Gene Therapy for Heart Failure

Heart failure is a chronic and progressive condition that affects millions of people worldwide. It occurs when the heart muscle is unable to pump enough blood to meet the body’s needs for oxygen and nutrients. Common causes of heart failure include coronary artery disease, hypertension, diabetes, cardiomyopathy, valvular heart disease, and arrhythmias. Symptoms of heart failure vary depending on its severity and type, but may include shortness of breath, fatigue, edema, chest pain, palpitations, and reduced exercise tolerance. Treatments for heart failure aim to improve symptoms, quality of life, and patient survival. These treatments include medications, devices, surgery, and lifestyle modifications. However, these therapies have limitations and drawbacks, including side effects, complications, high costs, and low patient compliance. Therefore, there is a pressing need for alternative or complementary approaches that can address the underlying causes and mechanisms of heart failure. Gene therapy offers a promising avenue in this regard. It can target specific genes or pathways involved in the pathogenesis or progression of heart failure. Additionally, gene therapy can enhance the heart’s endogenous repair and regeneration mechanisms. By doing so, gene therapy has the potential to restore the heart’s normal function and structure or prevent further deterioration. Moreover, it can reduce the adverse effects and complications associated with other therapies by minimizing the need for drugs or devices.

Fig.1 Vectors Used for Gene Therapy of Cardiac Disease (Greenberg B, 2017)

Features of Gene Therapy for Heart Failure

Gene therapy for heart failure boasts several features and benefits that position it as a promising option in the field. This innovative approach allows for the precise targeting of specific genes or pathways involved in the onset and progression of heart failure. For instance, gene therapy can be employed to modulate genes responsible for regulating cardiac contractility, hypertrophy, apoptosis, angiogenesis, fibrosis, inflammation, or metabolism. Furthermore, it can enhance the heart's inherent repair and regeneration mechanisms. By stimulating the growth or differentiation of cardiac stem cells, cardiomyocytes, or endothelial cells, gene therapy holds the potential to restore or prevent further deterioration of heart function and structure. What's more, this therapy can significantly reduce the necessity for, or complications associated with, other treatments by optimizing drug dosage or the implantation of medical devices. Gene therapy offers the distinct advantage of providing long-term or even permanent benefits. This is achieved through the integration or maintenance of stable expression of therapeutic genes. For instance, gene therapy can utilize integrating or non-integrating vectors to insert and maintain therapeutic genes within host cells. Additionally, inducible or regulated promoters can be employed to precisely control gene expression in response to specific conditions. Furthermore, tissue-specific or cell-specific promoters are used to ensure gene expression occurs exclusively in the target cells or tissues.

Research or Clinical Progress

Numerous studies and clinical trials have been conducted, and more are underway, to evaluate the feasibility and efficacy of gene therapy for heart failure. In Table 1, we provide a concise overview of some of the most relevant and recent studies and trials, focusing on their key findings and outcomes.

Table 1. The Most Relevant and Recent Studies or Trials on Gene Therapy for Heart Failure

Gene therapy for heart failure is still a developing field with many challenges and opportunities. More research is needed to identify the optimal target genes, vectors, delivery methods, and dosages for different types of heart failure. Moreover, more rigorous and large-scale clinical trials are required to establish the long-term safety and efficacy of gene therapy for heart failure. Gene therapy holds great potential to provide novel and effective treatments for patients with heart failure who have limited options with conventional therapies.

References

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