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.

Gene Therapy
A R LyonS E Harding

Abstract

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. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 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 at 3 years follow up, which confirmed that viral DNA was delivered to the faili...Continue Reading

References

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Citations

Jan 6, 2021·Pflügers Archiv : European journal of physiology·Satadru K LahiriXander H T Wehrens
Jan 9, 2021·The FEBS Journal·Kirstie A De Jong, Viacheslav O Nikolaev
Dec 31, 2020·Genes·Svenja Dannewitz ProssedaEdda Spiekerkoetter
Mar 7, 2021·International Journal of Molecular Sciences·Jing LiTingTing Hong
Apr 27, 2021·Frontiers in Physiology·Satvik MareeduGopal J Babu
May 26, 2021·Journal of Internal Medicine·H KorpelaS Ylä-Herttuala
May 23, 2021·Acta Physiologica·Almudena Val-BlascoMaria Fernández-Velasco

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Methods Mentioned

BETA
biopsy
PCR
electron
electron tomography
transfection

Clinical Trials Mentioned

NCT00534703

Software Mentioned

InForm Integrated Trial Management
CUPID2
CUPID
InForm Trial Management system

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