# Promoting adult hippocampal neurogenesis using antisense oligonucleotides as an Alzheimer's disease therapy

> **NIH NIH R43** · BOLDEN THERAPEUTICS, INC. · 2022 · $497,550

## Abstract

PROJECT SUMMARY
There is an enormous need for therapeutics to prevent and treat Alzheimer's disease (AD). Adult Hippocampal
Neurogenesis (AHN) is critical for normal learning and memory, but it declines in patients with AD. Work in
animal models has underscored the role of AHN in improving cognition in the face of AD pathology. Thus,
restoring AHN has emerged as an attractive target for an AD therapy. Augmenting AHN in the diseased brain
is widely considered a potential therapeutic modality for the treatment of AD as well as for other disease states
characterized by diminished neurogenesis e.g., frontotemporal dementia, treatment-resistant depression, post
traumatic stress disorder, and stroke. However, drug development efforts to date have lacked sufficient
specificity to selectively increase AHN without perturbing other stem cell regulatory mechanisms. In this Phase
I effort, Bolden Therapeutics will test exon-skipping antisense oligonucleotides (ASOs) against an undisclosed
target expressed in neural stem cells to increase AHN. These candidate exon-skipping ASOs successfully skip
the target region of interest in cultured cells and demonstrate favorable characteristics. We will use these
ASOs in wild-type and AD mouse models to evaluate their effect on AHN, disease pathology, and cognition.
Exon-skipping ASOs have emerged as effective and safe agents for regulating alternative splicing in the CNS.
Determining in vivo efficacy of our candidate compounds is a critical step towards developing a highly targeted,
safe and effective therapeutic for promoting AHN and improving cognition in AD. Following these studies, the
exon-skipping ASOs will be ready for IND-enabling experiments and rapid preclinical development as we work
towards developing a safe and effective therapy for AD and other disorders of impaired cognition via increasing
AHN.

## Key facts

- **NIH application ID:** 10484703
- **Project number:** 1R43AG078093-01
- **Recipient organization:** BOLDEN THERAPEUTICS, INC.
- **Principal Investigator:** Anne Valat
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $497,550
- **Award type:** 1
- **Project period:** 2022-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484703

## Citation

> US National Institutes of Health, RePORTER application 10484703, Promoting adult hippocampal neurogenesis using antisense oligonucleotides as an Alzheimer's disease therapy (1R43AG078093-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10484703. Licensed CC0.

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