# Understanding Frontotemporal Dementia Using Drosophila and iPSC Models

> **NIH NIH RF1** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $2,086,468

## Abstract

ABSTRACT
Dementia in aging populations poses a major global health challenge in years to come. In addition to Alzheimer’s
disease (AD), frontotemporal dementia (FTD) is another major form of presenile dementia caused by focal
degeneration of the prefrontal and/or temporal lobes. FTD patients show changes in personality, social
behaviors, or language production. Currently, effective treatments for FTD still remain elusive and the underlying
pathogenic mechanisms are poorly understood. The identification of many genes whose mutations are
associated with FTD offers an exciting entry point. Among them a GGGGCC (G4C2) repeat expansion in the first
intron of C9ORF72 is the most common cause of FTD. This mutation is also the most common genetic cause of
amyotrophic lateral sclerosis (ALS), further highlighting the importance of understanding neurotoxicity caused
by expanded G4C2 repeats and dipeptide repeat (DPR) proteins translated from both sense and antisense repeat
RNAs. In this proposal, we will take advantage of both classical genetics of fruitfly Drosophila and cutting-edge
techniques that are applicable to patient neurons differentiated from induced pluripotent stem cells (iPSCs) to
identify and characterize potent genetic modifiers of disease phenotypes relevant to C9ORF72-FTD/ALS. These
mechanistic studies will help understand molecular pathways involved in these disorders and may also reveal
potential effective drug targets for therapeutic interventions.

## Key facts

- **NIH application ID:** 10389678
- **Project number:** 2RF1NS101986-06
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Fen-Biao Gao
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,086,468
- **Award type:** 2
- **Project period:** 2017-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389678

## Citation

> US National Institutes of Health, RePORTER application 10389678, Understanding Frontotemporal Dementia Using Drosophila and iPSC Models (2RF1NS101986-06). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10389678. Licensed CC0.

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