# A small molecule p75NTR ligand to treat post-stroke mixed dementia

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2020 · $191,875

## Abstract

Mixed dementia is a complex form of dementia in which heterogeneous disease states co-­exist, the most 
common being pathologic characteristics of vascular dementia (VaD), such as chronic stroke infarcts, alongside 
pathologic characteristics of Alzheimer’s disease (AD). It is unknown precisely how many patients presently 
diagnosed with a particular type of dementia actually have mixed dementia, however post-­mortem analyses 
suggest that the condition may be present in nearly 50% of patients clinically diagnosed with AD. Yet despite the 
frequent co-­existence of VaD and AD, little is known about how these diseases influence each other, in part due 
to the lack of adequate animal models of mixed dementia, and there are no proven disease modifying therapies. 
 
To address this need, the goal of this proposal is to test if a first-­in-­class small molecule, orally bioavailable p75 
neurotrophin receptor (p75NTR) ligand, LM11A-­31, currently in Phase IIa clinical trials for the treatment of AD, 
also has efficacy in two different mouse models of post-­stroke mixed dementia. The first, is an innovative model 
of post-­stroke mixed dementia in which in the weeks following stroke, aged wildtype (wt) mice exhibit cholinergic 
neurodegeneration along with the appearance of neuritic plaques resembling those found in AD (Aim 1). The 
second, is a transgenic mouse model of mixed dementia in which aged AβPPL/S mice that have undergone a 
stroke develop more severe AD pathology than their age-­matched counterparts (Aim 2). In both of these models, 
mice also develop delayed cognitive impairments in the weeks after stroke. Positive results obtained here would 
be the first validation that p75NTR is an effective therapeutic target in two post-­stroke mixed dementia models, 
and could fast-­track LM11A-­31 into post-­stroke mixed dementia clinical testing.

## Key facts

- **NIH application ID:** 9895609
- **Project number:** 5R21AG062781-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Thuy-Vi Vu Nguyen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,875
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895609

## Citation

> US National Institutes of Health, RePORTER application 9895609, A small molecule p75NTR ligand to treat post-stroke mixed dementia (5R21AG062781-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895609. Licensed CC0.

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