Gene therapy to restore electrophysiological function in heart failure

Area of Science:

• Cardiovascular Medicine
• Molecular Cardiology
• Gene Therapy

Background:

• Heart failure (HF) presents a significant global health challenge, leading to high morbidity and mortality.
• Current HF treatments carry risks of pro-arrhythmic activity and sudden cardiac death.
• Novel, safe, and effective therapies for HF patients remain a critical unmet need.

Purpose of the Study:

• To review recent advancements in cardiac gene therapy for treating arrhythmias in heart failure (HF).
• To provide an overview of gene-based strategies for modulating cardiac function and restoring heart rhythm.

Main Methods:

• Review of emerging cardiac gene therapy approaches.
• Analysis of gene-based strategies targeting myocardial conduction, repolarization, calcium cycling, and adrenergic signaling.
• Examination of molecular underpinnings of arrhythmogenic disorders.

Main Results:

• Gene therapy allows selective targeting of specific cardiac cell populations.
• Therapeutic effects can be precisely limited to required regions.
• Gene-based approaches demonstrate success in correcting abnormal excitability in atria, ventricles, and the conduction system.

Conclusions:

• Cardiac gene therapy holds potential to revolutionize the treatment of lethal arrhythmias in HF patients.
• Advances in understanding molecular origins of arrhythmias facilitate targeted gene-based interventions.
• Successful translation to human application could significantly improve HF patient outcomes.