# Discovering targeted modulator of microglial activity as a candidate treatment for FTD and related dementias.

> **NIH NIH R43** · APERTURE THERAPEUTICS, INC. · 2024 · $459,525

## Abstract

PROJECT SUMMARY/ABSTRACT
 Frontotemporal dementia, often classified as Alzheimer’s disease related dementia, is a devastating disease
with a common onset between the ages of 40 to 65 that affects estimated >50,000 people just in the US. The
disease is a result of progressive degeneration of frontal and temporal lobes of the brain that can result in wide
variety of devastating symptoms including severe behavioral changes, speech and language problems, motor
disorders, and survival of 3-12 years, but no therapies slowing the progression of this age-related
neurodegenerative disease are available.
 We propose undertaking a project to rapidly discover a novel oligonucleotide therapeutic for direct modulation
of a genetically validated target involved in pathologic neuroinflammation. Microglia-driven neuroinflammation
has emerged as a critical pathologic mechanism in FTD and other age-related neurodegenerative diseases. We
found that our target expression level is significantly increased in FTD-ALS, which is the most severe version of
FTD. Consistently with published literature from other neurodegenerative diseases, we find that the lower
expression of the genetic target is correlated with longer patient survival, and its hypomorphic gene variant is
associated with late disease onset. This project leverages our high-throughput iPSC platform with diverse genetic
models of FTD to provide robust functional evidence for further development of the candidate drug.
 Successful completion of the proposed drug discovery project will deliver a candidate therapeutic for FTD
that will be ready for in vivo studies. The mission of our company is to efficiently deliver novel therapeutics to
patients with devastating age-related diseases using our lean company model and high-throughput, automated
drug discovery platform anchored in human genomic data paired with clinical measurements.

## Key facts

- **NIH application ID:** 10920288
- **Project number:** 1R43NS137874-01
- **Recipient organization:** APERTURE THERAPEUTICS, INC.
- **Principal Investigator:** Martin Jacko
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $459,525
- **Award type:** 1
- **Project period:** 2024-07-02 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920288

## Citation

> US National Institutes of Health, RePORTER application 10920288, Discovering targeted modulator of microglial activity as a candidate treatment for FTD and related dementias. (1R43NS137874-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10920288. Licensed CC0.

---

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