Imperial College London
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MrNicholasJohnson

Faculty of Medicine, School of Public Health

Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 1751nicholas.johnson

 
 
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Location

 

Stadium HouseWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lyon:2020:10.1038/s41434-020-0171-7,
author = {Lyon, A and Babalis, D and Morley-Smith, AC and Hedger, M and Suarez, Barrientos A and Foldes, G and Couch, LS and Chowdhury, RA and Tzortzis, KN and Peters, NS and Rog-Zielinska, EA and Yang, YH and Welch, S and Bowles, CT and Rahman, Haley S and Bell, AR and Rice, A and Sasikaran, T and Johnson, NA and Falaschetti, E and Parameshwar, J and Lewis, C and Tsui, S and Simon, A and Pepper, J and Rudy, JJ and Zsebo, KM and MacLeod, KT and Terracciano, CM and Hajjar, RJ and Banner, N and Harding, SE},
doi = {10.1038/s41434-020-0171-7},
journal = {Gene Therapy},
pages = {579--590},
title = {Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL},
url = {http://dx.doi.org/10.1038/s41434-020-0171-7},
volume = {27},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. Enrolled subjects were randomised to receive a single intracoronary infusion of 1x1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort, which may help guide future trial design.
AU  - Lyon,A
AU  - Babalis,D
AU  - Morley-Smith,AC
AU  - Hedger,M
AU  - Suarez,Barrientos A
AU  - Foldes,G
AU  - Couch,LS
AU  - Chowdhury,RA
AU  - Tzortzis,KN
AU  - Peters,NS
AU  - Rog-Zielinska,EA
AU  - Yang,YH
AU  - Welch,S
AU  - Bowles,CT
AU  - Rahman,Haley S
AU  - Bell,AR
AU  - Rice,A
AU  - Sasikaran,T
AU  - Johnson,NA
AU  - Falaschetti,E
AU  - Parameshwar,J
AU  - Lewis,C
AU  - Tsui,S
AU  - Simon,A
AU  - Pepper,J
AU  - Rudy,JJ
AU  - Zsebo,KM
AU  - MacLeod,KT
AU  - Terracciano,CM
AU  - Hajjar,RJ
AU  - Banner,N
AU  - Harding,SE
DO  - 10.1038/s41434-020-0171-7
EP  - 590
PY  - 2020///
SN  - 0969-7128
SP  - 579
TI  - Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device – the SERCA-LVAD TRIAL
T2  - Gene Therapy
UR  - http://dx.doi.org/10.1038/s41434-020-0171-7
UR  - https://www.nature.com/articles/s41434-020-0171-7
UR  - http://hdl.handle.net/10044/1/78835
VL  - 27
ER  -
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