Imperial College London

ProfessorEricAlton

Faculty of MedicineNational Heart & Lung Institute

Chair in Gene Therapy
 
 
 
//

Contact

 

+44 (0)20 7594 7929e.alton

 
 
//

Assistant

 

Miss Samia Soussi +44 (0)20 7594 7980

 
//

Location

 

Emmanuel Kaye BuildingRoyal Brompton Campus

//

Summary

 

Publications

Publication Type
Year
to

600 results found

Taylor-Cousar JL, Boyd AC, Alton EWFW, Polineni Det al., 2023, Genetic therapies in cystic fibrosis, CURRENT OPINION IN PULMONARY MEDICINE, Vol: 29, Pages: 615-620, ISSN: 1070-5287

Journal article

Edmondson C, Westrupp N, Short C, Seddon P, Olden C, Wallis C, Brodlie M, Baxter F, McCormick J, MacFarlane S, Brooker R, Connon M, Ghayyda S, Blaikie L, Thursfield R, Brown L, Price A, Fleischer E, Hughes D, Donnelly C, Rosenthal M, Wallenburg J, Brownlee K, Alton EWFW, Bush A, Davies JCet al., 2023, Unsupervised home spirometry is not equivalent to supervised clinic spirometry in children and young people with cystic fibrosis: results from the CLIMB-CF study, Pediatric Pulmonology, Vol: 58, Pages: 2871-2880, ISSN: 1099-0496

BACKGROUND: Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID-19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic-based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested. METHODS: Data from participants in the Clinical Monitoring and Biomarkers to stratify severity and predict outcomes in children with cystic fibrosisc (CLIMB-CF) Study aged ≥ 6 years who had paired (±1 day) clinic and home forced expiratory volume in 1 s (FEV1 ) readings were analyzed. Variability during clinical stability over 6-months was assessed. Four devices from Vitalograph were tested using 1 and 3 L calibration syringes. RESULTS: Sixty-seven participants (median [interquartile range] age 10.7 [7.6-13.9] years) provided home and clinic FEV1 data pairs. The mean (SD) FEV1 % bias was 6.5% [±8.2%]) with wide limits of agreement (-9.6% to +22.7%); 76.2% of participants recorded lower results at home. Coefficient of variation of home FEV1 % during stable periods was 9.9%. Data from the testing of the handheld device used in CLIMB-CF showed a potential underread. CONCLUSION: In children and adolescents, home spirometry using hand-held equipment cannot be used interchangeably with clinic spirometry. Home spirometry is moderately variable during clinical stability. New handheld devices underread, particularly at lower volumes of potential clinical significance for smaller patients; this suggests that supervision does not account fully for the discrepancy. Opportunities should be taken to obtain dual device measurements in clinic, so that trend data from home can be utilized more accurately.

Journal article

Miah KM, Chan M, Griesenbach U, Alton EWFW, Hyde SC, Gill DRet al., 2023, Novel Buffer Formulations for Improved Recombinant Lentiviral Vector Stability and <i>In Vivo</i> Delivery to the Murine Lungs, Publisher: CELL PRESS, Pages: 760-760, ISSN: 1525-0016

Conference paper

Davies J, Morales S, Alton E, Martin Iet al., 2023, Lytic bacteriophage is a promising adjunct to common antibiotics across cystic fibrosis clinical strains and culture models of Pseudomonas aeruginosa infection, Antibiotics, Vol: 12, Pages: 1-14, ISSN: 2079-6382

