# Pharmacokinetic Assessment of Peptide-Based Therapy HV-3 for the Treatment of Huntington's Disease

> **NIH NIH R43** · JANUSQ, LLC · 2021 · $240,938

## Abstract

PROJECT SUMMARY/ABSTRACT
JanusQ, LLC is a startup biotech company, spun out of Case Western Reserve University, and developing
a peptide-based therapy for the treatment of mitochondrial dysfunction in Huntington’s Disease (HD). This
neurological disorder affects roughly 30,000 diagnosed patients in the US, and an additional 150,000 are at risk.
Currently, no proven, effective treatments for HD exists, and patients are relegated to therapies that alleviate
involuntary muscle movement and behavioral changes. Therapies that address the causative agent, the mutant
huntingtin protein (mtHtt), have not yet seen success in the clinic, and the mechanism by which mtHtt leads to
the disease state is poorly understood. Mutant huntingtin associates with mitochondria, triggering dysfunction
that leads to neurotoxicity. In multiple HD models valosin-containing protein (VCP) is recruited to mitochondria
where VCP associates with mtHtt and leads to excessive mitophagy and neuronal death. A newly designed
peptide, HV-3, disrupts VCP:mtHtt interactions, resulting in reduced aberrant mitophagy and improved neuronal
survival. When administered to HD animal models, HV-3 reduces behavioral and neuropathological phenotypes
and improves survival. However, very little is known about the pharmacokinetics (PK) of HV-3, making it difficult
to know whether or not this peptide is a suitable clinical candidate for the treatment of HD. The purpose of this
SBIR grant is to ascertain the PK characteristics of HV-3, making it possible determine whether it will be
necessary in future work to optimize the peptide to improve its PK characteristics. The project has two aims: (1)
To develop bioanalytical techniques for lead peptide HV-3. Various methods for efficiently extracting HV-3
from plasma and brain tissue in high yield (>80%) will be investigated. A method for the quantitation of HV-3
from various biological extracts will be developed and validated using tandem liquid chromatography mass
spectroscopy. An acceptable method will need to quantitate HV-3 reliably at sub-micromolar concentrations. (2)
To use the newly developed bioanalytical techniques to study the PK of HV-3 in vivo and ascertain its
readiness as a candidate for HD therapy. Plasma and brain tissue concentrations of HV-3 will be determined
at various time points after administration—via both intraperitoneal (IP) and subcutaneous (SQ) routes—at three
separate doses. These results will directly address our central hypothesis: does HV-3 have the PK characteristics
necessary for advancement to the clinic, or do specific properties require modification of the peptide? The
proposed work is the next logical step toward the long-term goal of developing a peptide therapy to improve
quality of life and survival of HD patients. The proposed work is commercially viable because current direct costs
of HD patients in the US is about $1B/year. A treatment for HD that improves the survival and wellbeing of
patients would reduce rel...

## Key facts

- **NIH application ID:** 10078211
- **Project number:** 1R43NS119006-01
- **Recipient organization:** JANUSQ, LLC
- **Principal Investigator:** Andrew Loring Schilb
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $240,938
- **Award type:** 1
- **Project period:** 2020-12-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10078211

## Citation

> US National Institutes of Health, RePORTER application 10078211, Pharmacokinetic Assessment of Peptide-Based Therapy HV-3 for the Treatment of Huntington's Disease (1R43NS119006-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10078211. Licensed CC0.

---

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