# Mitochondrial Transfer to Treat SBMA Motor Neurons

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $459,250

## Abstract

Project Summary
 Spinal bulbar muscular atrophy (SBMA) exhibits mitochondrial abnormalities. We and other
investigators have shown that mitochondrial dysfunction in SBMA involves both loss and gain of function from
the mutant androgen receptor (AR), acting as a critical driver to motor neuron (MN) degeneration. The
proposed project aims to implement mitochondrial transfer to treat SBMA MNs. Our specific aims for this
project will be as follows. In Specific Aim 1, we will develop an isogenic human neural stem cell (NSC) model,
consisting of isogenic control, disease, and AR knockout lines. We will isolate extracellular vesicles (EVs)
secreted from different isogenic NSC lines and specify biological characteristics of these vesicles for new
biomarker identification. In Specific Aim 2, we will culture disease MNs by supplementing mitochondrial EVs
derived from the isogenic control NSCs. We will examine the EV uptake potential of disease MNs, track the
intracellular fate of transferred mitochondria in recipient neurons, and evaluate whether EV-mediated
mitochondrial transfer will attenuate SBMA pathology. This project will establish the rationale and validate the
feasibility of mitochondrial transfer as a novel neuron-type-specific therapeutic intervention for SBMA and
other related neurodegenerative and neurologic disorders.

## Key facts

- **NIH application ID:** 10985401
- **Project number:** 1R21NS135044-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Xia Feng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $459,250
- **Award type:** 1
- **Project period:** 2024-07-05 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985401

## Citation

> US National Institutes of Health, RePORTER application 10985401, Mitochondrial Transfer to Treat SBMA Motor Neurons (1R21NS135044-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10985401. Licensed CC0.

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