gene transfer in vitro.. Neurobiol Dis, 20(3), 694-700.
Dowd E, Monville C, Torres EM, Wong L-F, Azzouz M, Mazarakis ND & Dunnett SB (2005) Lentivector-mediated delivery of GDNF protects complex motor functions relevant to human Parkinsonism in a rat lesion model.. Eur J Neurosci, 22(10), 2587-2595.
Ralph GS, Mazarakis ND & Azzouz M (2005) Therapeutic gene silencing in neurological disorders, using interfering RNA.. J Mol Med (Berl), 83(6), 413-419.
Ralph GS, Radcliffe PA, Day DM, Carthy JM, Leroux MA, Lee DCP, Wong L-F, Bilsland LG, Greensmith L, Kingsman SM , Mitrophanous KA et al (2005) Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model.. Nat Med, 11(4), 429-433.
Azzouz M, Le T, Ralph GS, Walmsley L, Monani UR, Lee DCP, Wilkes F, Mitrophanous KA, Kingsman SM, Burghes AHM & Mazarakis ND (2004) Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy.. J Clin Invest, 114(12), 1726-1731.
Azzouz M & Mazarakis N (2004) Non-primate EIAV-based lentiviral vectors as gene delivery system for motor neuron diseases.. Curr Gene Ther, 4(3), 277-286.
Azzouz M, Kingsman SM & Mazarakis ND (2004) Lentiviral vectors for treating and modeling human CNS disorders.. J Gene Med, 6(9), 951-962.
Guillot S, Azzouz M, Déglon N, Zurn A & Aebischer P (2004) Local GDNF expression mediated by lentiviral vector protects facial nerve motoneurons but not spinal motoneurons in SOD1(G93A) transgenic mice.. Neurobiol Dis, 16(1), 139-149.
Azzouz M, Ralph GS, Storkebaum E, Walmsley LE, Mitrophanous KA, Kingsman SM, Carmeliet P & Mazarakis ND (2004) VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model.. Nature, 429(6990), 413-417.
Wong LF, Azzouz M, Walmsley LE, Askham Z, Wilkes FJ, Mitrophanous KA, Kingsman SM & Mazarakis ND (2004) Transduction patterns of pseudotyped lentiviral vectors in the nervous system (vol 9, pg 101, 2003). MOL THER, 9(5), 765-765.
Azzouz M, Ralph S, Wong L-F, Day D, Askham Z, Barber RD, Mitrophanous KA, Kingsman SM & Mazarakis ND (2004) Neuroprotection in a rat Parkinson model by GDNF gene therapy using EIAV vector.. Neuroreport, 15(6), 985-990.
Wong L-F, Azzouz M, Walmsley LE, Askham Z, Wilkes FJ, Mitrophanous KA, Kingsman SM & Mazarakis ND (2004) Transduction patterns of pseudotyped lentiviral vectors in the nervous system.. Mol Ther, 9(1), 101-111.
Azzouz M, Martin-Rendon E, Barber RD, Mitrophanous KA, Carter EE, Rohll JB, Kingsman SM, Kingsman AJ & Mazarakis ND (2002) Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson's disease.. J Neurosci, 22(23), 10302-10312.
Martin-Rendon E, Azzouz M & Mazarakis ND (2001) Lentiviral vectors for the treatment of neurodegenerative diseases.. Curr Opin Mol Ther, 3(5), 476-481.
Mazarakis ND, Azzouz M, Rohll JB, Ellard FM, Wilkes FJ, Olsen AL, Carter EE, Barber RD, Baban DF, Kingsman SM , Kingsman AJ et al (2001) Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde axonal transport and access to the nervous system after peripheral delivery.. Hum Mol Genet, 10(19), 2109-2121.
Hottinger AF, Azzouz M, Déglon N, Aebischer P & Zurn AD (2000) Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus.. J Neurosci, 20(15), 5587-5593.