Bacteriophages (phages) are antimicrobials with resurgent interest that are being investigated for the treatment of antibiotic refractory infection, including for Pseudomonas aeruginosa (Pa) lung infection in cystic fibrosis (CF). In vitro work supports the use of this therapy in planktonic and biofilm culture models; however, consistent data are lacking for efficacy across different clinical Pa strains, culture models, and in combination with antibiotics in clinical use. We first examined the efficacy of a 4-phage cocktail as an adjunct to our CF centre’s first-line systemic combination antibiotic therapy (ceftazidime + tobramycin) for 16 different clinical Pa strains and then determined subinhibitory interactions for a subset of these strains with each antibiotic in planktonic and biofilm culture. When a 4-phage cocktail (4 × 108 PFU/mL) was added to a ceftazidime-tobramycin combination (ceftazidime 16 mg/mL + tobramycin 8 mg/mL), we observed a 1.7-fold and 1.3-fold reduction in biofilm biomass and cell viability, respectively. The four most antibiotic resistant strains in biofilm were very susceptible to phage treatment. When subinhibitory concentrations of antibiotics and phages were investigated, we observed additivity/synergy as well as antagonism/inhibition of effect that varied across the clinical strains and culture model. In general, more additivity was seen with the phage-ceftazidime combination than with phage-tobramycin, particularly in biofilm culture, where no instances of additivity were seen when phages were combined with tobramycin. The fact that different bacterial strains were susceptible to phage treatment when compared to standard antibiotics is promising and these results may be relevant to ongoing clinical trials exploring the use of phages, in particular in the selection of subjects for clinical trials.

Journal article

Juarez-Molina C, Meng C, Morgan C, Padley S, Gill D, Hyde S, Alton EWFW, Griesenbach Uet al., 2022, Non-viral Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A189-A189, ISSN: 1043-0342

Conference paper

Bell RV, Clarke NK, Alton EWFW, Griesenbach Uet al., 2022, Regulated expression of secreted transgenes by pulmonary transplanted macrophages in mice, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A55-A55, ISSN: 1043-0342

Conference paper

Sinadinos A, Bell R, Meng C, Gill DR, Hyde SC, Griesenbach U, Alton EWFWet al., 2022, A lentiviral vector intranasal dosing strategy to control local and systemic expression of intracellular and secreted transgenic proteins in vivo, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A195-A195, ISSN: 1043-0342

Conference paper

Richardson VR, Clarke NK, Griesenbach U, Alton EWFWet al., 2022, Optimising the genetic modification of macrophages using a lentiviral vector for application in cellular therapies, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A43-A43, ISSN: 1043-0342

Conference paper

Fiore MJ, Bell RV, Hickmott JW, Alton EWFW, Griesenbach Uet al., 2022, Significant transgene repression using the dCas9-KRAB-MeCP2 repressor system, 29th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy (ESCGT), Publisher: MARY ANN LIEBERT, INC, Pages: A151-A152, ISSN: 1043-0342

Conference paper

King JA, Cunanan A, Aziz S, Morant S, Murphy R, Coates N, Alton E, Guest C, Davies JCet al., 2022, PAWS FOR THOUGHT: SNIFFER DOGS FOR INFECTION SURVEILLANCE IN NON-SPUTUM PRODUCING PEOPLE WITH CF, Winter Meeting of the British-Thoracic-Society (BTS), Publisher: BMJ PUBLISHING GROUP, Pages: A21-A21, ISSN: 0040-6376

Conference paper

McLachlan G, Alton EWFW, Boyd AC, Clarke NKK, Davies JCC, Gill DRR, Griesenbach U, Hickmott JWW, Hyde S, Miah KMM, Molina CJet al., 2022, Progress in Respiratory Gene Therapy, HUMAN GENE THERAPY, Vol: 33, Pages: 893-912, ISSN: 1043-0342

Journal article

Alton E, Lund-Palau H, Juarez-Molina C, Meng C, Bhargava A, Pilou A, Aziz K, Clarke N, Atsumi N, Ashek A, Wilson M, Takata M, Padley S, Gill D, Hyde S, Morgan C, Griesenbach Uet al., 2022, Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression, Molecular Therapy - Methods and Clinical Development, Vol: 25, Pages: 382-391, ISSN: 2329-0501

We have developed a novel lentiviral vector, pseudotyped with the F and HN proteins from Sendai virus (rSIV.F/HN), which produces long-lasting, high efficiency transduction of the respiratory epithelium. Here, we addressed whether this platform technology can secrete sufficient levels of a therapeutic protein into the lung to ameliorate a fatal pulmonary disease, as an exemplar of its translational capability. Pulmonary Alveolar Proteinosis (PAP) results from alveolar GM-CSF insufficiency, resulting in abnormal surfactant homeostasis and consequent ventilatory problems. Lungs of GM-CSF knockout mice were transduced with a single dose of rSIV.F/HN expressing murine (m)GM-CSF (1e5-92e7 TU/mouse); mGM-CSF expression was dose-related and persisted for at least 11 months. PAP disease biomarkers were rapidly and persistently corrected, but we noted a narrow toxicity/efficacy window. rSIV.F/HN may be a useful platform technology to deliver therapeutic proteins for lung diseases requiring long-lasting and stable expression of secreted proteins.

