Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial

  title={Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial},
  author={Barry H. Greenberg and Javed Butler and G. Michael Felker and Piotr Ponikowski and Adriaan A. Voors and Akshay S. Desai and Denise D Barnard and Alain Bouchard and Brian E. Jaski and Alexander Richard Lyon and Janice M. Pogoda and Jeffrey J. Rudy and Krisztina Maria Zsebo},
  journal={The Lancet},

New insights into SERCA2a gene therapy in heart failure: pay attention to the negative effects of B-type natriuretic peptides

The current knowledge of SERCA2a gene therapy for heart failure is summarised, potential interaction between BNP levels and therapeutic effects ofSERCA 2a gene transfer is analysed and directions for future research to solve the identified problems are provided.

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

The results from the 5 patients at 3 years follow up 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.

Randomized Clinical Trials of Gene Transfer for Heart Failure with Reduced Ejection Fraction

The safety data from four randomized clinical trials of gene transfer in patients with symptomatic HFrEF suggest that this approach can be conducted with acceptable risk, despite invasive delivery techniques in a high-risk population.

Intracoronary Sarcoplasmic Reticulum Calcium-ATPase Gene Therapy in Advanced Heart Failure Patients with reduced Ejection Fraction: A Prospective Cohort Study

Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduces the number of recurrent and terminal events and improves the clinical course of advanced heart failure patients with reduced ejection fraction.

Cardiac Remodeling: The Course Towards Heart Failure-II. Diagnostic and Therapeutic Approaches

  • D. Cokkinos
  • Medicine, Biology
    Myocardial Preservation
  • 2019
With left ventricular assist device (LVAD) placement, improved results are reported with regard to both weaning from mechanical circulation support and overall survival and with respect to therapy, pharmaceutical treatment is still evolving.

Role of Targeted Therapy in Dilated Cardiomyopathy: The Challenging Road Toward a Personalized Approach

The recently proposed Morphology, Organ Involvement, Genetic, Etiology, Stage of disease nomenclature aims to better classify the multifactorial pathogenesis of DCM including upstream causes such as genetic variants and acquired diseases that interact and lead to overlapping disease-driving molecular mechanisms that finally impair myocardial function.

The function and significance of SERA2a in congestive heart failure: an analysis of gene therapy trials.

The function and significance of SERCA2a in CHF is illustrated, and possible causes of the controversial clinical trials results are analyzed, with the aim of stimulating future research on the relationship between SERca2a and CHF.

Gene Therapy in Cardiac Disease

The basic principles of gene transfer for cardiac disease are touched upon, including discussion of different vectors and delivery methods, and gene-based therapeutic interventions that have been tested clinically in patients are reviewed, primarily focusing on randomized, placebo-controlled clinical trials.



Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): A Phase 2 Trial of Intracoronary Gene Therapy of Sarcoplasmic Reticulum Ca2+-ATPase in Patients With Advanced Heart Failure

The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca2+-ATPase in advanced heart failure, supporting larger confirmatory trials.

Long-Term Effects of AAV1/SERCA2a Gene Transfer in Patients With Severe Heart Failure: Analysis of Recurrent Cardiovascular Events and Mortality

After a single intracoronary infusion of AAV1/SERCA2a in patients with advanced heart failure, positive signals of cardiovascular events persist for years, and no safety concerns were noted during the 3-year follow-up.

AAV-mediated gene therapy for heart failure: enhancing contractility and calcium handling

Results of recent clinical trials using recombinant adeno-associated virus (AAV) gene delivery offer the promise, for the first time, that heart failure can be reversed, and a “quiet revolution” may end up being one of the most significant and remarkable breakthroughs in modern medical practice.

Improvement in Survival and Cardiac Metabolism After Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase in a Rat Model of Heart Failure

It is shown that unlike inotropic agents that improve contractile function at the expense of increased mortality and worsening metabolism, gene transfer of SERCA2a improves survival and the energy potential in failing hearts.

Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals

Cardiac recirculation delivery of AAV2/1SERCA2a elicited a dose-dependent improvement in cardiac performance determined by left ventricular pressure analysis, and brain natriuretic peptide expression was reduced consistent with reversal of the HF molecular phenotype.

Concomitant intravenous nitroglycerin with intracoronary delivery of AAV1.SERCA2a enhances gene transfer in porcine hearts.

It is demonstrated that IV infusion of NTG significantly improves cardiac gene transfer efficiency in porcine hearts and resulted in increased viral transduction efficiency, both in terms of messenger RNA (mRNA) as well as protein levels in the whole left ventricle (LV) compared to control animals.

DNA Content in End-Stage Heart Failure.

  • BeltramiDi Loreto CFinatoYan
  • Medicine, Biology
    Advances in clinical pathology : the official journal of Adriatic Society of Pathology
  • 1997
Observations in this investigation are consistent with recent results documenting that in the presence of overload conditions the myocytes may retain their capacity to proliferate throughout life and this growth reserve mechanism may become operative in response to severe myocardial dysfuntion and overt failure.