Azzouz M, Hottinger A, Paterna JC, Zurn AD, Aebischer P & Büeler H (2000) Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2.. Hum Mol Genet, 9(5), 803-811.
Azzouz M, Deglon N, Zurn A & Aebischer P (2000) Gene transfer to the mouse spinal cord using a lentiviral vector. EUR J NEUROSCI, 12, 228-228.
Azzouz M, Poindron P, Guettier S, Leclerc N, Andres C, Warter JM & Borg J (2000) Prevention of mutant SOD1 motoneuron degeneration by copper chelators in vitro.. J Neurobiol, 42(1), 49-55.
Azzouz M, Krezel W, Dollé P, Vodouhe C, Warter JM, Poindron P & Borg J (1999) Compensatory mechanism of motor defect in SOD1 transgenic mice by overactivation of striatal cholinergic neurons.. Neuroreport, 10(5), 1013-1018.
Azzouz M, Leclerc N, Gurney M, Warter JM, Poindron P & Borg J (1997) Progressive motor neuron impairment in an animal model of familial amyotrophic lateral sclerosis.. Muscle Nerve, 20(1), 45-51.
Kennel PF, Fonteneau P, Martin E, Schmidt JM, Azzouz M, Borg J, Guenet JL, Schmalbruch H, Warter JM & Poindron P (1996) Electromyographical and motor performance studies in the pmn mouse model of neurodegenerative disease.. Neurobiol Dis, 3(2), 137-147.
Azzouz M, Kenel PF, Warter J-M , Poindron P & Borg J (1996) Enhancement of mouse sciatic nerve regeneration by the long chain fatty alcohol, N-Hexacosanol.. Exp Neurol, 138(2), 189-197.
Borg J, Azzouz M, Leclerc N, Gurney M, Warter JM & Poindron P (1996) Biphasic progression of motor unit dysfunction in an animal model of ALS. J NEUROCHEM, 66, S112-S112.
Wiseman JP, Scarrott JM, Alves-Cruzeiro J, Saffari A, Böger C, Karyka E, Dawes E, Davies AK, Marchi PM, Graves E , Fernandes F et al () Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47. EMBO Molecular Medicine.
Hudák A, Roach M, Pusztai D, Pettkó-Szandtner A, Letoha A, Szilák L, Azzouz M & Letoha T () Syndecan-4 Mediates the Cellular Entry of Adeno-Associated Virus 9. International Journal of Molecular Sciences, 24(4), 3141-3141.
Giovannelli I, Higginbottom A, Kirby J, Azzouz M & Shaw PJ () Prospects for gene replacement therapies in amyotrophic lateral sclerosis. Nature Reviews Neurology.
Winburn I, Schulz M, LaRosa G & Azzouz M () Reply to: Gene therapy to cure haemophilia: Is robust scientific inquiry the missing factor?. Haemophilia.
Cicardi ME, Marrone L, Azzouz M & Trotti D () Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis. The EMBO Journal.
Crooks L, Cooper-Knock J, Heath PR, Bouhouche A, Fahime EE, Azzouz M, Bakri Y, Adnaoui M, Ibrahimi A & Tazi-Ahnini R () Identification of single nucleotide variants in the Moroccan population by whole-genome sequencing.
Lovewell TRJ, McDonagh AJ, Messenger AG, Azzouz M & Tazi-Ahnini R () The AIRE -230Y Polymorphism Affects AIRE Transcriptional Activity: Potential Influence on AIRE Function in the Thymus. PLoS ONE, 10(5). View this article in WRRO
Benson BC, Shaw PJ, Azzouz M, Highley JR & Hautbergue GM () Proteinopathies as Hallmarks of Impaired Gene Expression, Proteostasis and Mitochondrial Function in Amyotrophic Lateral Sclerosis. Frontiers in Neuroscience, 15.

