# A Novel Cyclic Peptide-Based Treatment for TBI

> **NIH NIH R01** · RHODE ISLAND HOSPITAL · 2020 · $516,120

## Abstract

PROJECT SUMMARY
Traumatic brain injury (TBI) is a devastating medical condition that affects more than 1.7 million civilians in the
US and represents an unmet clinical need. Effective therapies are urgently needed, as TBI is associated with
high rates of hospitalization, mortality, and disability. Previous clinical trials have failed to demonstrate
therapeutic efficacy in patients with TBI. Due to the complex nature of the pathophysiological events
accompanying TBI, an effective treatment necessitates the use of drugs with complementary therapeutic
effects directed against multiple pathological mechanisms.
We have developed a new cyclic peptide-based drug—CN2097—that possesses such properties. When
administered peripherally, CN2097 crosses the blood-brain barrier to selectively target PSD-95, an intracellular
scaffolding protein required for synapse strengthening (long term potentiation, LTP). CN2097 acts to potentiate
brain-derived neurotrophic factor (BDNF) signaling pathways required for neuroprotection and learning.
CN2097 produces a prolonged activation of the enzymes involved in memory processes to lower the threshold
for LTP, making this compound suited to treat the memory and executive functioning deficits in TBI patients. In
addition, CN2097 interferes with glutamate-mediated excitotoxic cell death and is the first in this class of
compounds to have anti-neuroinflammatory properties. This suggests that CN2097, by simultaneously redu-
cing excitotoxic damage and neuroinflammation, and facilitating synaptic plasticity, is a new multifunctional
drug with a significant therapeutic potential to curtail neuronal death and facilitate functional recovery after TBI.
There are three major goals of this project that focus on translational (preclinical), mechanistic, and neuro-
behavioral aspects of post-traumatic treatment with CN2097. In Aim 1, we will assess the efficacy of CN2097
in mitigating secondary injury and reducing the loss of neural tissue resulting from TBI. The experiments will
also be conducted to establish the potential therapeutic time-window for delayed treatment with CN2097, and
to quantitatively assess the ability of CN2097 to cross the BBB and determine its distribution in the injured
brain. In Aim 2, we will assess the efficacy and mechanism by which CN2097 attenuates synaptic and
neuronal loss in the hippocampus and restores synaptic plasticity after TBI. Lastly (Aim 3), we will assess the
efficacy of CN2097 in improving neurobehavioral outcome.
The multifunctionality of CN2097 together with our initial preclinical data obtained in a rodent model of TBI
strongly suggest that this new drug will be highly efficacious in targeting complex secondary injury processes
resulting from neurotrauma.

## Key facts

- **NIH application ID:** 9962508
- **Project number:** 5R01NS094440-05
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** ADAM CHODOBSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $516,120
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962508

## Citation

> US National Institutes of Health, RePORTER application 9962508, A Novel Cyclic Peptide-Based Treatment for TBI (5R01NS094440-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9962508. Licensed CC0.

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