Publications
131 results found
Browne E, James R, Schalks R, et al., 2015, Chronic lymphotoxin-alpha expression in the meninges produces sub-pial cortical pathology in the rat, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 135-136, ISSN: 1352-4585
James RE, Browne E, Mazarakis N, et al., 2015, Chronic meningeal production of TNF and interferon-γ can drive cortical grey matter pathology, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 430-430, ISSN: 1352-4585
Eleftheriadou I, Mazarakis N, 2015, Lentiviral vectors for gene delivery to the nervous system, Gene Delivery and Therapy for Neurological Disorders, Editors: Bo, Verhaagen, Publisher: Humana Press, Pages: 23-66, ISBN: 9781493923052
This volume aims to explore the latest developments in adeno-associated viral and lentiviral vectors as well as the gene therapy strategies for the most common neurological disorders, followed by chapters that include step-by-step guides to ...
Pazarentzos E, Mazarakis ND, 2014, Anticancer Gene Transfer for Cancer Gene Therapy, Anticancer Genes, Editors: Grimm, Publisher: Springer, Pages: 255-280, ISBN: 978-1-4471-6457-9
Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field.
Pazarentzos E, Mahul-Mellier A-L, Datler C, et al., 2014, I kappa B alpha inhibits apoptosis at the outer mitochondrial membrane independently of NF-kappa B retention, The EMBO Journal, Vol: 33, Pages: 2814-2828, ISSN: 0261-4189
IκBα resides in the cytosol where it retains the inducible transcription factor NF‐κB. We show that IκBα also localises to the outer mitochondrial membrane (OMM) to inhibit apoptosis. This effect is especially pronounced in tumour cells with constitutively active NF‐κB that accumulate high amounts of mitochondrial IκBα as a NF‐κB target gene. 3T3 IκBα−/− cells also become protected from apoptosis when IκBα is specifically reconstituted at the OMM. Using various IκBα mutants, we demonstrate that apoptosis inhibition and NF‐κB inhibition can be functionally and structurally separated. At mitochondria, IκBα stabilises the complex of VDAC1 and hexokinase II (HKII), thereby preventing Bax recruitment to VDAC1 and the release of cytochrome c for apoptosis induction. When IκBα is reduced in tumour cells with constitutively active NF‐κB, they show an enhanced response to anticancer treatment in an in vivo xenograft tumour model. Our results reveal the unexpected activity of IκBα in guarding the integrity of the OMM against apoptosis induction and open possibilities for more specific interference in tumours with deregulated NF‐κB.
Eleftheriadou I, Manolaras I, Trabalza A, et al., 2014, Presynaptic NMJ aCAR-targeted Lentiviral Vector for Neuroprotective Gene Therapy in ALS, ESGCT and NVGCT Collaborative Congress, Publisher: MARY ANN LIEBERT, INC, Pages: A82-A83, ISSN: 1043-0342
Eleftheriadou I, Trabalza A, Ellison SM, et al., 2014, Specific Retrograde Transduction of Spinal Motor Neurons using Lentiviral Vectors Targeted to Presynaptic NMJ Receptors, MOLECULAR THERAPY, Vol: 22, Pages: 1285-1298, ISSN: 1525-0016
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- Citations: 16
Pazarentzos E, Mazarakis ND, 2014, Anticancer Gene Transfer for Cancer Gene Therapy, ANTICANCER GENES, Vol: 818, Pages: 255-280, ISSN: 0065-2598
Hislop JN, Islam TA, Eleftheriadou I, et al., 2014, Rabies Virus Envelope Glycoprotein Targets Lentiviral Vectors to the Axonal Retrograde Pathway in Motor Neurons, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 289, Pages: 16148-16163
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- Citations: 27