Chapters

Chandran JS, Scarrott JM, Shaw P & Azzouz M (2017) Gene Therapy in the Nervous System: Failures and Successes In El-Khamisy S (Ed.), Personalised Medicine Lessons from Neurodegeneration to Cancer Springer
Chandran JS, Scarrott JM, Shaw PJ & Azzouz M (2017) Gene Therapy in the Nervous System: Failures and Successes, Advances in Experimental Medicine and Biology (pp. 241-257). Springer International Publishing View this article in WRRO

Conference proceedings papers

Roach M, Azzouz M & Webster C (2022) Identification and Validation of Target Receptors for AAV9. MOLECULAR THERAPY, Vol. 30(4) (pp 426-426)
Roach M, Webster C & Azzouz M (2022) Identification and validation of target receptors for AAV9. HUMAN GENE THERAPY, Vol. 33(23-24) (pp A56-A56)
Webster CP, Crossley OM, Yang ZL, Coldicott I, King MC, Souza CDS, Ferraiuolo L & Azzouz M (2022) Gene-based therapeutics for C9ALS/FTD. HUMAN GENE THERAPY, Vol. 33(23-24) (pp A91-A91)
Wiseman J, Cruzeiro J, Scarrott J, Karyka E, Marchi P, Webster CP, Yang Z, Coldicott I, Shaw PJ, Ferraiuolo L & Azzouz M (2022) Gene Replacement Therapy for Spastic Paraplegia 47. HUMAN GENE THERAPY, Vol. 33(23-24) (pp A26-A27)
Alves-Cruzeiro JM, Karyka E, Bauer C, Coldicott I, Simon S, Hautbergue GM, Webster C, Myszczynska M, Higginbottom A, Ferraiuolo L & Azzouz M (2019) Gene editing as a potential therapeutic approach for ALS/FTD-associated with expanded C9ORF72. HUMAN GENE THERAPY, Vol. 30(8) (pp A22-A22)
Iannitti T, Scarrot JM, Coldicott IRP, Kaspar BK, Ferraiuolo L, Shaw PJ & Azzouz M (2016) Gene Therapy for Familial ALS Using AAV9 Mediated Silencing of Mutant SOD1. HUMAN GENE THERAPY, Vol. 27(7) (pp A12-A12) View this article in WRRO
Chandran J, Sharp P, Collins M & Azzouz M (2016) Site specific labelling of adeno-associated virus identifies targets for enhancing viral transduction efficiency. HUMAN GENE THERAPY, Vol. 27(7) (pp A14-A14) View this article in WRRO
Herranz-Martin S, Lewis KE, Coldicott I, Chandran JS, Lukashchuk V, Iannitti T, Shaw PJ & Azzouz M (2016) Experimental modelling of ALS by AAV-mediated in vivo modulation of the C9ORF72 gene. HUMAN GENE THERAPY, Vol. 27(7) (pp A16-A16)
Scarrott J, Ferraiuolo L, Heath P, Gelsthorpe C, Kaspar B, Shaw DP & Azzouz M (2016) Investigating the Specificity of RNAi Molecules in Human Gene Therapy for Superoxide Dismutase 1-linked Familial Amyotrophic Lateral Sclerosis. HUMAN GENE THERAPY, Vol. 27(7) (pp A16-A17)
Alsomali N, Seytanoglu A, Valori C, Kim HR, Ning K, Ramesh T, Sharrack B, Wood JD & Azzouz M (2014) Deficiency in Gle1, an mRNA export mediator, inhibits Schwann cell development in the zebrafish embryo. FEBS JOURNAL, Vol. 281 (pp 771-771)
Almansoori K, Valori C, Furley A, Chandran J, Wood J & Azzouz M (2014) The mRNA exporter GLE1 is essential for embryonic development. FEBS Journal, Vol. 281(Suppl 1) (pp 644-645)
Mohammedeid A, Ning K, Kong SC, Azzouz M & Grierson A (2014) Regulation of protein aggregation by Arfaptin2 in amyotrophic lateral sclerosis. HUMAN GENE THERAPY, Vol. 25(5) (pp A14-A14)
