Safety and Efficacy of The Stem Cell Transplantation in Friedreich’s Ataxia: A Report of Three Cases

Riza Azeri; Duygu Koyuncu Irmak; Eda Sun; Erdal Karaöz

doi:10.15621/ijphy/2021/v8i1/903

Authors

Riza Azeri Istinye University, School of Medicine, Liv Hospital/Ulus, Department of Physical Therapy and Rehabilitation, Istanbul, Turkey.
Duygu Koyuncu Irmak Istinye University, School of Medicine, Department of Histology & Embryology, Istanbul, Turkey Topkapi Campus, Maltepe Mah., Teyyareci Sami Sk., No.3, Zeytinburnu, Istanbul, 34010, Turkey E-mail: Duygu.irmak@istinye.edu.tr
Eda Sun Istinye University, Stem Cell, and Tissue Engineering R&D Center, Istanbul, Turkey.
Erdal Karaöz Istinye University, School of Medicine, Department of Histology & Embryology, Istanbul, Turkey. Istinye University, Stem Cell, and Tissue Engineering R&D Center, Istanbul, Turkey. Istinye University, 3D Bioprinting Design & Prototyping R&D Center, Istanbul, Turkey. Liv Hospital/Ulus, Center for Stem Cell and Regenerative Therapies (LivMedCell), Istanbul, Turkey.

DOI:

https://doi.org/10.15621/ijphy/2021/v8i1/903

Keywords:

Friedreich’s ataxia, Hereditary Ataxia, Cellular Treatment, Regenerative Medicine, Stem Cell.

Abstract

Background: Friedreich’s ataxia is a progressive degenerative disorder caused by deficiency of the frataxin protein. Expanded GAA repeats in intron 1 of the FXN gene lead to its heterochromatinization and transcriptional silencing. Strategies being trialed to treat Friedreich’s ataxia include drugs that improve mitochondrial function and reduce oxidative injury. It has been shown that mesenchymal stem cell (MSC)-derived factors can restore cellular homeostasis and function to frataxin deficient cells.
Case Summary: Here, we report three FRDA cases treated with four consecutive allogeneic transplantations of umbilical cord-derived MSCs with 30 days interval, upon per patient regulatory approvals for advanced cellular therapy.
Outcome Measures: The cases were followed up after the treatment in means of the therapeutic effect of the cellular treatment by attenuating the neurological findings and gene expression parameters.
Conclusions: Closely followed promising safety and efficacy outcomes demonstrated that the MSC treatment for FRDA might positively affect the clinical results caused by the defect in this genetic-based disease.

References

Koeppen AH. Friedreich’s ataxia: Pathology, pathogenesis, and molecular genetics. J Neurol Sci. 2011;303(1-2):1-12.

Schulz JB, Boesch S, Bürk K, et al. Diagnosis and treatment of Friedreich ataxia: A European perspective. Nat Rev Neurol. 2009;5(4):222-234.

Koeppen AH. Neuropathology of the inherited ataxias. In: The Cerebellum and Its Disorders. ; 2010:387-406.

Bürk K, Schulz SR, Schulz JB. Monitoring progression in Friedreich ataxia (FRDA): The use of clinical scales. J Neurochem. 2013;126(SUPPL.1):118-124.

Hmadcha A, Martin-Montalvo A, Gauthier BR, Soria B, Capilla-Gonzalez V. Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy. Front Bioeng Biotechnol. 2020;8.

J. Braga Osorio Gomes Salgado A, L. Goncalves Reis R, Jorge Carvalho Sousa N, et al. Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine. Curr Stem Cell Res Ther. 2010;5(2):103-110.

Subramony SH, May W, Lynch D, et al. Measuring Friedreich ataxia: Interrater reliability of a neurologic rating scale. Neurology. 2005;64(7):1261-1262.

Dai A, Baspinar O, Yesilyurt A, et al. Efficacy of stem cell therapy in ambulatory and nonambulatory children with Duchenne muscular dystrophy – Phase I–II. Degener Neurol Neuromuscul Dis. 2018;8:63-77.

Tsai YA, Liu RS, Lirng JF, et al. treatment of spinocerebellar ataxia with mesenchymal stem cells: A phase I/IIa clinical study. Cell Transplant. 2017;26(3):503-512.

Oliveira Miranda C, Marcelo A, Silva TP, et al. Repeated Mesenchymal Stromal Cell Treatment Sustainably Alleviates Machado-Joseph Disease. Mol Ther. 2018;26(9):2131-2151.

Tajiri N, Staples M, Kaneko Y, Kim SU, Zesiewicz TA, Borlongan C V. Autologous stem cell transplant with gene therapy for Friedreich ataxia. Med Hypotheses. 2014;83(3):296-298.

Cook A, Giunti P. Friedreich’s ataxia: Clinical features, pathogenesis and management. Br Med Bull. 2017;124(1):19-30.

Hamidian Jahromi S, Estrada C, Li Y, Cheng E, Davies JE. Human Umbilical Cord Perivascular Cells and Human Bone Marrow Mesenchymal Stromal Cells Transplanted Intramuscularly Respond to a Distant Source of Inflammation. Stem Cells Dev Published online. 2018:scd.2017.0248.

Das AK, Abdullah BJJ Bin, Dhillon SS, Vijanari A, Anoop CH, Gupta PK. Intra-arterial allogeneic mesenchymal stem cells for critical limb ischemia are safe and efficacious: Report of a phase i study. World J Surg. 2013;37(4):915-922.

Pandolfo M. Frataxin deficiency and mitochondrial dysfunction. Mitochondrion 2002;2(1-2):87-93.

Aids to the Examination of the Peripheral Nervous System LONDON: HER MAJESTY’S STATIONERY OFFICE.; 1976.