Hyunmin Cho PhD

PI / Investigator:  Hyunmin Cho, PhD - Stanford University, USA

Award Type: General Research Grant – fara funding made possible through the generosity of the Chant Family Bequest.

Grant Title: Diagnostic and Mechanistic Validation of a Metabolic Biomarker Panel to Guide Therapeutic Interventions in Friedreich’s Ataxia

Lay Summary:

This proposal seeks to explore the therapeutic potential of hematopoietic stem cell transplantation (HSCT) in a mouse model of FA and identify the mechanisms of metabolic correction by HSCT.

For many years HSCT has been used to treat severe neurodegenerative diseases in children. Recent studies in mice have shown that HSCT may also be beneficial for treating Friedreich's ataxia (FRDA), a condition that affects the nervous system, heart, and muscles. The idea is that stem cells can become cells that act like microglia or macrophages in the body, which can help correct metabolic issues in cells affected by the disease by transferring healthy mitochondria. However, this idea is still controversial and needs more testing in a better model of FRDA. 

Our goal is to test if HSCT can help treat FRDA using a better mouse model of the disease and to investigate the role of the chemotherapy used before the transplant. Our initial data suggests that FRDA mice require less chemotherapy before the transplant, that cells with low frataxin expression (a protein that is reduced in FRDA) have better mitochondrial transfer, and that low-dose chemotherapy before HSCT can improve symptoms in FRDA mice. We plan to test HSCT's potential effectiveness by looking at how it affects cells and molecules in the human FXN YAC transgenic mouse model with more than 800 GAA trinucleotide repeats.

We will also study how cells transfer mitochondria in vitro and in vivo and identify potential mechanisms using unbiased approaches like single cell-RNA sequencing and proteomics.

If successful, our study will provide more evidence to support using HSCT to treat FRDA and may offer new insights into how cells can correct metabolic issues by transferring mitochondria.