Lovewell TRJ, McDonagh AJ, Messenger AG, Maleki-Dizaji A, Azzouz M & Tazi-Ahnini R (2013) Meta-analysis of AIRE regulated gene expression microarray data reveals a network of transcriptional interactions mediated by intermediate nodes. IMMUNOLOGY, Vol. 140 (pp 58-58)
Woodroofe MN, Sinagra M, Bunning R, Bolton C & Azzouz M (2013) EFFECT OF SILENCING ADAM17 EXPRESSION BY AN ADENOVIRAL VECTOR-MEDIATED RNA INTERFERENCE APPROACH IN CHRONIC RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS.. GLIA, Vol. 61 (pp S43-S43)
Azzouz M (2013) SMN replacement gene therapy for spinal muscular atrophy: clinical development. HUMAN GENE THERAPY, Vol. 24(5) (pp A10-A10)
Little D, Valori C, Wyles M, Shaw P, Azzouz M & Ning K (2013) Systemic delivery of scAAV9 expressing PTEN siRNA prolongs survival in a model of spinal muscular atrophy. HUMAN GENE THERAPY, Vol. 24(5) (pp A27-A27)
Binny C, Karyka E, Ning K, Bennett E, Ince P, Shaw P & Azzouz M (2013) Efficient scAAV9-mediated delivery of SMN to motor neurons in neonatal and juvenile mice. HUMAN GENE THERAPY, Vol. 24(5) (pp A38-A38)
Lovewell TRJ, Mcdonagh AJG, Abu-Duhier F, Azzouz M, Messenger AG & Tazi-Ahnini R (2013) The effect of AIRE-207 polymorphism on AIRE transcriptional activity highlights the potential role of AIRE in the pathogenesis of alopecia areata. JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol. 133(5) (pp 1395-1395)
Valori CF, Ning K, Wyles M, Mead RJ, Grierson AJ, Shaw PJ & Azzouz M (2010) Systemic delivery of scAAV9 expressing SMN prolongs survival in a mouse model of SMA. HUMAN GENE THERAPY, Vol. 21(10) (pp 1424-1425)
Azzouz M, Valori C, Ning K & Wyles M (2010) Current Advances in Gene Therapy for Spinal Muscular Atrophy. HUMAN GENE THERAPY, Vol. 21(10) (pp 1388-1389)
Jarraya B, Lepetit H, Ralph S, Miskin J, Gurruchaga JM, Fenelon G, Boulet S, Jan C, Bonvento G, Azzouz M , Brugiere P et al (2010) Gene Therapy in Parkinson Disease: From Preclinical Studies in Primates to a Phase I Clinical Trial. HUMAN GENE THERAPY, Vol. 21(6) (pp 764-765)
Nanou A, Higginbottom A, Valori C, Wyles M, Ning K, Shaw P & Azzouz M (2010) Oxidative Stress as Target for Neuroprotection in Experimental Models of Amyotrophic Lateral Sclerosis (ALS). NEUROLOGY, Vol. 74(9) (pp A436-A436)
Seytanoglu A, Valori C, Ramesh T, Sharrack B & Azzouz M (2010) Reduced GLE1 Protein Levels Cause Axonal Growth Defects in Zebrafish Motor Neurons. NEUROLOGY, Vol. 74(9) (pp A441-A441)
Ning K, Drepper C, Ismail A, Valori CF, Wyles M, Higginbottom A, Herrmann T, Shaw P, Sharrack B, Sendtner M & Azzouz M (2010) PTEN Depletion Rescues the beta-Actin Deficit in Axonal Growth Cones in Motoneurons from a Mouse Model of Spinal Muscular Atrophy. NEUROLOGY, Vol. 74(9) (pp A489-A489)
Valori C, Ning K, Wyles M & Azzouz M (2010) Complete Rescue of SMA Mouse Model by Systemic Delivery of scAAV9 Mediating SMN Replacement. NEUROLOGY, Vol. 74(9) (pp A287-A287)
Jarraya B, Ralph S, Lepetit H, Stratful E, Boulet S, Jan C, Bonvento G, Azzouz M, Miskin JE, Gurruchaga JM , Vinti M et al (2009) A Phase I/II Trial for Parkinson's Disease Using a Lentiviral Vector (ProSavin (R)). MOLECULAR THERAPY, Vol. 17 (pp S197-S197)
