Understanding and Targeting Pulmonary Arteriovenous Malformations Using Repurposed Drugs
Abstract
Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by multiple arteriovenous malformations (AVMs) which are direct connections between arteries and veins, bypassing the capillary bed. Severe epistaxis (nosebleeds) is the most common symptom, yet visceral AVMs in the brain (1-10 percent), lung (15-45 percent), liver and gastrointestinal tract cause significant morbidity and mortality due to embolic stroke, cerebral abscess, migraines, hemorrhagic stroke, seizures and life-threatening bleeding complications. In order to reduce the morbidity and mortality associated with HHT, we need a better understanding of HHT development and novel treatment approaches. Our aims are: Aim 1: To understand the cellular and molecular mechanisms of PAVM development in mice and to identify the cell behaviors and populations that give rise to PAVMs. Aim 2: To identify and target pathological downstream signaling in endothelial cells derived from iPSCs (iPSC-ECs) from HHT patients with visceral AVMs. Aim 3: To target pathological downstream signaling with repurposed drugs to prevent and reverse PAVMs in the mouse model. The short-term impact will be a better understanding of how AVMs form in the lung and potentially in other organs. The long-term impact will be the identification of potential novel treatments for AVMs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1148040
Entities
People
- Astrid Gillich
- David Stevenson
- Edda Spiekerkoetter
- Ross Metzger
Organizations
- Stanford University