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Efficacy and safety of primary and repeated therapy courses of Parkinson’s disease with autologous mesenchymal stromal cells in the long-term period

https://doi.org/10.29235/1814-6023-2024-21-1-68-78

Abstract

Parkinson’s disease (PD) is a chronic progressive disease. Currently, PD treatment is symptomatic. One of the promising directions changing the PD therapy course is the use of autologous multipotent mesenchymal stromal cells (MMSCs). Despite the encouraging results in various preclinical and clinical trials and proven safety, the cell therapy questions remain open, such as the choice of an optimal route of administration, dose, and frequency of treatment courses.

In the present study, the dynamics of PD motor and non-motor symptoms was assessed after the first and second cell therapy courses using MMSC injections via systemic and tandem methods during a long-term period. A positive therapy effect on the dynamics of motor and non-motor symptoms in patients with PD was revealed for an average of 6 months after one MMSC treatment course. The repeated MMSC treatment course has similar efficacy and safety to the first course and can be used to slow down the PD progression for a longer period.

About the Authors

V. A. Chуzhуk
Institute of Advanced Training and Retraining of Healthcare Personnel of Educational Institution “Belarusian State Medical University”
Belarus

Veranika A. Chуzhуk – Assistant

3/3, P. Browka Str., 220013, Minsk



М. М. Sialitski
Institute of Advanced Training and Retraining of Healthcare Personnel of Educational Institution “Belarusian State Medical University”
Belarus

Mikhail M. Sialitski – Ph. D. (Med.), Associate Professor

3/3, P. Browka Str., 220013, Minsk



V. V. Ponomarev
Institute of Advanced Training and Retraining of Healthcare Personnel of Educational Institution “Belarusian State Medical University”
Belarus

Vladimir V. Ponomarev – D. Sc. (Med.), Professor, Head of the Department.

3/3, P. Browka Str., 220013, Minsk



References

1. Schrag A., Jahanshahi M., Quinn N. How does Parkinson’s disease affect quality of life? A comparison with quality of life in the general population. Movement Disorders, 2000, vol. 15, pp. 1112–1118. https://doi.org/10.1002/1531-8257(200011)15:63.0.co;2-a

2. Zhang W., Wang T., Pei Zh., D. Miller S., Wu X., Block M. [et al.]. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB Journal, 2005, vol. 19, no. 6, pp. 533–542. https://doi.org/10.1096/fj.04-2751com

3. Levin O. S., Fedorova N. V. Parkinson’s disease. 5th ed. Moscow, MEDpress-inform Publ., 2012. 352 p. (in Russian).

4. Chaudhuri K. R., Healy D. G., Schapira A. H. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurology, 2006, vol. 5, no. 3, pp. 235–245. https://doi.org/10.1016/S1474-4422(06)70373-8

5. Herz D. M., Haagensen B. N., Christensen M. S., Madsen K. H., Rowe J. B., Løkkegaard A., Siebner H. R. The acute brain response to levodopa heralds dyskinesias in Parkinson disease. Annals of Neurology, 2014, vol. 75, no. 6, pp. 829–836. https://doi.org/10.1002/ana.24138

6. Salama M., Sobh M., Emam M., Abdalla A., Sabry D., El-Gamal M. [et al.]. Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson’s disease. Experimental and Therapeutic Medicine, 2017, vol. 13, no. 3, pp. 976‒982. https://doi.org/10.3892/etm.2017.4073

7. Chen D., Fu W., Zhuang W., Lv C., Li F., Wang X. J. Therapeutic effects of intranigral transplantation of mesenchymal stem cells in rat models of Parkinson’s disease. Journal of Neuroscience Research, 2017, vol. 95, no. 3, pp. 907‒917. https://doi.org/10.1002/jnr.23879

8. Chyzhyk V., Boika A., Ponomarev V. Assessment of non-motor symptoms of Parkinson’s disease in the long-term follow-up after the cell therapy. Available at: https://www.mdsabstracts.org/abstract/assessment-of-non-motor-symptomsof-parkinsons-disease-in-the-long-term-follow-up-after-the-cell-therapy (accessed 06.07.2023).

