# Novel EPO peptide therapy for chronic rmTBI dependent neurodegeneration and neuroinflammation

> **NIH VA I01** · VA NEW JERSEY HEALTH CARE SYSTEM · 2022 · —

## Abstract

This project examines a treatment for chronic repeated mild traumatic brain injury (rmTBI). rmTBI is a
chronic neurodegenerative disease afflicting individuals who have received multiple concussive head injuries
such as soldiers and contact sport players. There is no known cure for this disease that is often marked by
progressive neurological deterioration. rmTBI can lead to memory loss, mood problems, suicidality, and
dementia. The disease is associated with chronic neuroinflammation, axonal injury and brain atrophy.
 There is extensive evidence that long-term inflammation worsens neurodegenerative disease. Our
laboratory has developed JM4, a novel immune/inflammatory regulatory agent. JM4 is a short peptide derived
from the cytokine erythropoietin. Whole molecule erythropoietin has well established neuroprotective and
immune/inflammatory modulating effects, however, its use in clinical settings is limited since it can lead to
dangerous polycythemic levels of red blood cells. JM4 crosses the blood-brain barrier and retains
erythropoietin's beneficial effects without the side effect of hematopoiesis. Preliminary studies showed that it
was highly effective in reducing the immune/inflammatory responses in models of experimental autoimmune
encephalomyelitis and that even a brief course of JM4 induced long term improvement. It also decreased
neuropathology and clinical deficit in acute traumatic brain injury. Furthermore, in a mouse model of
frontotemporal dementia, it reduced clinical signs, microglial and astrocytic activation and tauopathy. JM4 has
completed preclinical development and was recently approved by the FDA as an Investigational New Drug
(IND) for the treatment of acute multiple sclerosis flare-ups. This current study examines the hypothesis that
JM4 will have beneficial effects in slowing or reversing deficits in chronic rmTBI by profoundly reducing the
inflammatory response. Our preliminary data showed that JM4 can reduce chronic rmTBI even when
administered a year after the initial injuries.
 We will use a validated repeat weight drop mouse model of chronic rmTBI to evaluate the therapeutic
potential of JM4 in the following experiments:
SA1. We found that a JM4 dose of 10ug/day was effective therapy in animal models of tauopathy, MS, and
 acute TBI; however, the optimal dose of JM4 in chronic rmTBI may not be the same. Accordingly, we will
 establish a long duration JM4 dose response curve initiated at 12 months after injury. Animals will be
 tested for behavioral deficit at 1, 6, 12, and 18 months after impact and sacrificed at 18 months.
SA2. We will examine whether short-term pulse JM4 therapy may also be effective in chronic rmTBI. The
 experimental design will be identical to SA1, but JM4 therapy will be restricted to 30 days.
SA3. We believe that synaptic dysfunction is a major contributor to chronic cognitive deficit in TBI patients.
 To correlate cognitive performance with electrophysiological measures within subjects, synapt...

## Key facts

- **NIH application ID:** 10375442
- **Project number:** 5I01RX003347-02
- **Recipient organization:** VA NEW JERSEY HEALTH CARE SYSTEM
- **Principal Investigator:** Yun-Beom Choi
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375442

## Citation

> US National Institutes of Health, RePORTER application 10375442, Novel EPO peptide therapy for chronic rmTBI dependent neurodegeneration and neuroinflammation (5I01RX003347-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10375442. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*