# Induced Pluripotent Stem Cells and Drosophila Models of C9ORF72-Related FTD/ALS

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $469,838

## Abstract

Dementia is one of the greatest global health challenges we face in the 21st century. Frontotemporal dementia
(FTD) is the second most common form of dementia among people under the age of 60 and its pathogenic
mechanisms are poorly understood. FTD and amyotrophic lateral sclerosis (ALS), a predominantly motor
neuron disease, share many clinical, pathological, and genetic features. The rapid identification of an array of
genes that cause FTD/ALS has opened exciting opportunities to dissect shared pathogenic molecular
pathways that may be effective targets for therapeutic intervention. In this appalication, we study the most
common genetic cause of FTD/ALS, a GGGGCC repeat expansion in the C9ORF72 gene. This genetic
mutation may cause disease through multiple mechanisms, including neurotoxicity induced by dipeptide (DPR)
proteins generated through repeat-associated non-AUG (RAN) translation. To study these diverse pathogenic
mechanisms, we take advantage of the power of Drosophila genetics including genetic suppressors and
enhancers of different FTD/ALS disease genes. Such studies often reveal totally unexpected molecular
pathways that shed light on pathogenic mechanisms and suggest novel therapeutic targets. In addition, cortical
neurons differentiated from patient-specific induced pluripotent stem cells (iPSCs) and human patient brain
tissues will be used as a complementary approach. This integrated approach—combining genetic, cellular,
molecular, electrophysiological, and bioinformatics analyses—will enable us to make significant contributions
to dementia research in the years to come.

## Key facts

- **NIH application ID:** 9888450
- **Project number:** 5R01NS101986-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Fen-Biao Gao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $469,838
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888450

## Citation

> US National Institutes of Health, RePORTER application 9888450, Induced Pluripotent Stem Cells and Drosophila Models of C9ORF72-Related FTD/ALS (5R01NS101986-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9888450. Licensed CC0.

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