# Triagonist Peptide Therapeutics for Neuroprotection

> **NIH NIH R41** · VELUM, INC. · 2021 · $259,613

## Abstract

Project Summary
Morbidity associated with neuronal degeneration and dysfunction poses an increasing public
health burden. Among the wide range of etiologies that result in neuronal dysfunction, including
chronic conditions such as Alzheimer’s and Parkinson’s disease and vascular dementias, one
major cause that has been largely unnoticed but is increasingly recognized as a major concern is
traumatic brain injury (TBI). Even mild TBI (mTBI), which is highly prevalent and underestimated
in sport related injuries especially in American football and soccer and in the military, can have
persistent, and sometimes progressive, long-term debilitating effects. There is now evidence that
even a single traumatic brain injury, beyond causing reversible short-term defects, can precipitate
or accelerate age-related other neurodegenerative disease entities as noted above. The unmet
need is to develop a neuroprotective or disease-modifying therapy that can slow or halt disease
progression.
Recently, a synthetic monomeric peptide compound that acts as an agonist for three separate
receptors (“triagonist”), GLP-1R (glucagon-like peptide-1 receptor), GIPR (glucose-dependent
insulinotropic polypeptide receptor) and the glucagon receptor that control and direct glucose
metabolism, seems to have beneficial neurotrophic and neuroprotective effects useful for
conferring neuroprotection and mitigating the behavioral deficits in animal models of TBI and
Alzheimer’s disease.
We have invented chemical modifications at the N-terminal end of this triagonist peptide that
confer high chemical stability while conserving native potency and efficacy. Furtheremore, these
and other peptide modifications that rely on side chain attachments open the door for the design
of further improved peptide hormone analogs that are specifically designed to facilitate access to
the brain and protect neuronal cells. Such compounds will provide candidate therapeutics that
can move into the translational pipeline, to be pursued in subsequent phase II studies that will
initially focus on developing a treatment for mTBI.
We will synthesize a library of peptides and select for high potency target receptor activation and
maximized access to the brain. Moving further through the screening funnel, candidates will be
further prioritized based on their ability to rescue neuronal cells from oxidative stress and
glutamate excitotoxicity–induced cell death, and based on drug-induced attenuation of microglial
neuroinflammation. The deliverable in phase I will be the identification of a lead candidate and a
backup compound. These molecules will provide the basis for future phase II studies to further
determine PK/PD, and to explore therapeutic effectiveness in behavioral studies with mouse
models of mTBI as a prelude to preclinical (and clinical) studies.

## Key facts

- **NIH application ID:** 10326283
- **Project number:** 1R41GM142448-01A1
- **Recipient organization:** VELUM, INC.
- **Principal Investigator:** KRISHNA KUMAR
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $259,613
- **Award type:** 1
- **Project period:** 2021-09-25 → 2023-09-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326283

## Citation

> US National Institutes of Health, RePORTER application 10326283, Triagonist Peptide Therapeutics for Neuroprotection (1R41GM142448-01A1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10326283. Licensed CC0.

---

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