# Understanding of a neurophenotype in hemophilia A

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $108,850

## Abstract

Bleeding resulting from factor VIII deficiency (hemophilia A) can occur in any tissue including the brain. Current
treatments, including factor VIII (FVIII) replacement and recent novel therapeutics, focus primarily on joint
health. In spite of advancements in treatment options, disabilities remain. People with hemophilia suffer from
increased rates of mental health disorders compared to age and sex matched controls (45% vs. 18.5%). While
significant progress has been made in prevention and treatment of hemophilia-related joint and muscle disease
with current standards of care, there is a paucity of research in hemophilia A to understand, treat, or prevent
brain disease. The long-term goal is to find diagnostic and treatment approaches that address the mechanism
and structure of neurologic disease in hemophilia A. The objective of this proposal is to examine the role of
FVIII deficiency on neurologic function and structure. The central hypothesis is that cerebral microbleeds and
neuroinflammation lead to changes in brain structure, causing behavioral changes in hemophilia A mice. The
rationale underlying this proposal is that completion will identify mechanisms causing poor neurologic
outcomes in hemophilia A. The central hypothesis will be tested by pursuing three specific aims: Aim 1)
Examine cerebral microbleeds and neuroanatomy phenotypes in hemophilia A mice. Aim 2) Investigate glial
activation and neuroinflammation in hemophilia A mice. Aim 3) Identify the role of FVIII replacement in
neuropsychiatric behavioral phenotypes in hemophilia A mice. We will pursue these aims using innovative
quantitative neuroimaging and gene transfer techniques to evaluate brain structure and function in hemophilia
animal model over time. The proposed research is significant because we will gain insights into the
neuroanatomic changes and neuroinflammatory pathways impacted in a model of FVIII deficiency. The
expected outcome of this work is that lack of FVIII will result in significant neurologic abnormalities. The results
will have an important positive impact because they will establish a better understanding of the developing
brain structure and function in FVIII deficiency, and long-term will improve cognitive, psychiatric, and quality of
life outcomes for people with hemophilia A.

## Key facts

- **NIH application ID:** 11047015
- **Project number:** 3R01HL146392-04S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Janice MarieRose Staber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $108,850
- **Award type:** 3
- **Project period:** 2020-05-07 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047015

## Citation

> US National Institutes of Health, RePORTER application 11047015, Understanding of a neurophenotype in hemophilia A (3R01HL146392-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11047015. Licensed CC0.

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