# Targeting GPR146 for the Treatment of Homozygous Familial Hypercholesterolemia

> **NIH NIH R43** · VESICLE THERAPEUTICS INC. · 2022 · $298,036

## Abstract

Project Summary
Vesicle Therapeutics Inc aims to develop and commercialize a new therapy for homozygous
familial hypercholesterolemia (hoFH). A majority of hoFH is caused by mutations in both alleles
of the gene encoding the LDL receptor (LDLR). Since the efficacy of both statins and PCSK9
antibody therapies largely depends on functional LDL receptors, patients with hoFH show limited
responses to these existing therapies. Other than recently approved evinacumab, an antibody
therapy against Angiopoietin-like 3 (ANGPTL3), few options are available to treat this disease.
There is still an unmet medical need for developing new targeted therapies to lower both LDL-C
and lipids in hoFH. GRP146 has recently emerged as an exciting and potential new therapeutic
target for hoFH. Our goal is to leverage our proprietary delivery technology to develop a new
GPR146 therapy for hoFH. The overall objective of this Phase I SBIR project is to demonstrate
that silencing of GPR146 by proprietary gectosome delivery of LwaCas13a/GPR146 crRNA is
efficacious in lowering both LDL-C and lipids with acceptable safety profile in mice, enabling a
new therapy for hoFH.

## Key facts

- **NIH application ID:** 10482589
- **Project number:** 1R43HL164233-01
- **Recipient organization:** VESICLE THERAPEUTICS INC.
- **Principal Investigator:** Donna PEAK
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $298,036
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10482589

## Citation

> US National Institutes of Health, RePORTER application 10482589, Targeting GPR146 for the Treatment of Homozygous Familial Hypercholesterolemia (1R43HL164233-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10482589. Licensed CC0.

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