# Development and evaluation of cell therapy strategies for Alzheimer's disease.

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $445,680

## Abstract

Summary
Alzheimer’s disease (AD) is the major cause of dementia. Brain circuit dysfunctions underlie the memory
impairments of Alzheimer’s patients. Yet therapeutic approaches pursued in clinical trials failed to target
circuits directly. Currently there is no cure. Neuronal activity disruptions have been described as contributing
factors to the disease etiology and its progression. Anomalies in sleep-dependent brain rhythms, specifically
slow oscillations important for consolidation of memories during deep NREM sleep, have been reported in
Alzheimer’s patients. Converging evidence suggests that disruptions in slow oscillations are not simply
symptomatic of the disease but facilitate Alzheimer’s progression and might contribute to dementia. Therefore,
it is necessary to develop therapeutic strategies targeting restoration of circuit function, such as slow wave
activity, to restore cognitive impairments associated with sleep-dependent memory dysfunction.
Stem cell-based therapies hold promise for a number of neurological disorders including Alzheimer’s disease.
Since deficits in inhibitory tone underly slow oscillation disruptions, restoration of inhibitory tone through
transplantation of inhibitory interneuron progenitors might restore circuit function and slow Alzheimer’s
progression. Thus, isolation of MGE-derived interneuron progenitors and their transplantation into an animal
model of amyloidosis will be performed. We will systematically evaluate whether stem cell therapy restores
slow wave activity, slows neuropathophysiology and rescues sleep as well as memory impairments. We
propose to employ state-of-the-art methodology including widefield and multiphoton microscopy to monitor
circuit function as well as optogenetics to control neuronal activity with high temporal precision. Thus, as a
result of this work we will develop and evaluate the efficacy of stem cell therapy for the treatment of
Alzheimer’s disease in a mouse model of amyloidosis, thus opening the possibility of translating cell therapy as
a cure to slow AD progression in patients as part of a novel therapeutic approach.

## Key facts

- **NIH application ID:** 10524288
- **Project number:** 1R21AG075807-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Ksenia V. Kastanenka
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $445,680
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524288

## Citation

> US National Institutes of Health, RePORTER application 10524288, Development and evaluation of cell therapy strategies for Alzheimer's disease. (1R21AG075807-01A1). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10524288. Licensed CC0.

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