# Development of a small-molecule that enhances tripartite synapses for Alzheimers disease

> **NIH NIH U01** · OHIO STATE UNIVERSITY · 2020 · $1,552,548

## Abstract

Project Summary
The best correlate of memory deficits in Alzheimer’s disease (AD) patients is not Aβ plaque burden or
neurofibrillary tangles, but synapse loss, which is thought to occur early in the disease process before
the onset of clinical symptoms. We have developed a novel compound called M3 that can effectively
enhance structural and functional plasticity of synapses. This compound has been proved to provide
significant benefits in two mouse models of AD (APPSw/Ind mice and rTg4510 mice), including improved
cognitive functions, restored synaptic integrity, reduced neurodegeneration, reduced tau phosphorylation
and neurofibrillary tangles, and reduced amyloid plaques. M3 has excellent potency, solubility, stability,
specificity, and thus far no overt safety concerns. M3 meets all Late Stage Entry Criteria. In Year 1, we
will focus on IND-enabling studies and IND preparation and filing. Our milestones are (i) completion of
IND-enabling studies, (ii) production of a GMP batch for clinical studies, and (iii) active IND. In Year 2, we
will focus on a single ascending dose (SAD) study. Our milestones are (i) IRB approval, (ii) completion of
SAD study, and (iii) MTD and single dose PK established. In Year 3, we will focus on a multiple
ascending dose (MAD) study. Our milestones are (i) completion of MAD study and (ii) MTD and repeat
dose PK established.

## Key facts

- **NIH application ID:** 10045319
- **Project number:** 1U01AG068822-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** CHIEN-LIANG GLENN LIN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,552,548
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045319

## Citation

> US National Institutes of Health, RePORTER application 10045319, Development of a small-molecule that enhances tripartite synapses for Alzheimers disease (1U01AG068822-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10045319. Licensed CC0.

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