# Cerebral hemorrhage risk in Hereditary Hemorrhagic Telangiectasia

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $330,014

## Abstract

Abstract
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by
arteriovenous malformations (AVMs) in the brain, lung and liver, causing life-threatening hemorrhage, stroke,
and heart failure. Intracranial hemorrhage (ICH) from brain AVMs (BAVMs) is the most feared complication and
remains a therapeutic and prevention challenge. Available treatment modalities for BAVMs are invasive and
their associated morbidity must be weighed against ICH risk. Though the mean rate of ICH from BAVMs in
HHT is relatively low, the distribution is wide, with a large range of risk. As such, clinical decisions for individual
patients require weighing the morbidity of treatment against the risk of poor outcomes, including ICH and
neurologic disability from BAVMs. Our first overarching goal is thus to identify BAVM patients at high risk of
poor outcomes to help guide clinical decision-making in individuals. We also propose to extend our
measurement of AVM bleeding risk in HHT to include the much more common bleeding phenotype in HHT,
chronic nasal bleeding, as we hypothesize that there are shared predictors of bleeding across affected organs
in HHT. Specifically, we will define the severe nasal bleeding phenotype (patient reported outcome, PRO) and
measure biomarkers, genetic modifiers and clinical predictors of bleeding severity. Several molecular pathways
have been linked to HHT and there has been a recent explosion of potential pharmacologic therapies for HHT
and AVMs, including anti-angiogenic, anti-inflammatory, immune modulating agents, and others. As the safety
and benefits of these therapies are assessed through trials for chronic bleeding in HHT, trials for BAVM
treatment in HHT become more plausible. We plan to establish clinical trial readiness for HHT and BAVM,
through development of bleeding severity measures and comprehensive brain outcomes measures.
We propose to leverage our established recruitment network, our large HHT cohort (N=2400, including 600
with BAVM, by end of Cycle 3), and progress made in the first two cycles characterizing genetic and clinical
predictors, to accomplish the following specific aims: (Aim 1) to identify predictors of brain outcomes in HHT
patients; (Aim 2) to define a severe bleeding phenotype in HHT for clinical trial readiness; and (Aim 3) to
identify genetic predictors and circulating biomarkers of severe bleeding and brain outcomes in HHT. Project 3
participants will be recruited through 16 HHT Treatment Centers and through the Patient Advocacy Group
(HHT Foundation International, CureHHT). The HHT investigator group will continue to work closely with the
HHTFI, as well as with the DMCC, leveraging the established DMCC web-based portal, data collection and
management protocols in place. The combined output of all three Aims will help guide clinical decision making
for BAVM patients and will poise the HHT scientific community to undertake clinical trials of newly available
pharmaco-t...

## Key facts

- **NIH application ID:** 10673823
- **Project number:** 5U54NS065705-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Marie E Faughnan
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $330,014
- **Award type:** 5
- **Project period:** 2009-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10673823

## Citation

> US National Institutes of Health, RePORTER application 10673823, Cerebral hemorrhage risk in Hereditary Hemorrhagic Telangiectasia (5U54NS065705-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10673823. Licensed CC0.

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