Palfi S, Gurruchaga JM, Ralph GS, et al., 2014, Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial, The Lancet, Vol: 383, Pages: 1138-1146, ISSN: 0140-6736
BackgroundParkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease.MethodsWe undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×10 7 transducing units [TU]); mid dose (4·0×10 7 TU); and high dose (1×10 8 TU). Inclusion criteria were age 48–65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinson's Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov, NCT00627588 and NCT01856439.Findings15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on–off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure we
Trabalza A, Eleftheriadou I, Sgourou A, et al., 2014, Enhanced Central Nervous System Transduction with Lentiviral Vectors Pseudotyped with RVG/HIV-1gp41 Chimeric Envelope Glycoproteins, JOURNAL OF VIROLOGY, Vol: 88, Pages: 2877-2890, ISSN: 0022-538X
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- Citations: 9
Lipinski DM, Barnard AR, Issa PC, et al., 2014, Vesicular Stomatitis Virus Glycoprotein- and Venezuelan Equine Encephalitis Virus-Derived Glycoprotein-Pseudotyped Lentivirus Vectors Differentially Transduce Corneal Endothelium, Trabecular Meshwork, and Human Photoreceptors, HUMAN GENE THERAPY, Vol: 25, Pages: 50-62, ISSN: 1043-0342
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- Citations: 20
Eleftheriadou I, Trabalza A, Ellison SMA, et al., 2013, Thy1.1, p75<SUP>NTR</SUP> or CAR receptor targeting by lentiviral vectors leads to retrograde transport and transduction of spinal motor neurons following peripheral delivery, Collaborative Congress of the European-Society-for-Gene-and-Cell-Therapy and the Spanish-Society-for-Gene-and-Cell-Therapy, Publisher: MARY ANN LIEBERT, INC, Pages: A37-A38, ISSN: 1043-0342
Ellison SM, Trabalza A, Tisato V, et al., 2013, Dose-dependent Neuroprotection of VEGF<sub>165</sub> in Huntington's Disease Striatum, MOLECULAR THERAPY, Vol: 21, Pages: 1862-1875, ISSN: 1525-0016
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- Citations: 17
Trabalza A, Georgiadis C, Eleftheriadou I, et al., 2013, Venezuelan equine encephalitis virus glycoprotein pseudotyping confers neurotropism to lentiviral vectors, GENE THERAPY, Vol: 20, Pages: 723-732, ISSN: 0969-7128
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- Citations: 11
Eleftheriadou I, Trabalza A, Ellison SM, et al., 2013, Gene Transfer to Motor Neurons with Novel Targeted Lentiviral Vectors, 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Publisher: NATURE PUBLISHING GROUP, Pages: S28-S28, ISSN: 1525-0016
Islam T, Hislop J, Carpentier D, et al., 2013, Rabies virus glycoprotein targets lentiviral vectors for retrograde vesicular transport in motor neurones, Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT), Publisher: MARY ANN LIEBERT INC, Pages: A23-A23, ISSN: 1043-0342
Ellison S, Trabalza A, Tisato V, et al., 2013, Dose dependent neuroprotection of VEGF<sub>165</sub> in Huntington's disease striatum, HUMAN GENE THERAPY, Vol: 24, Pages: A8-A8, ISSN: 1043-0342
Trabalza A, Sgourou A, Liao T-Y, et al., 2013, Enhanced CNS transduction with HIV-1 lentiviral vectors pseudotyped with chimeric envelope glycoproteins, Conference of the British-Society-for-Gene-and-Cell-Therapy (BSGCT), Publisher: MARY ANN LIEBERT INC, Pages: A28-A28, ISSN: 1043-0342
Kia A, Przystal JM, Nianiaris N, et al., 2012, Dual Systemic Tumor Targeting with Ligand-Directed Phage and <i>Grp78</i> Promoter Induces Tumor Regression, MOLECULAR CANCER THERAPEUTICS, Vol: 11, Pages: 2566-2577, ISSN: 1535-7163
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- Citations: 33
