# Biomarkers of Cerebral Cavernous Angioma with Symptomatic Hemorrhage (CASH)

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $689,695

## Abstract

Biomarkers of Cerebral Cavernous Angioma with Symptomatic Hemorrhage (CASH)
PROJECT SUMMARY
Cerebral cavernous angioma (CA) is a capillary microangiopathy affecting more than a million Americans,
predisposing them to a premature risk of brain hemorrhage. Fewer than 200,000 cases who have suffered a
recent symptomatic hemorrhage (SH) are most likely to re-bleed again with serious clinical sequelae, and are
the primary focus of therapeutic development. Genetic mechanisms of CA have been extensively studied, and
consequent signaling aberrations in the neurovascular unit. These include proliferative dysangiogenesis, blood-
brain barrier hyperpermeability, inflammation and immune mediated processes, anticoagulant vascular domain,
and gut microbiome-driven mechanisms. Plasma levels of molecules reflecting these mechanisms and measures
of vascular permeability and hemorrhage leak on magnetic resonance imaging (MRI) have been correlated with
CA hemorrhage in pilot studies. It would be desirable to optimize these biomarkers to accurately diagnose CASH,
to prognosticate the risk of future SH, and to monitor cases after a bleed and in response to therapy. This would
influence clinical management, and select higher risk cases for clinical trials. Additional candidate biomarkers
are emerging from ongoing mechanistic and differential transcriptome studies, which would be expected to
further enhance the sensitivity and specificity of diagnosis and prediction of CASH. Weighed combinations of
levels of plasma proteins and characteristic micro-ribonucleic acids (miRNA) may further strengthen biomarker
associations. Plasma biomarkers may reflect (and potentially replace) more cumbersome and expensive imaging
biomarkers for monitoring CA hemorrhage. We here assemble leading clinical CA researchers and propose to
deploy advanced statistical and computational biology approaches (including supervised machine learning) for
the integration of novel candidate biomarkers, rejecting non-correlated candidates, and determining the best
clustering and weighing of combined biomarker contributions. In Specific Aim 1 we assess these biomarkers in
a large CA cohort from multiple sites, to discover the best plasma biomarkers and validate them in sex, age and
relevant clinical subgroups. In Specific Aim 2 we compare changes in MRI measures of vascular permeability
and hemorrhage with plasma biomarkers over time. In Specific Aim 3 we query the biomarkers in non-CA
subjects, to identify potential confounders in the clinical context. This project leverages the synergy of established
CA research consortia, and integrates analytic and computational biology expertise to develop blood tests for
better CASH diagnosis and prognosis. The project tests a novel integrational approach of biomarker
development in a mechanistically defined cerebrovascular disease with a relevant context of use. This approach
is applicable to other neurological diseases with similar pathobiologic features.

## Key facts

- **NIH application ID:** 10055845
- **Project number:** 1R01NS114552-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** ISSAM A AWAD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $689,695
- **Award type:** 1
- **Project period:** 2020-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055845

## Citation

> US National Institutes of Health, RePORTER application 10055845, Biomarkers of Cerebral Cavernous Angioma with Symptomatic Hemorrhage (CASH) (1R01NS114552-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10055845. Licensed CC0.

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