Jarraya B, Ralph S, Lepetit H, Boulet S, Jan C, Bonvento G, Azzouz M, Miskin J, Gurruchaga JM, Palfi S , Fenelon G et al (2008) ProSavin: A gene therapy for Parkinson's Disease. HUMAN GENE THERAPY, Vol. 19(10) (pp 1060-1061)
Goodhead LH, Ning K, Azzouz M, Kingsman SM, Mitrophanous KA & Ralph GS (2008) Optimizing EIAV vectors and delivery routes for ALS gene therapy. HUMAN GENE THERAPY, Vol. 19(4) (pp 405-405)
Jarraya B, Ralph S, Bonvento G, Shin M, Jan C, Delzescaux T, Drouot X, Herard AS, Brouillet E, Azzouz M , Conde F et al (2007) Lentiviral-mediated dopamine replacement mediates sustained correction of parkinsonian symptoms in an MPTP-lesioned NHP model. HUMAN GENE THERAPY, Vol. 18(10) (pp 1026-1026)
Goodhead L, Azzouz M, Kingsman SM, Mitrophanous KA & Ralph S (2007) Optimizing EIAV vectors and delivery routes for ALS gene therapy. HUMAN GENE THERAPY, Vol. 18(10) (pp 1026-1027)
Azzouz M (2006) Treatment of familial ALS using Lentiviral-mediated silencing of mutant SOD1. NEUROMUSCULAR DISORDERS, Vol. 16 (pp S53-S54)
Ralph S, Radcliffe PA, Bilsland L, Greensmith L, Mitrophanous KA, Mazarakis ND & Azzouz M (2004) Targeted ablation of mutant SOD1 in ALS models using lentiviral mediated delivery of interfering RNA. JOURNAL OF NEUROCHEMISTRY, Vol. 90 (pp 59-59)
Tanase D, Teng QS, Krishnaney AA, Liu JK, Garrity-Moses ME, Mazarakis N, Walmsley LE, Azzouz M & Boulis NM (2004) Cervical spinal cord delivery of a lentiviral vector in SOD-1 transgenic mice. MOLECULAR THERAPY, Vol. 9 (pp S201-S201)
Teng QS, Garrity-Moses M, Liu JK, Tanase D, Azzouz M, Walmsley L, Mazarakis ND & Boulis NM (2004) EIAV-IGF-I gene transfer to motor neurons enhances axonal length in vitro. MOLECULAR THERAPY, Vol. 9 (pp S280-S280)
Jarraya B, Azzouz M, Miskin J, Ralph SG, Wilkes F, Rohll J, Walmsley LE, Ellard F, Kingsman SM, Mitrophanous KA , Hantraye P et al (2004) Functional rescue of parkinsonian non-human primates by a dopamine producing multicistronic lentiviral vector. MOLECULAR THERAPY, Vol. 9 (pp S407-S407)
Themis M, Gregory LG, Waddington SN, Holder MV, Mitrophanous KA, Buckley SMK, Bigger BW, Ellard FE, Walmsley LE, Radcliff P , Mazarakis N et al (2004) The fetal approach: A novel therapy for the treatment of musculo-skeletal disease. MOLECULAR THERAPY, Vol. 9 (pp S91-S91)
Azzouz M, Le T, Ralph SG, Wilkes F, Burghes AH, Kingsman SM, Mitrophanous KA & Mazarakis ND (2004) VEGF gene therapy with retrogradely transported lentivirus prolongs survival in mouse ALS model. MOLECULAR THERAPY, Vol. 9 (pp S200-S200)
Azzouz M, Le TN, Waddington S, Walmsley L, Monani U, Wilkes FJ, Themis M, Mitrophanous KA, Burghes A & Mazarakis ND (2003) Lentiviral vector-mediated gene therapy for a mouse model of spinal muscular atrophy. MOLECULAR THERAPY, Vol. 7(5) (pp S248-S248)
Azzouz M, Leclerc N, Gurney M, Warter JM, Poindron P & Borg J (1997) Progressive motor neuron impairment in an animal model of familial amyotrophic lateral sclerosis. NEUROCHEMISTRY (pp 485-490)