Eleftheriadou I, Trabalza A, Ellison SM, et al., 2012, Development of novel targeted lentiviral vectors for gene therapy of motor neuron diseases, Collaborative Congress of the European-Society-of-Gene-and-Cell-Therapy/French-Society-of-Cell-and-Gene-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: A123-A123, ISSN: 1043-0342
Islam TA, Hislop JN, Carpentier DCJ, et al., 2012, Trafficking characteristics of lentiviral vectors in motor neurons <i>in vitro</i>, Collaborative Congress of the European-Society-of-Gene-and-Cell-Therapy/French-Society-of-Cell-and-Gene-Therapy, Publisher: MARY ANN LIEBERT INC, Pages: A125-A125, ISSN: 1043-0342
Kia A, Przystal JM, Nianiaris N, et al., 2012, DUAL SYSTEMIC TUMOUR TARGETING WITH LIGAND-DIRECTED PHAGE AND <i>GRP78</i> PROMOTER INDUCES REGRESSION OF GLIOBLASTOMA, Conference of the British-Neuro-Oncology-Society (BNOS), Publisher: OXFORD UNIV PRESS INC, Pages: 5-5, ISSN: 1522-8517
Carpentier DCJ, Vevis K, Trabalza A, et al., 2012, Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a rabies/vesicular stomatitis virus chimeric envelope glycoprotein, GENE THERAPY, Vol: 19, Pages: 761-774, ISSN: 0969-7128
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- Citations: 30
Trabalza A, Georgiadis C, Ellison S, et al., 2011, Tropism of VEEV pseudotyped lentiviral vectors in the rodent brain, Publisher: MARY ANN LIEBERT INC, Pages: A109-A109, ISSN: 1043-0342
Carpentier DCJ, Vevis K, Trabalza A, et al., 2011, Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a Rabies/Vesicular Stomatitis Virus chimeric envelope glycoprotein, Publisher: MARY ANN LIEBERT INC, Pages: A19-A19, ISSN: 1043-0342
Jarraya B, Lepetit H, Ralph S, et al., 2010, Gene Therapy in Parkinson Disease: From Preclinical Studies in Primates to a Phase I Clinical Trial, HUMAN GENE THERAPY, Vol: 21, Pages: 764-765, ISSN: 1043-0342
Mitchell J, Paul P, Chen HJ, et al., 2010, Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase., PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCE (U S A), Vol: 107 (16), Pages: 7556-7561
We report a unique mutation in the D-amino acid oxidase gene (R199W DAO) associated with classical adult onset familial amyotrophic lateral sclerosis (FALS) in a three generational FALS kindred, after candidate gene screening in a 14.52 cM region on chromosome 12q22-23 linked to disease. Neuronal cell lines expressing R199W DAO showed decreased viability and increased ubiquitinated aggregates compared with cells expressing the wild-type protein. Similarly, lentiviral-mediated expression of R199W DAO in primary motor neuron cultures caused increased TUNEL labeling. This effect was also observed when motor neurons were cocultured on transduced astrocytes expressing R199W, indicating that the motor neuron cell death induced by this mutation is mediated by both cell autonomous and noncell autonomous processes. DAO controls the level of D-serine, which accumulates in the spinal cord in cases of sporadic ALS and in a mouse model of ALS, indicating that this abnormality may represent a fundamental component of ALS pathogenesis.
Jarraya B, Boulet S, Ralph GS, et al., 2009, Dopamine gene therapy for Parkinson’s disease in a nonhuman primate without associated dyskinesia, Science Translational Medicine, Vol: 1, Pages: 1-11, ISSN: 1946-6234
Jarraya B, Boulet S, Ralph GS, et al., 2009, Dopamine Gene Therapy for Parkinson's Disease in a Nonhuman Primate Without Associated Dyskinesia, SCIENCE TRANSLATIONAL MEDICINE, Vol: 1, ISSN: 1946-6234
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- Citations: 140
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