9. Glass J. D., Hertzberg V. S., Boulis N. M., Riley J., Federici T., Polak M. [et al.]. Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials. Neurology, 2016, vol. 87, no. 4, pp. 392–400. https://doi.org/10.1212/WNL.0000000000002889

10. Petrou P., Gothelf Y., Argov Z., Gotkine M., Levy Y. S., Kassis I. [et al.]. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurology, 2016, vol. 73, no. 3, pp. 337–344. https://doi.org/10.1001/jamaneurol.2015.4321

11. Berry J. D., Cudkowicz M. E., Windebank A. J., Staff N. P., Owegi M., Nicholson K. [et al.]. NurOwn, phase 2, randomized, clinical trial in patients with ALS. Neurology, 2019, vol. 93, no. 24, pp. e2294–e2305. https://doi.org/10.1212/WNL.0000000000008620

12. Petrou P., Kassis I., Ginzberg A., Halimi M., Yaghmour N., Abramsky O., Karussis D. Long-term clinical and immunological effects of repeated mesenchymal stem cell injections in patients with progressive forms of multiple sclerosis. Frontiers of Neurology, 2021, vol. 12, art. 639315. https://doi.org/10.3389/fneur.2021.639315

13. Vaquero J., Zurita M., Rico M. A., Aguayo C., Bonilla C., Marin E. [et al.]. Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline. Cytotherapy, 2018, vol. 20, no. 6, pp. 806–819. https://doi.org/10.1016/j.jcyt.2018.03.032

14. Hughes A. J., Daniel S. E., Kilford L., Lees A. J. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry, 1992, vol. 55, no. 3, pp. 181‒184. https://doi.org/10.1136/jnnp.55.3.181

15. Hoehn M. M. Parkinsonism: onset, progression, and mortality. Neurology, 1967, vol. 17, no. 5, pp. 427–442. https://doi.org/10.1212/wnl.17.5.427

16. Thuy C. Vu, Nutt J. G., Holford N. H. G. Progression of motor and nonmotor features of Parkinson’s disease and their response to treatment. British Journal of Clinical Pharmacology, 2012, vol. 74, no. 2, pp. 267–283. https://doi.org/10.1111/j.1365-2125.2012.04192.x

17. Liang X., Ding Y., Zhang Y., Tse H. F., Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives. Cell Transplantation, 2014, vol. 23, no. 9, pp. 1045–1059. https://doi.org/10.3727/096368913X667709

18. Fan X.-L., Zeng Q.-X., Li X., Li C.-L., Xu Z.-B., Deng X.-Q., Shi J., Chen D., Zheng S. G., Fu Q.-L. Induced pluripotent stem cell-derived mesenchymal stem cells activate quiescent T cells and elevate regulatory T cell response via NF-κB in allergic rhinitis patients. Stem Cell Research & Therapy, 2018, vol. 9, no. 1, art. 170. https://doi.org/10.1186/s13287-018-0896-z

19. Green D. R., Reed J. C. Mitochondria and apoptosis. Science, 1998, vol. 281, no. 5381, pp. 1309–1312. https://doi.org/10.1126/science.281.5381.1309

20. Whone A. L., Kemp K., Sun M., Wilkins A., Scolding N. J. Human bone marrow mesenchymal stem cells protect catecholaminergic and serotonergic neuronal perikarya and transporter function from oxidative stress by the secretion of glial-derived neurotrophic factor. Brain Research, 2012, vol. 1431, pp. 86–96. https://doi.org/10.1016/j.brainres.2011.10.038

21. Ohkouchi S., Block G. J., Katsha A. M., Kanehira M., Ebina M., Kikuchi T., Saijo Y., Nukiwa T., Prockop D. J. Mesenchymal stromal cells protect cancer cells from ROS-induced apoptosis and enhance the Warburg effect by secreting STC. Molecular Therapy, 2012, vol. 20, no. 2, pp. 417–423. https://doi.org/10.1038/mt.2011.259

22. Islam M. N., Das S. R., Emin M. T., Wei M., Sun L., Westphalen K., Rowlands D. J., Quadri S. K., Bhattacharya S., Bhattacharya J. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Journal of Natural Medicines, 2012, vol. 18, no. 5, pp. 759–765. https://doi.org/10.1038/nm.2736

23. De Becker A., Riet I. V. Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy? World Journal of Stem Cells, 2016, vol. 8, no. 3, pp. 73–87. https://doi.org/10.4252/wjsc.v8.i3.73

24. Giacomini Ch., Granéli C., Hicks R., Dazzi F. The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair. Cellular and Molecular Immunology, 2023, vol. 20, no. 6, pp. 570–582. https://doi.org/10.1038/s41423-023-01018-9

25. de Witte S. F. H., Luk F., Sierra Parraga J. M., Gargesha M., Merino A., Korevaar S. S. [et al.]. Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells. Stem Cells, 2018, vol. 36, no. 4, pp. 602–615. https://doi.org/10.1002/stem.2779


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For citations:


Chуzhуk V.A., Sialitski М.М., Ponomarev V.V. Efficacy and safety of primary and repeated therapy courses of Parkinson’s disease with autologous mesenchymal stromal cells in the long-term period. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2024;21(1):68-78. (In Russ.) https://doi.org/10.29235/1814-6023-2024-21-1-68-78

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ISSN 1814-6023 (Print)
ISSN 2524-2350 (Online)