Terapi sel punca pada penyakit Parkinson
Sili Putri Adisti(1*), Subagya Subagya(2), Samekto Wibowo(3)
(1) KSM Saraf, RSUD Wonosari Gunungkidul, Yogyakarta
(2) Departemen Neurologi, Fakultas Kedokteran, Kesehatan Masyarakat dan Keperawatan, Universitas Gadjah Mada, Yogyakarta
(3) Departemen Neurologi, Fakultas Kedokteran, Kesehatan Masyarakat dan Keperawatan, Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author
Abstract
Stem cells therapy is one of exciting potential for Parkinson’s disease (PD) treatment because of the superiority for replacing dopamine (DA) neurons degeneration in substantia nigra of middle brain, which causes the motor symptoms and non-motor symptoms of PD. The purpose of this article is to review various theories and current studies about stem cell therapy for PD.
The development of stem cells therapy for PD is quite slow because it has problems related to patient selection, safety, and ethical concerns. So far, there have been no stem cell research for PD publications for phase IV clinical trials according to United States Food and Drug Administration (FDA) . Current researches have only reached phase I-III clinical trials, which some studies are still in the research process and not published yet.
At present, stem cell researchers are still looking for the best method for transplanting stem cells in PD patients. Optimization of stem cell therapy for PD can be done by: 1) choosing the right donor stem cells, 2) inducing and selecting DA neurons appropriately, 3) conducting valid preclinical research, 4) optimizing the host brain environment.
Further studies are needed to answer some crucial questions about the different issues in stem cell therapy. Accordingly, stem cell based therapy for PD also needs more evaluation in both basic and clinical study areas.
ABSTRAK
Terapi sel punca merupakan salah satu terapi potensial untuk penyakit Parkinson dikarenakan keunggulannya dalam menggantikan degenerasi neuron dopamin (DA) di substantia nigra otak tengah yang menyebabkan munculnya gejala motorik dan non-motorik dari penyakit Parkinson. Tujuan penulisan ini adalah untuk mengkaji pustaka berbagai teori dan penelitian terkini tentang terapi sel punca pada penyakit Parkinson.
Pengembangan terapi sel punca untuk penyakit Parkinson cukup terkendala berkaitan dengan masalah pemilihan pasien, keamanan, dan etika. Sejauh ini, belum ada publikasi tentang penelitian sel punca pada penyakit Parkinson yang mencapai tahap IV menurut uji klinis Food and Drug Administration (FDA), Amerika Serikat. Penelitian saat ini baru mencapai tahap I-III, walaupun beberapa penelitian masih dalam berjalan dan belum dipublikasikan.
Saat ini, para peneliti sel punca masih mencari metode terbaik untuk transplantasi sel punca pada pasien penyakit Parkinson. Optimalisasi terapi sel punca pada penyakit Parkinson dapat dilakukan dengan: 1) memilih donor sel punca yang tepat, 2) menginduksi dan memilih neuron DA secara tepat, 3) melakukan uji preklinis yang valid, serta 4) optimalisasi lingkungan otak penerima.
Penelitian lebih lanjut diperlukan untuk menjawab beberapa pertanyaan penting terkait berbagai masalah dalam terapi sel punca. Karenanya, terapi berbasis sel punca pada penyakit Parkinson juga membutuhkan evaluasi yang lebih terintegrasi baik pada penelitian dasar maupun klinis.
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Raaijmakers MHGP. Overview of stem cells. In: Tirnauer JS, editor. UpToDate. USA: UpToDate; 2019.
Pen AE, Jensen UB. Current status of treating neurodegenerative disease with induced pluripotent stem cells. Acta Neurologica Scandinavica. 2017;135(1):57–72.
Khurana V, Tardiff DF, Chung CY, Lindquist S. Toward stem cell-based phenotypic screens for neurodegenerative diseases. Nature Reviews Neurology. 2015;11(6):339–350.
Aaroe AE, Henchcliffe C. Promises and Challenges of MSC- Based Therapies: Parkinson Disease and Parkinsonism. In: A Roadmap to Non-Hematopoietic Stem Cell-based Therapeutics. Elsevier; 2019. page 297–320.
