# Calpastatin Peptide-based Calpain Inhibitor as a Traumatic Brain Injury Therapeutic

> **NIH NIH R43** · NEUROTHERANOSTICS, INC. · 2020 · $269,618

## Abstract

Abstract:
TBI is a leading cause of death and long-term disability worldwide. Although TBI is a significant
medical crisis, there are no FDA-approved pharmacological therapies that have been shown to
improve functional outcomes. The long-term goal of this project is to improve the immediate
and long-term outcomes of patients inflicted with severe TBI. Successful translation of the
therapy to the clinical care of patients with TBI would have an enormous direct impact on
function, wellness, and overall quality of life of victims of TBI, while shifting the current clinical
treatment paradigm to one that includes a restorative thrust. The product of this SBIR, B27-
HYD is an intravenous (IV) peptide drug, used in conjunction with the current standard of care,
administered to patients within hours of their suffering a severe TBI. The following two specific
aims will be pursued: 1) Determine the dose-response effects of intravenous B27-HYD on
a TBI biomarker panel, as well as the drug's effects on general health and physiological
measurements in sham and severe TBI rats. Milestone: A safe and effective IV dose of B27-
HYD that results in a minimum 40% reduction of 3 out of 5 pharmacodynamic TBI biomarkers
(calpain-mediated proteolytic breakdown products of αII-spectrin, GFAP, CRMPs, GAP-43, and
TDP-43). Effects of B27-HYD on arterial blood pressure, heart rate, body and head
temperature, and blood chemistry (blood gases, glucose) will be determined; and 2)
Demonstrate that a safe and effective dose of B27-HYD administered in the correct
timeframe protects brain cell and tissue, and improves recovery from cognitive and
emotional dysfunction after severe TBI. Milestone: A minimum 35% brain cell and tissue
protection, 35% reduction in the sensorimotor deficits (mNSS) and 40% overall improvement in
cognitive and emotional deficits (Morris water maze, Elevated Plus Maze, Forced Swimming
Test) will be criteria for success to move on to Phase II. As an outcome of the proposed SBIR
Phase I investigations, we expect that a safe and effective IV dose of B27-HYD, that
significantly reduces TBI biomarkers, will i) increase brain cell survival, ii) enhance brain repair
and regeneration, and iii) lead to marked improvement in cognitive and emotional functions.
After successful completion of our Phase I feasibility study, we plan to confirm the in vivo
efficacy of B27-HYD in a swine model of severe TBI. We have assembled a team of
neuroscientists, neurosurgeons, neuroprotective/neurorestorative drug development scientists
and regulatory experts with expertise and experience in TBI pathology, preclinical drug
development and regulatory experience to pursue the translational research outlined in this
proposal.

## Key facts

- **NIH application ID:** 10002114
- **Project number:** 5R43NS107043-02
- **Recipient organization:** NEUROTHERANOSTICS, INC.
- **Principal Investigator:** JOHN Y ANAGLI
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $269,618
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002114

## Citation

> US National Institutes of Health, RePORTER application 10002114, Calpastatin Peptide-based Calpain Inhibitor as a Traumatic Brain Injury Therapeutic (5R43NS107043-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10002114. Licensed CC0.

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