從治療到禁藥：基因與細胞禁藥對運動員的影響

From therapy to doping: Effects of gene and cell doping on athletes

10.6223/qcpe.201912_33(4).0004

許宏志(Hung-Chih Hsu)；方世華(Shih-Hua Fang)

運動表現 ； 基因治療 ； 細胞治療 ； 運動員生物護照 ； exercise performance ； gene therapy ； cell therapy ； athlete biological passport

中華體育季刊

33卷4期（2019 / 12 / 01）

243 - 250

繁體中文

過去一般認為只要改變少許運動基因，即可提高運動表現，但最近的一些研究已經推翻了這個想法，因為與高強度運動表現有關的基因為數相當多。世界運動禁藥管制組織於2019年公布的禁用方法，新增細胞禁藥的項目。過去研究顯示以間質幹細胞作為軟骨細胞來源，可用於治療軟骨、肌腱或骨頭損傷。反觀國內，衛生福利部於2018年通過開放6項細胞治療技術，因此，運動員應注意的是，受傷後如須要細胞治療，應先申請治療用途豁免審查以取得核准。為了防止基因與細胞治療被不守法的運動員濫用，許多國際單項運動組織已建立運動員生物護照，長期追蹤紀錄選手之血液及類固醇兩方面的數值變化，應可有效掌握違法的方法物質的使用。本文主要介紹利用基因及細胞治療以改善生理功能的策略，同時討論運動員在醫療權益以及與禁用方法之間的界線。

It has been recognized that changing few genes can improve exercise performance. However, recent researches had subverted this idea because there were so many genes related to high intensity exercise performance. In 2019, World Anti-doping Agency announced a new method: Cell therapy in the banned methods. Previous studies showed that using mesenchymal stem cells as a source of chondrocytes can be used to treat cartilage, tendon or bone damage. Recently, the Ministry of Health and Welfare (ROC) approved six cell therapy technologies in 2018. Therefore, athletes should be aware that if there is a need for cell therapy after injury, it is better to apply for therapeutic purpose and hopefully waived from review. To prevent gene and cell therapy from being abused by unruly athletes, many international individual sport organizations has established athlete biological passport. Long-term tracking of the changes in the haematological and steroidal records of players should be able to effectively grasp the use of illegal methods and substances. This article focuses on strategies including genes and cell therapy for improving the physiological functions, and discusses the boundaries between athletes' medical rights and the banned methods.

