# Image-guided intra-arterial delivery of stem cells to repair brain damage after TBI

> **NIH VA I01** · BALTIMORE VA MEDICAL CENTER · 2024 · —

## Abstract

It is estimated that traumatic brain injury (TBI) accounts for over 2 million emergency department visits per
year, and nearly 300,000 require hospitalization and treatment (CDC data). Those who serve in the military are
at significant risk for TBI, with 414,000 cases reported among US service members between 2010-2019.
Consequences of TBI are often severe, including suffering for the victim, lost productivity, and burden on public
health systems, with the costs of hospitalization and rehabilitation growing, as well as current inadequate
treatments. Unfortunately, many patients develop lifelong neurological deficits. As the understanding of the
pathomechanism of TBI increases, attractive therapeutic targets are identified. Hence, there is hope of
developing new therapeutic strategies that could be implemented early to halt the ongoing cascade of damage
and at later stages, afford repair of brain damage.
 Pathomechanism of TBI is complex with multiple factors contributing to neurological deficits. TBI
triggers a strong and immediate inflammatory insult, with so-called “danger signals” or danger-associated
molecular patterns (DAMPs) being potent activators of local immune responses, mediating secondary brain
damage - especially adenosine triphosphate (ATP) and its receptor, P2X purinoceptor 7 (P2X7), whose
blocking has been studied with some success. However, following systemic administration, accumulation of
these macromolecules in the brain is hugely ineffective. Over the last two decades, our research has focused
on improving brain targeting with intra-arterial route being the most effective - as it facilitates minimally invasive
administration of high concentrations of drugs with immediate access within the entire lesion. Indeed, we
confirmed experimentally that even during acute stage after TBI intraarterial targeting of brain lesion is feasible.
This approach is ideal to address the needs of preventing TBI damages in the acute phase. As for the chronic
effects of TBI, recent studies focusing on war Veterans with TBI have revealed a preponderance of white
matter abnormalities.
 Our group has worked extensively with glial restricted progenitor (GRP) cells; and we demonstrated
quite spectacular therapeutic effects following transplantation in dysmyelinated mice. We have shown that
intra-arterially delivered GRPs can cross the blood-brain barrier; and thus, serve as a carrier for the local
production of neuroinflammation-blocking nanobodies in brain parenchyma. Here we propose the “block-and-
repair” therapy to address both the acute phase inflammation and the chronic phase white matter damage after
TBI. In this strategy, GRPs will be bioengineered with mRNA encoding a potent P2X7 nanobody to be
secreted in situ to block inflammation, and GRPs will mature to repair white matter injury after TBI. To improve
brain targeting for immediate effect, we will inject the cells using our established image-guided intra-arterial
technique. Our previous work ...

## Key facts

- **NIH application ID:** 10702032
- **Project number:** 1I01BX005768-01A2
- **Recipient organization:** BALTIMORE VA MEDICAL CENTER
- **Principal Investigator:** Piotr Walczak
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10702032

## Citation

> US National Institutes of Health, RePORTER application 10702032, Image-guided intra-arterial delivery of stem cells to repair brain damage after TBI (1I01BX005768-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10702032. Licensed CC0.

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