Angiotensin receptor blocking antibody fragments as next-generation therapeutics for preeclampsia

NIH RePORTER · NIH · R21 · $211,875 · view on reporter.nih.gov ↗

Abstract

Hypertensive disorders of pregnancy such as preeclampsia are among the most important contributors to maternal and fetal morbidity and mortality. Despite the prevalence and impact of these disorders, few effective treatment options exist. The most widely used and effective antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), cannot be used to treat pregnant patients because they cross the placenta and cause developmental abnormalities in the fetus. We propose to develop antibody fragments that can bind to the angiotensin receptor and block its signaling. Since the placenta does not transport proteins (with the exception of IgG), antibody fragment ARBs may be able to treat maternal hypertension while avoiding fetal toxicity. In this project, we will create and optimize antibody fragment ARBs, and we will perform functional characterization to define their molecular pharmacology. This work will serve as a foundation for future efforts to investigate the therapeutic potential of this new ARB class.

Key facts

NIH application ID
9948339
Project number
1R21HD101596-01
Recipient
HARVARD MEDICAL SCHOOL
Principal Investigator
Andrew Kruse
Activity code
R21
Funding institute
NIH
Fiscal year
2020
Award amount
$211,875
Award type
1
Project period
2020-03-16 → 2022-02-28