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Med Hypotheses. 2014 Sep;83(3):296-8. doi: 10.1016/j.mehy.2014.05.022. Epub 2014 Jun 9.

Autologous stem cell transplant with gene therapy for Friedreich ataxia.

Author information

1
Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
2
Department of Neurology, University of British Columbia, Vancouver, Canada.
3
University of South Florida Ataxia Research Center, Department of Neurology, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
4
Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Electronic address: cborlong@health.usf.edu.

Abstract

We advance the overarching hypothesis that stem cell therapy is a potent treatment for Friedreich's ataxia (FRDA). Here, we discuss the feasibility of autologous transplantation in FRDA, highlighting the need for the successful isolation of the FRDA patient's bone marrow-derived mesenchymal stem cells, followed by characterization that these cells maintain the GAA repeat expansion and the reduced FXN mRNA expression, both hallmark features of FRDA. Next, we discuss the need for assessment of the proliferative capability and pluripotency of FRDA patient's bone marrow-derived mesenchymal stem cells. In particular, we view the need for characterizing the in vitro differentiation of bone marrow-derived mesenchymal stem cells into the two cell types primarily affected in FRDA, peripheral neurons and cardiomyocytes. Finally, we discuss the need to test the application of bone marrow-derived mesenchymal stem cells as potent autologous donor cells for FRDA. The demonstration of the functional correction of the mutated gene in these cells will be a critical endpoint of determining the potential of stem cell therapy in FRDA. We envision a gene-based cell transplant strategy as a likely therapeutic approach for FRDA, involving stable insertion of functional human bacterial artificial chromosomes or BACs containing the intact FXN gene into stem cells, thereafter leading to the expression of frataxin protein in differentiated neurons/cardiomyocytes.

PMID:
24962209
PMCID:
PMC4145018
DOI:
10.1016/j.mehy.2014.05.022
[Indexed for MEDLINE]
Free PMC Article
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