1. 方世華(2014)。從基因治療到基因禁藥。運動教練科學，35，1-16。
   連結：
2. Brittberg, M.,Lindahl, A.,Nilsson, A.,Ohlsson, C.,Isaksson, O.,Peterson, L.(1994).Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.The New England Journal of Medicine,331(14),889-895.
3. Bryant, L. M.,Christopher, D. M.,Giles, A. R.,Hinderer, C.,Rodriguez, J. L.,Smith, J. B.,Wilson, J. M.(2013).Lessons learned from the clinical development and market authorization of Glybera.Human Gene Therapy Clinical Development,24(2),55-64.
4. Connor, J.,Woolf, J.,Mazanov, J.(2013).Would they dope? Revisiting the goldman dilemma.British Journal of Sports Medicine,47(11),697-700.
5. Davies, R. L.,Kuiper, N. J.(2019).Regenerative medicine: A review of the evolution of autologous chondrocyte implantation (ACI) therapy.Bioengineering,6(1),22.
6. de la Garza-Rodea, A. S.,van der Velde-van Dijke, I.,Boersma, H.,Goncalves, M. A.,van Bekkum, D. W.,de Vries, A. A.,Knaan-Shanzer, S.(2012).Myogenic properties of human mesenchymal stem cells derived from three different sources.Cell Transplantion,21(1),153-173.
7. Ehlert, T.,Simon, P.,Moser, D. A.(2013).Epigenetics in sports.Sports Medicine,43(2),93-110.
8. Friedmann, T.,Koss, J. O.(2001).Gene transfer and athletics-An impending problem.Molecular Therapy,3(6),819-820.
9. Goodwin, S.,McPherson, J. D.,McCombie, W. R.(2016).Coming of age: Ten years of next-generation sequencing technologies.Nature Reviews Genetics,17(6),333-351.
10. Holzinger, A.,Barden, M.,Abken, H.(2016).The growing world of CAR T cell trials: A systematic review.Cancer Immunology Immunotherapy,65(12),1433-1450.
11. Locke, A. E.,Kahali, B.,Berndt, S. I.,Justice, A. E.,Pers, T. H.,Day, F. R.,Speliotes, E. K.(2015).Genetic studies of body mass index yield new insights for obesity biology.Nature,518(7538),197-206.
12. Mattsson, C. M.,Wheeler, M. T.,Waggott, D.,Caleshu, C.,Ashley, E. A.(2016).Sports genetics moving forward: Lessons learned from medical research.Physiological Genomics,48(3),175-182.
13. Mendell, J. R.,Sahenk, Z.,Malik, V.,Gomez, A. M.,Flanigan, K. M.,Lowes, L. P.,Kaspar, B. K.(2015).A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy.Molecular Therapy,23(1),192-201.
14. Minas, T.(2011).A primer in cartilage repair and joint preservation of the knee e-Book: Expert consult.Elsevier Health Sciences.
15. Mobasheri, A.,Kalamegam, G.,Musumeci, G.,Batt, M. E.(2014).Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions.Maturitas,78(3),188-198.
16. Montgomery, H. E.,Marshall, R.,Hemingway, H.,Myerson, S.,Clarkson, P.,Dollery, C.,Humphries, S. E.(1998).Human gene for physical performance.Nature,393(6682),221-222.
17. Mulcahy, L. A.,Pink, R. C.,Carter, D. R.(2014).Routes and mechanisms of extracellular vesicle uptake.Journal of Extracellular Vesicles,3,24641.
18. Mullard, A.(2016).EMA greenlights second gene therapy.Nature Reviews. Drug Discovery,15(5),299.
19. Neuberger, E. W. I.,Simon, P.(2017).Gene and cell doping: The new frontier-beyond myth or reality.Medicine and Sport Science,62,91-106.
20. Osborne, H.,Anderson, L.,Burt, P.,Young, M.,Gerrard, D.(2016).Australasian College of Sports Physicians-position statement: The place of mesenchymal stem/stromal cell therapies in sport and exercise medicine.British Journal of Sports Medicine,50(20),1237-1244.
21. Pas, H.,Moen, M. H.,Haisma, H. J.,Winters, M.(2017).No evidence for the use of stem cell therapy for tendon disorders: A systematic review.British Journal of Sports Medicine,51(13),996-1002.
22. Pitsiladis, Y. P.,Durussel, J.,Rabin, O.(2014).An integrative 'omics' solution to the detection of recombinant human erythropoietin and blood doping.British Journal of Sports Medicine,48(10),856-861.
23. Pittenger, M. F.,Mackay, A. M.,Beck, S. C.,Jaiswal, R. K.,Douglas, R.,Mosca, J. D.,Marshak, D. R.(1999).Multilineage potential of adult human mesenchymal stem cells.Science,284(5411),143-147.
24. Rahim, S.,Rahim, F.,Shirbandi, K.,Haghighi, B. B.,Arjmand, B.(2018).Sports injuries: Diagnosis, prevention, stem cell therapy, and medical sport strategy.Advances in Experimental and Biology,New York:
25. Rankinen, T.,Fuku, N.,Wolfarth, B.,Wang, G.,Sarzynski, M. A.,Alexeev, D. G.,Bouchard, C.(2016).No evidence of a common DNA variant profile specific to world class endurance athletes.PLoS One,11(1),0147330.
26. Robinson, N.,Saugy, M.,Vernec, A.,Pierre-Edouard, S.(2011).The athlete biological passport: An effective tool in the fight against doping.Clinical Chemistry,57(6),830-832.
27. Sottas, P. E.,Robinson, N.,Rabin, O.,Saugy, M.(2011).The athlete biological passport.Clinical Chemistry,57(7),969-976.
28. Thompson, H.(2012).Performance enhancement: Superhuman athletes.Nature,487(7407),287-289.
29. Trounson, A.,McDonald, C.(2015).Stem cell therapies in clinical trials: Progress and challenges.Cell Stem Cell,17(1),11-22.
30. Uccelli, A.,Moretta, L.,Pistoia, V.(2008).Mesenchymal stem cells in health and disease.Nature Reviews. Immunology,8(9),726.
31. Valadi, H.,Ekstrom, K.,Bossios, A.,Sjostrand, M.,Lee, J. J.,Lotvall, J. O.(2007).Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.Nature Cell Biology,9(6),654-659.
32. Varlet-Marie, E.,Audran, M.,Ashenden, M.,Sicart, M. T.,Piquemal, D.(2009).Modification of gene expression: Help to detect doping with erythropoiesis-stimulating agents.American Journal of Hematology,84(11),755-759.
33. Veritas Genetics. (2015, Sep 29). Veritas genetics breaks $1,000 whole genome barrier. Retrieved from https://futurism.com/veritas-genetics-and-george-church-break-the-1000-whole-genome-barrier
34. Veritas Genetics. (2016, Mar 3). Veritas genetics launches $999 whole genome and sets new standard for genetic testing. Retrieved from https://www.prnewswire.com/news-releases/veritas-genetics-launches-999-whole-genome-and-sets-new-standard-for-genetic-testing-300230258.html
35. Wang, J.,Sun, X.,Zhao, J.,Yang, Y.,Cai, X.,Xu, J.,Cao, P.(2017).Exosomes: A novel strategy for treatment and prevention of diseases.Frontiers Pharmacology,8,300-327.
36. Wood, A. R.,Esko, T.,Yang, J.,Vedantam, S.,Pers, T. H.,Gustafsson, S.,Frayling, T. M.(2014).Defining the role of common variation in the genomic and biological architecture of adult human height.Nature Genetics,46(11),1173-1186.
37. World Anti-Doping Agency. (2019, Jan 1). WADA publishes 2019 prohibited list. Retrieved from https://www.wada-World Anti-Doping Agencyama.org/sites/default/files/wada_2019_english_prohibited_list.pdf
38. World Health Organization. (2017, Feb 21). Haematopoietic Stem Cell Transplantation HSCtx. Geneva. Retrieved from http://www.who.int/transplantation/hsctx/en/
39. Xu, L.,Li, G.(2014).Circulating mesenchymal stem cells and their clinical implications.Journal of Orthopaedic Translation,2(1),1-7.
40. Yamamoto, S.,Azuma, E.,Muramatsu, M.,Hamashima, T.,Ishii, Y.,Sasahara, M.(2016).Significance of extracellular vesicles: Pathobiological roles in disease.Cell Structure and Function,41(2),137-143.
41. Yong, S. B.,Chung, J. Y.,Song, Y.,Kim, Y. H.(2018).Recent challenges and advances in genetically-engineered cell therapy.Journal of Pharmaceutical Investigation,48(2),199-208.
42. Zorzoli, M.,Pipe, A.,Garnier, P. Y.,Vouillamoz, M.,Dvorak, J.(2014).Practical experience with the implementation of an athlete's biological profile in athletics, cycling, football and swimming.British Journal of Sports Medicine,48(10),862-866.

1. 孫佳婷(2021)。基因科技／基因禁藥研究：臺灣運動領域之認識架構。運動教練科學，61，41-51。