Journal article

Bell R, Clarke NK, Isalan M, Alton EWFW, Griesenbach Uet al., 2022, Regulated Expression of LentiviralVectors Following Administration of anInducing Molecule, 2022 ASGCT Annual Meeting, Publisher: Cell Press, Pages: 419-419, ISSN: 1525-0016

Conference paper

Clarke NK, Sergijenko A, Pineault K, Sinadinos A, Meng C, Griesenbach U, Alton EWFWet al., 2022, Ex Vivo Transduced Macrophages Engraft in the Lung Following Transplantation and Produce Therapeutic Levels of Secreted Proteins, American Society of Cell and Gene Therapy, Publisher: CELL PRESS, Pages: 405-405, ISSN: 1525-0016

Conference paper

Hickmott JW, Prasertsuk P, Bell RV, Chan M, Griesenbach U, Alton EWFWet al., 2022, Heterologous Signal Peptides Enhance Protein Secretion for Respiratory Gene Therapy, Publisher: CELL PRESS, Pages: 417-418, ISSN: 1525-0016

Conference paper

Sergijenko A, Pineault KM, Moiseenko A, Gill DR, Hyde SC, Kreuz S, Alton EWFW, Griesenbach Uet al., 2022, Development of Molecular Assays to Determine Lentiviral Vector-Mediated Transduction Efficiency in Airway Epithelial Cells, Publisher: CELL PRESS, Pages: 419-419, ISSN: 1525-0016

Conference paper

Bell RV, Clarke NK, Isalan M, Alton EWFW, Griesenbach Uet al., 2022, Regulated Expression of Lentiviral Vectors Following Administration of an Inducing Molecule, Publisher: CELL PRESS, Pages: 419-419, ISSN: 1525-0016

Conference paper

Balachandar S, Graves TJ, Shimonty A, Kerr K, Kilner J, Xiao S, Slade R, Sroya M, Alikian M, Curetean E, Thomas E, McConnell VPM, McKee S, Boardman-Pretty F, Devereau A, Fowler TA, Caulfield MJ, Alton EW, Ferguson T, Redhead J, McKnight AJ, Thomas GA, Aldred MA, Shovlin CLet al., 2022, Identification and validation of a novel pathogenic variant in GDF2 (BMP9) responsible for hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations, American Journal of Medical Genetics Part A, Vol: 188, Pages: 959-964, ISSN: 0148-7299

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular dysplasia, characterized by arteriovenous malformations (AVMs), mucocutaneous telangiectasia and nosebleeds. HHT is caused by a heterozygous null allele in ACVRL1, ENG, or SMAD4, which encode proteins mediating bone morphogenetic protein (BMP) signaling. Several missense and stop-gain variants identified in GDF2 (encoding BMP9) have been reported to cause a vascular anomaly syndrome similar to HHT, however none of these patients met diagnostic criteria for HHT. HHT families from UK NHS Genomic Medicine Centres were recruited to the Genomics England 100,000 Genomes Project. Whole genome sequencing and tiering protocols identified a novel, heterozygous GDF2 sequence variant in all three affected members of one HHT family who had previously screened negative for ACVRL1, ENG, and SMAD4. All three had nosebleeds and typical HHT telangiectasia, and the proband also had severe pulmonary AVMs from childhood. In vitro studies showed the mutant construct expressed the proprotein but lacked active mature BMP9 dimer, suggesting the mutation disrupts correct cleavage of the protein. Plasma BMP9 levels in the patients were significantly lower than controls. In conclusion, we propose that this heterozygous GDF2 variant is a rare cause of HHT associated with pulmonary AVMs.

