title: Autologous stem cell transplant with gene therapy for Friedreich ataxia.
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.
authors: 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.
authors: Naoki
authors: N
authors: Tajiri
authors: 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.
authors: Meaghan
authors: M
authors: Staples
authors: 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.
authors: Yuji
authors: Y
authors: Kaneko
authors: Department of Neurology, University of British Columbia, Vancouver, Canada.
authors: Seung U
authors: SU
authors: Kim
authors: 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.
authors: Theresa A
authors: TA
authors: Zesiewicz
authors: 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.
authors: Cesar V
authors: CV
authors: Borlongan
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D005621:Friedreich Ataxia / Q000503:physiopathology* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation; D033862:Iron-Binding Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology; D009474:Neurons / Q000378:metabolism; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D019680:Trinucleotide Repeat Expansion; D000096923:Frataxin
chemical_list: D033862:Iron-Binding Proteins; D000096923:Frataxin