# VIRAL DELIVERED CARDIAC REGENERATION

> **NIH NIH R43** · JAAN BIOTHERAPEUTICS, INC. · 2021 · $52,000

## Abstract

PROJECT SUMMARY
Ischemic heart disease (IHD) is the single largest cause of death in the industrialized world and contributor to
the development of Heart Failure (HF) in adults 1-2. IHD can be caused by a myocardial infarction (MI), which
limits coronary blood flow to the heart, causing ischemia and ultimately irreversible death of cardiomyocytes.
The size of a myocardial infarct correlates with the degree of deterioration of heart function 3, compromise of
contractile reserve, and over time the likelihood of mortality from HF 4. Prompt restoration of arterial perfusion
with thrombolytic and antiplatelet therapy during percutaneous coronary intervention has led to a decline in acute
mortality from MI. However, the prevalence of HF among survivors has augmented, because irreversible
cardiomyocyte death results in a residual inducible ischemia and permanent scarring. A major pathologic
problem is the failure of human adult cardiomyocytes to regenerate themselves endogenously following a MI.
This is compounded by a lack of adjunctive treatments, pharmacologic or cellular, that can be administered in
conjunction with reperfusion to stimulate regeneration of heart muscle and prevent the transition to HF. The
effective promotion of endogenous cardiomyocyte regeneration in the ischemic heart would potentially offer a
powerful new treatment for MI and its adverse pathophysiologic consequences. Inhibition of a specific
combination of four MicroRNAs (miRs); miR-99, miR-100, let-7a and let-7c, is a critical regulator of
cardiomyocyte dedifferentiation and proliferation in mammals 6. JBT has designed and tested an adeno
associated virus known as JBT-miR2, which allows for temporal, cardiac and non-integrative expression of
inhibitors to these four miRs. In preliminary studies in young mice with cardiac Ischemic Reperfusion (IR) injury
the efficacy and safety of a single dose of JBT-miR2 administered by intravenous injection at the time of
reperfusion was compared with Control virus. JBT-miR2 increased heart function and decreased cardiac
volumes at 2-weeks post IR with a corresponding ~47% reduction in scar tissue at 8-weeks post-IR compared
with control virus. To continue with Research and Development required for clinical trials it is necessary to
confirm the efficacy and safety in clinically translational larger aged animals. The Specific Aims of this Phase I
SBIR grant are to: 1: Conduct a dose range finding efficacy, safety and PK study of JBT-miR2 in middle aged
mini-pigs with IR injury, evaluating pleiotropic effects and mechanism of action. Significant, reproducible,
clinically relevant end-point changes in measures of cardiac dimension and function are expected in JBT-miR2
treated animals compared to Control virus. 2. Develop and validate PK and in vitro bioactivity assays. Assess
for immunogenicity, neutralizing antibodies, and viral particle titer levels to determine viral shedding in pigs. A
Target Product Profile will be drafted, with an underst...

## Key facts

- **NIH application ID:** 10377777
- **Project number:** 3R43HL154884-01S1
- **Recipient organization:** JAAN BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Bhawanjit K Brar
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $52,000
- **Award type:** 3
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377777

## Citation

> US National Institutes of Health, RePORTER application 10377777, VIRAL DELIVERED CARDIAC REGENERATION (3R43HL154884-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10377777. Licensed CC0.

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