The renin-angiotensin system (RAS) is a well-known hormone system that regulates blood pressure and fluid balance. Traditionally, it’s been understood that this system begins with the conversion of a liver-derived protein, angiotensinogen (AGT), by the enzyme renin, eventually producing angiotensin II (Ang II), a powerful compound that narrows blood vessels and raises blood pressure. However, new research has revealed alternate pathways for generating Ang II that don’t rely on renin. One of the most significant discoveries is a molecule called angiotensin-(1-12), or Ang-(1-12), which acts as a direct precursor to Ang II in both blood and tissues, especially the heart.

Researchers have developed a novel monoclonal antibody that specifically targets Ang-(1-12), blocking its ability to produce Ang II. This strategy offers a more targeted way to reduce Ang II levels, potentially avoiding drawbacks of current therapies. Early experiments in both normal and genetically modified hypertensive rats have shown that neutralizing Ang-(1-12) can reduce blood vessel constriction and may offer a promising new direction for managing high blood pressure.

Technology Overview

Current Challenges

Current blood pressure treatments target well-known steps in the RAS pathway, such as ACE inhibitors and Ang II blockers. While effective, these drugs often come with side effects, low patient adherence, and limited success in fully controlling hypertension. New therapies are being explored, including gene-silencing techniques that reduce AGT levels in the liver. However, these approaches might disrupt other important functions of AGT that are still being uncovered.

Our Innovation

Researchers have developed a first-in-class monoclonal antibody that selectively targets angiotensin-(1-12) [Ang-(1-12)], a non-canonical precursor of angiotensin II (Ang II), to disrupt a key pathway in blood pressure regulation. Unlike traditional antihypertensive drugs that focus on inhibiting ACE or blocking Ang II receptors, this antibody neutralizes Ang-(1-12) directly, interrupting the formation of Ang II at an earlier stage. This approach offers a novel therapeutic mechanism that may overcome limitations of current RAS-targeted treatments, including incomplete efficacy, poor adherence, and unwanted side effects. Preclinical studies in both normal and hypertensive rat models show that this antibody effectively reduces vascular contraction, suggesting potential utility in treating resistant or poorly controlled hypertension. 

Benefits of this Technology

  • Targets Ang-(1-12), bypassing reliance on renin and traditional RAS enzymes.
  • May offer better blood pressure control in patients unresponsive to current treatments.
  • Offers a more specific point of intervention, potentially minimizing off-target effects associated with ACE or renin inhibition.
  • Could be combined with existing antihypertensives for additive or synergistic effects.
  • Intervenes earlier in the Ang II production cascade, possibly preventing downstream damage to heart and kidneys

Stage of Development

The invention is currently in the preclinical proof-of-concept stage. Data from in vivo studies in Sprague Dawley rats and transgenic hypertensive rats expressing the human AGT gene demonstrate effective neutralization of Ang-(1-12) and reduced vascular contraction in ex vivo carotid artery ring models.