Patents

Azzouz M, Scarrott J & Karyka E (2021) Gene Therapy Treatment. WO2021205028A1 Appl. 14 Oct 2021.

Datasets

Gatto N, Souza CDS, Bell S, Shaw A, Myszczynska M, Powers S, Meyer K, Heath P, Castelli L, Karyka E , Mortiboys H et al Directly converted astrocytes retain the ageing features of the donor fibroblasts and elucidate the astrocytic contribution to human CNS health and disease..

Preprints

Moll T, Odon V, Harvey C, Collins MO, Peden A, Franklin J, Graves E, Marshall JNG, Santos Souza CD, Zhang S , Azzouz M et al () Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication, Cold Spring Harbor Laboratory.
Marchi PM, Marrone L, Brasseur L, Bousset L, Webster CP, Destro M, Smith EF, Walther CG, Alfred V, Marroccella R , Robinson D et al () C9orf72-derived poly-GA DPRs undergo endocytic uptake in iNPC-derived astrocytes and spread to motor neurons, Cold Spring Harbor Laboratory.
Castelli LM, Sanchez-Martinez A, Lin Y-H, Upadhyay SK, Higginbottom A, Cooper-Knock J, Gül A, Walton A, Montmasson C, Cohen R , Bauer CS et al () A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration, Cold Spring Harbor Laboratory.
Castelli LM, Cutillo L, Souza CDS, Sanchez-Martinez A, Granata I, Myszczynska MA, Heath PR, Livesey MR, Ning K, Azzouz M , Shaw PJ et al () Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.

Research group

Research team

Evangelia Karyka, Postdoctoral Research Associate
Joseph Scarrott, Postdoctoral Research Associate
Michela Pulix, Postdoctoral Research Associate
Emily Graves, PhD Student
João Alves-Cruzeiro, PhD Student
Paolo Marchi, PhD Student
Louise Whiteley, Research Technician
Nesrin Gariballa, Research Attachment

Professional activities and memberships

2006-08 Advisor for Oxford BioMedica plc
2008-13 Member of the Scientific Advisory Board, Muscular Dystrophy Association (F)
2010 Committee of assessors for Genethon, Paris, France
2010-16 Member of Strategic Board, AFM (F)
2011-12 Advisor for BioMarin Pharmaceutical Inc
2012-14 Panel Member for the Research Council of Norway
2012-16 Panel member for the UK Medical Research Council (DPFS, MRC)
2012-13 Advisor for QBRI, Qatar Foundation, Qatar
2012- Member of Research Excellence Framework 2014 (REF14) Committee, FMDH
2013-14 Neuroscience Panel Member, German Ministry of Education and Research
2013- Panel member, Health Research Board (HRB), Dublin (Ireland)
2014- Wellcome Trust Virtual Panel member for Translational Research Funds
2015-17 Advisor for Spherium biomed
2016- Board member of British Society for Gene & Cell Therapy
2017- Advisory Board, IBRO-MENA
2017- Scientific Advisor for the Batten CLN7 trial (Beat Batten)
2017- Scientific Advisor for CureSPG47
2017- Assessor for Innovate UK
2017- Scientific Advisory Board, Telocyte, USA
2017- Scientific Advisor for Maddi Foundation

Honours and awards

2017: ERC Proof-of-Concept Award
2014: Chair and organiser of Fusion Conference, Cancun, Mexico
2012: ERC Advanced Investigator Award
2012: Nomination for The Shaw Prize 2012
2011: MRC DPFS Award holder
2008: Chairman of UK SMA Conference
2006: Faculty of the American Society of Gene Therapy
2006: Faculty of the American Society of Neuroscience
2006: Approached for an advisory role to the UK Government Department for Environment, Food and Rural Affairs (DEFRA) for “Defra desk study to review environmental risks from research trials and marketing of Genetically Modified (GM) veterinary and human medicines”

School of Medicine and Population Health