# The Use of Deferiprone to Improve Subarachnoid Hemorrhage Cognitive Outcome: U-DISCO

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $574,389

## Abstract

Project Summary:
Aneurysmal subarachnoid hemorrhage (aSAH) has a high mortality rate (~60%), with a large proportion of the
survivors becoming functionally dependent. aSAH survivors have long term cognitive deficits and memory
impairment in their productive years with major responsibilities with respect to work and family.
In a 30-year nationwide population-based cohort study using data from Danish medical databases, the authors
computed the absolute risks and hazard ratios (HR) of dementia up to 30 years after stroke. Compared with
the general population, the HR (95% confidence interval) for dementia among ischemic stroke survivors was
1.72 (1.66–1.77), 2.70 (2.53–2.89) after intracerebral hemorrhage, and 2.74 (2.45–3.06) after aSAH.
Why is that?? In aSAH subjects, accumulation of hemoglobulin (Hb) and non-heme iron (Fe) which are the
natural byproduct lysis of red blood cells leads to significant neuronal cells death. Several preclinical studies in
animals showed that both products lead to neuronal death and atrophy of any brain structures exposed to it
and specifically the hippocampus and amygdala. These data were replicated in human, where authors found,
the level of ferritin (Ft) in CSF, a reporter of the amount of Fe in brain, was found to strongly correlate with
progression to Alzheimer's disease (AD).
What is the mechanistic pathway of this process?? Our group showed that Hb is toxic to neuronal cells in
vitro and adding deferiprone (De) attenuated and reversed this effect significantly. We then confirmed these
results in a mouse model of intraventricular hemorrhage. Additionally, in a proof-of-concept study we showed
that De significantly decreased Ft in CSF (p<0.0001) suggesting a potential therapeutic effect. Furthermore,
others also showed in preclinical studies using different animal models, Fe chelating agents decrease Fe
content both in the subarachnoid space and intraventricular improving the functional and cognitive outcome in
these animals. Therefore, we propose this grant to test the hypothesis that deferiprone, a lipid soluble Fe
chelating agent and therefore diffuse easily across the blood-brain barrier, will significantly decrease Ft (a
reporter of total non-heme Fe content in CSF) in subjects with aSAH and hence improve cognitive function.
To test this hypothesis, we propose a phase 1/2a single-center randomized double-blinded placebo vs. De trial
that recruits and enrolls 66 subjects with aSAH who require placement of EVD as a standard of care. Subjects
will be randomized equally into 2 groups: A) placebo & B) 15 mg/kg bid for 21 days. Ft will be collected daily
from CSF. We will also test the cognitive changes using the Montreal Cognitive Assessment test along with a
battery of well-standardized and widely used cognitive tests that measure various aspects of cognitive and
behavioral functioning. We will also assess the volume of hippocampus and amygdala in this cohort and
compare them to a matched, historic control cohort...

## Key facts

- **NIH application ID:** 10637023
- **Project number:** 7R01AG068848-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** David M Hasan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $574,389
- **Award type:** 7
- **Project period:** 2022-06-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10637023

## Citation

> US National Institutes of Health, RePORTER application 10637023, The Use of Deferiprone to Improve Subarachnoid Hemorrhage Cognitive Outcome: U-DISCO (7R01AG068848-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10637023. Licensed CC0.

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