Han F, Baremberg D, Gao J, Duan J, Lu X, Zhang N, et al. Development of stem cell-based therapy for Parkinson’s disease. Translational Neurodegeneration. 2015;4(1):16.
Sethi KD. The impact of levodopa on quality of life in patients with Parkinson disease. The Neurologist. 2010;16(2):76–83.
Vitek JL, Bakay RAE, Freeman A, Evatt M, Green J, McDonald W, et al. Randomized trial of pallidotomy versus medical therapy for Parkinson’s disease. Annals of Neurology. 2003;53(5):558– 569.
Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. The Lancet Neurology. 2009;8(1):67–81.
Yasuhara T, Kameda M, Sasaki T, Tajiri N, Date I. Cell therapy for Parkinson’s disease. Cell Transplantation. 2017;26(9):1551– 1559.
Lindvall O, Gustavii B, Åstedt B, Lindholm T, Rehncrona S, Brundin P, et al. Fetal dopamine-rich mesencephalic grafs in Parkinson’s disease. The Lancet. 1988;332(8626–8627):1483– 1484.
Madrazo I, León V, Torres C, Aguilera MC, Varela G, Alvarez F, et al. Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson’s disease. The New England Journal of Medicine. 1988;318(1):51.
Jankovic J, Tolosa E, editors. Parkinson’s disease & movement disorders. Philadelphia: Wolters Kluwer; 2015. 576 page.
Palmer C, Coronel R, Bernabeu-Zornoza A, Liste I. Therapeutic Application of Stem Cell and Gene Therapy in Parkinson’s Disease. In: Singh S, Joshi N, editors. Pathology, Prevention and Therapeutics of Neurodegenerative Disease. Singapore: Springer Singapore; 2019. page 159–171.
Goldberg NRS, Caesar J, Park A, Sedgh S, Finogenov G, Masliah E, et al. Neural stem cells rescue cognitive and motor dysfunction in a transgenic model of dementia with Lewy bodies through a BDNF-dependent mechanism. Stem Cell Reports. 2015;5(5):791–804.
Marsh SE, Blurton-Jones M. Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support. Neurochemistry International. 2017;106:94–100.
Park S, Kim E, Koh S-E, Maeng S, Lee W, Lim J, et al. Dopaminergic differentiation of neural progenitors derived from placental mesenchymal stem cells in the brains of Parkinson’s disease model rats and alleviation of asymmetric rotational behavior. Brain Research. 2012;1466:158–166.
Park H-J, Shin JY, Lee BR, Kim HO, Lee PH. Mesenchymal stem cells augment neurogenesis in the subventricular zone and enhance differentiation of neural precursor cells into dopaminergic neurons in the substantia nigra of a parkinsonian model. Cell Transplantation. 2012;21(8):1629–1640.
Stemberger S, Jamnig A, Stefanova N, Lepperdinger G, Reindl M, Wenning GK. Mesenchymal stem cells in a transgenic mouse model of multiple system atrophy: immunomodulation and neuroprotection. Schuelke M, editor. PLoS ONE. 2011;6(5):e19808.
Yang D, Zhang Z-J, Oldenburg M, Ayala M, Zhang S-C. Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats. Stem Cells. 2008;26(1):55–63.
Kim J-H, Auerbach JM, Rodríguez-Gómez JA, Velasco I, Gavin D, Lumelsky N, et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature. 2002;418(6893):50–56.
Wernig M, Zhao J-P, Pruszak J, Hedlund E, Fu D, Soldner F, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proceedings of the National Academy of Sciences. 2008;105(15):5856–5861.
Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, et al. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proceedings of the National Academy of Sciences. 2010;107(36):15921–15926.
Mathieu P, Roca V, Gamba C, del Pozo A, Pitossi F. Neuroprotective effects of human umbilical cord mesenchymal stromal cells in an immunocompetent animal model of Parkinson’s disease. Journal of Neuroimmunology. 2012;246(1– 2):43–50.
DOI: https://doi.org/10.22146/bns.v19i3.73904
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