# Identifying the genetic basis of variably protease-sensitive prionopathy

> **NIH NIH R03** · BROAD INSTITUTE, INC. · 2022 · $66,800

## Abstract

PROJECT SUMMARY
First characterized one decade ago, VPSPr is a rare neurodegenerative disease that presents clinically as
Lewy body dementia or frontotemporal lobar degeneration but has been neuropathologically linked to deposits
of infectious but protease-sensitive prion protein (PrP) aggregates. VPSPr cases lack mutations in the prion
protein gene (PRNP) but 42% of cases have a positive family history, consistent with a genetic disease of
moderate penetrance. We will apply whole exome sequencing and deep targeted sequencing to query the
genetic basis of VPSPr. Identification of a genetic cause of VPSPr will aid in the differential diagnosis of prion
disease and Alzheimer’s-related dementias, validate new genomic technologies for understanding
neurodegeneration, and identify new cellular pathways that lead to neurodegenerative disease.

## Key facts

- **NIH application ID:** 10448659
- **Project number:** 1R03NS123786-01A1
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Eric Vallabh Minikel
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $66,800
- **Award type:** 1
- **Project period:** 2022-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448659

## Citation

> US National Institutes of Health, RePORTER application 10448659, Identifying the genetic basis of variably protease-sensitive prionopathy (1R03NS123786-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10448659. Licensed CC0.

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