# Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders

> **NIH NIH R01** · MONTCLAIR STATE UNIVERSITY · 2022 · $731,471

## Abstract

Project Summary
 Age-related loss of memory remains a disease for which there are no effective treatments.
Data suggests that an enzyme found in a specific region of the brain associated with memory,
phosphodiesterase 11A (PDE11A), is increasingly expressed as humans age, and that levels of
key signaling molecules in the brain that are substrates for this enzyme decrease in tandem,
leading to the hypothesis that PDE11A is directly responsible for this effect. Our experiments with
mice lacking PDE11A revealed that these animals behave and reproduce normally and do not
suffer from the same age related loss of memory as their wild type littermates. This data
collectively leads to the hypothesis that PDE11A may be a valuable target for study as a means
to treat age-related loss of memory.
 There are no known potent and selective PDE11A inhibitors. A number of other PDE
enzymes are under investigation or have been studied for various psychiatric and
neurodegenerative diseases, indicating that this family can be targeted by small molecules. A
novel screening method using yeast that express human PDE11A identified a number of good
starting points. Some of these hits demonstrated excellent selectivity for PDE11A with the
potential to be optimized to provide the first potent, selective PDE11A inhibitors with a profile that
will allow us to investigate these compounds in mouse models of age-related behavior and
memory.

## Key facts

- **NIH application ID:** 10401488
- **Project number:** 5R01AG067836-03
- **Recipient organization:** MONTCLAIR STATE UNIVERSITY
- **Principal Investigator:** CHARLES S. HOFFMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $731,471
- **Award type:** 5
- **Project period:** 2020-09-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401488

## Citation

> US National Institutes of Health, RePORTER application 10401488, Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders (5R01AG067836-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401488. Licensed CC0.

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