Journal article

Edmondson C, Westrupp N, Seddon P, Olden C, Wallis C, Dawson C, Brodlie M, Baxter F, McCormick J, MacFarlane S, Rice D, Macleod A, Brooker R, Connon M, Ghayyda S, Blaikie L, Thursfield R, Brown L, Price A, Fleischer E, Itterman J, Hughes D, Barrett P, Surette M, Donnelly C, Mateos-Corral D, Padley G, Wallenburg J, Brownlee K, Alton EWFW, Bush A, Davies JCet al., 2022, The feasibility of home monitoring of young people with cystic fibrosis: results from CLIMB-CF, Journal of Cystic Fibrosis, Vol: 21, Pages: 70-77, ISSN: 1569-1993

BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.

Journal article

Bell RV, Isalan M, Alton EWFW, Griesenbach Uet al., 2021, Regulation of lentivirusā€mediated expression in a human airway model, ESGCT Collaborative Virtual Congress, Publisher: Mary Ann Liebert, ISSN: 1043-0342

Conference paper

Bell R, Faulkner N, Griesenbach U, Alton EWFWet al., 2021, Intravenous administration of F/HN pseudotyped lentiviral vector, ESGCT Collaborative Virtual Congress, Publisher: Mary Ann Liebert, ISSN: 1043-0342

Conference paper

Clarke N, Sinadinos A, Meng C, Alton E, Griesenbach Uet al., 2021, Ex vivo transduced macrophages produce therapeutic levels of secreted protein when transplanted to the lung, ESGCT Collaborative Virtual Congress, Publisher: Mary Ann Liebert, ISSN: 1043-0342

Conference paper

Hickmott JW, Prasertsuk P, Bell RV, Chan M, Griesenbach U, Alton EWFWet al., 2021, Modifying signal peptides for respiratory gene therapy with secreted proteins, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A39-A40, ISSN: 1043-0342

Conference paper

Bell RV, Isalan M, Alton EWFW, Griesenbach Uet al., 2021, Regulation of lentivirus-mediated expression in a human airway model, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A40-A40, ISSN: 1043-0342

Conference paper

Bell RV, Faulkner N, Griesenbach U, Alton EWFWet al., 2021, Intravenous administration of F/HN pseudotyped lentiviral vector, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A131-A131, ISSN: 1043-0342

Conference paper

Clarke NK, Sinadinos A, Meng C, Alton EWFW, Griesenbach Uet al., 2021, Ex vivo transduced macrophages produce therapeutic levels of secreted protein when transplanted to the lung, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A10-A10, ISSN: 1043-0342

Conference paper

Faulkner N, Alton EW, Griesenbach U, Kassiotis Get al., 2021, Reducing anti-vector humoral immunity through modulation of surface glycoprotein density, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A108-A109, ISSN: 1043-0342

Conference paper

Juarez-Molina CI, Lund-Palau H, Meng C, Gill D, Hyde S, Alton E, Griesenbach Uet al., 2021, Lentiviral vector/GM-CSF Gene Therapy for Autoimmune Pulmonary Alveolar Proteinosis, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A38-A38, ISSN: 1043-0342

Conference paper

Moiseenko A, Pineault K, Sergijenko A, Alton EWFW, Boyd AC, Davies JC, Gill DR, Griesenbach U, Hyde SC, McLachlan G, Hobbie S, Schuler M, Maier U, Thomas MU, Mennerich D, Kreuz Set al., 2021, Functional characterisation of an engineered next generation lentivirus vector for the treatment of cystic fibrosis, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A39-A39, ISSN: 1043-0342

Conference paper

Hickmott JW, Sinadinos AJ, Sergijenko A, Saleh AD, Nafchi NAM, Gamlen T, Gill DR, Hyde SC, Alton EWFW, Griesenbach Uet al., 2021, Single cell tools for measuring mRNA and protein expression for gene therapy, European Society of Gene and Cell Therapy Collaborative Virtual Congress (ESGCT), Publisher: MARY ANN LIEBERT, INC, Pages: A39-A39, ISSN: 1043-0342

Conference paper

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00155603&limit=30&person=true