RNA-targeted therapeutics in arterial hypertension

Area of Science:

• Cardiovascular Medicine
• Pharmacogenomics
• RNA Therapeutics

Background:

• Hypertension affects millions globally, with many patients unresponsive to current treatments due to resistance or poor adherence.
• Resistant hypertension and complex comorbidities necessitate innovative therapeutic strategies.
• RNA-targeted therapeutics offer a precision medicine approach for managing hypertension.

Purpose of the Study:

• To review the safety and efficacy of RNA-targeted nucleic acid therapeutics for hypertension.
• To explore novel treatments like zilebesiran and IONIS-AGT-LRX targeting angiotensinogen synthesis.
• To assess the potential of RNA-based drugs as long-acting alternatives to traditional antihypertensives.

Main Methods:

• Review of preclinical and clinical trials on RNA-targeted therapeutics for hypertension.
• Analysis of safety and efficacy data for small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs).
• Examination of mechanisms of action, including targeting hepatic synthesis of angiotensinogen.

Main Results:

• RNA-based drugs like zilebesiran and IONIS-AGT-LRX demonstrate potential in targeting AGT mRNA and reducing angiotensinogen levels.
• Subcutaneous RNA injections offer advantages such as target specificity and prolonged action.
• Current evidence is limited, with ongoing research in preclinical and clinical phases.

Conclusions:

• RNA-targeted therapeutics represent a promising avenue for hypertension management, particularly for patients with resistant disease or compliance issues.
• Further research is required to establish long-term cardiovascular outcomes, target organ protection, and mortality benefits.
• These therapies are not suitable for hypertensive emergencies and require more extensive clinical validation.