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Updated: May 6, 2026
08:37
Purification of the Sarco-Endoplasmic Reticulum Ca2+-ATPase from Rabbit Muscle
Published on: March 21, 2025
894
Targeting sarcoplasmic reticulum calcium ATPase by gene therapy
Judith K Gwathmey1, Armen Yerevanian, Roger J Hajjar
1Cardiovascular Research Center, Icahn School of Medicine , New York, NY 10029.
Human Gene Therapy
|October 30, 2013
Summary
Gene therapy targeting SERCA2a shows promise for heart failure. Upregulating this calcium pump improved cardiac function and symptoms in a clinical trial, offering a new therapeutic avenue.
Area of Science:
- Cardiology
- Molecular Biology
- Gene Therapy
Background:
- Heart failure incidence is rising, necessitating novel therapeutic strategies beyond pharmacologic treatments.
- Abnormal calcium cycling, particularly reduced sarcoplasmic reticulum calcium ATPase (SERCA2a) activity, is a hallmark of failing human myocardium.
- SERCA2a plays a critical role in regulating myocardial contractility via calcium reuptake into the sarcoplasmic reticulum.
Purpose of the Study:
- To evaluate the safety and efficacy of gene therapy using SERCA2a as a target for heart failure treatment.
- To assess the impact of SERCA2a gene delivery on myocardial function and clinical outcomes in heart failure patients.
Main Methods:
- Utilized adeno-associated virus (AAV) vectors for gene delivery of SERCA2a.
- Conducted a Phase I clinical trial (CUPID) to assess Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease.
- Administered SERCA2a gene therapy via percutaneous delivery.
Main Results:
- Adeno-associated virus-mediated SERCA2a upregulation improved myocardial function in preclinical animal models.
- The CUPID study demonstrated persistent transgene expression of SERCA2a.
- Persistent SERCA2a expression was associated with significant improvements in biochemical markers and clinical symptoms of heart failure.
Conclusions:
- Gene therapy targeting SERCA2a represents a promising new approach for managing heart failure.
- SERCA2a gene delivery can lead to sustained functional and symptomatic benefits in patients with cardiac disease.
- Advancements in gene vector technology are paving the way for safer and more effective genetic therapies for cardiovascular conditions.
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