COMPARATIVE ANALYSIS OF METHODS OF MITOCHONDRIAL REPLACEMENT THERAPY

DOI: https://doi.org/10.29296/24999490-2019-04-03

A.I. Glukhov(1, 2), A.M. Isagadzhiev(1) 1-I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya st., 8, Moscow, 119991, Russian Federation; 2-M.V. Lomonosov Moscow State University, Leninskie Gory, 1–12, Moscow, 119234, Russian Federation E-mail: [email protected]

Mitochondrial diseases are a group of inherited diseases characterized by the presence of defects in the mitochondrial mechanism of the patient. The distinguishing feature of such diseases is in transferring it via the maternal line to all the offspring. Various methods of mitochondrial replacement therapy are developed for the treatment of such diseases. Mitochondrial replacement therapy is a procedure which is used for the prevention of transferring such diseases via the maternal line to all descendants. There are several methods of this therapy. They are the following: pronuclear transfer, spindle transfer, polar body transfer 1 and 2. In this article, there are described modern used methods of mitochondrial replacement therapy. We should like to mention all the aspects of carrying out these procedures as well as complications and key features which must be taken into consideration when realizing them are also explained. We assessed the efficacy of these methods by comparing the data obtained by other researchers in the last 10 years. Having done such work we make a conclusion the most effective method of mitochondrial replacement therapy to be the polar body transfer 1. Besides it, we have revealed the spindle transfer to be also promising in spite of less prominent experimental results.
Keywords: 
mitochondria, heteroplasmy, mitochondrial diseases, mitochondrial replacement therapy

Список литературы: 
  1. Mossman J.A., Tross J.G., Li N., Wu Z., Rand D.M. Mitochondrial-Nuclear Interactions Mediate Sex-Specific Transcriptional Profiles in Drosophila. Genetics. 2016; 204 (2): 613–30.
  2. Tachibana M., Sparman M., Sritanaudomchai1 H., Ma H., Clepper L.,Woodward J., Li Y., Ramsey C., Kolotushkina O., Mitalipov S. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature. 2009; 461 (7262): 367–72.
  3. Ma H., Folmes C.D., Wu J., Morey R., Mora-Castilla S., Ocampo A., Ma L., Poulton J., Wang X., Ahmed R., Kang E., Lee Y., Hayama T., Li Y., Van Dyken C., Gutierrez N.M., Tippner-Hedges R., Koski A., Mitalipov N., Amato P., Wolf D.P., Huang T., Terzic A., Laurent L.C., Izpisua Belmonte J.C., Mitalipov S. Metabolic rescue in pluripotent cells from patients with mtDNA disease. Nature. 2015; 524 (7564): 234–8.
  4. Tachibana M., Amato P., Sparman M., Woodward J., Melguizo Sanchis D., Ma H., Marti Gutierrez N., Tippner-Hedges R., Kang E., Lee H., Ramsey C., Masterson K., Battaglia D., Lee D., Wu D., Jensen J., Patton P., Gokhale S., Stouffer R., Mitalipov S. Towards germline gene therapy of inherited mitochondrial diseases. Nature. 2013; 493 (7434): 627–31.
  5. Zhang J., Liu H., Luo S., Lu Z., Chávez-Badiola A., Liu Z., Yang M., Merhi Z., Silber SJ., Munné S., Konstantinidis M., Wells D., Tang JJ., Huang T. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod. Biomed. Online. 2017; 34 (4): 361–8.
  6. Richardson J., Irving L., Hyslop L.A., Choudhary M., Murdoch A., Turnbull D.M., Herbert M. Concise reviews: Assisted reproductive technologies to prevent transmission of mitochondrial DNA disease. Stem Cells. 2015; 33 (3): 639–45.
  7. Gorman G.S., Schaefer A.M., Ng Y., Gomez N., Blakely E.L., Alston C.L., Feeney C., Horvath R., Yu‐Wai‐Man P., Chinnery P.F., Taylor R.W., Turnbull D.M., McFarland R. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015; 77 (5): 753–9.
  8. Kang E., Wu J., Gutierrez N.M., Koski A., Tippner-Hedges R., Agaronyan K., Platero-Luengo A., Martinez-Redondo P., Ma H., Lee Y., Hayama T., Van Dyken C., Wang X., Luo S., Ahmed R., Li Y., Ji D., Kayali R., Cinnioglu C., Olson S., Jensen J., Battaglia D., Lee D., Wu D., Huang T., Wolf DP., Temiakov D., Belmonte J.C., Amato P., Mitalipov S. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature. 2016; 540 (7632): 270–5.
  9. Rishishwar L., Jordan I.K. Implications of human evolution and admixture for mitochondrial replacement therapy. BMC Genomics. 2017; 18 (1): 140.
  10. Hyslop L.A., Blakeley P., Craven L., Richardson J., Norah M.E. Fogarty, Fragouli E., Lamb M., Wamaitha S.E., Prathalingam N., Zhang Q., O’Keefe H.,Takeda Y., Arizzi L., Alfarawati S., Tuppen H.A, Irving L., Kalleas D., Choudhary M., Wells D., Murdoch A.P, Turnbull D.M, Niakan K.K., Herbert M.. Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease. Nature. 2016; 534 (7607): 383–6.
  11. Zhang J., Zhuang G., Zeng Y., Grifo J., Acosta C., Shu Y., Liu H. Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF. Reprod. Biomed. Online. 2016; 33 (4): 529–33.
  12. Reznichenko A.S., Huyser C., Pepper M.S. Mitochondrial transfer: Implications for assisted reproductive technologies. Appl Transl Genom. 2016; 11: 40–7.
  13. Neupane J., Vandewoestyne M., Ghimire S., Lu Y., Qian C., Van Coster R., Gerris J., Deroo T., Deforce D., De Sutter P., Heindryckx B. Assessment of nuclear transfer techniques to prevent the transmission of heritable mitochondrial disorders without compromising embryonic development competence in mice. Mitochondrion. 2014; 18: 27–33.
  14. Paull D., Emmanuele V., Weiss K.A., Treff N., Stewart L., Hua H., Zimmer M., Kahler D.J., Goland R.S., Noggle S.A., Prosser R., Hirano M., Sauer M.V., Egli D. Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants. Nature. 2013; 493 (7434): 632–7.
  15. Ma H., O’Neil R.C., Marti Gutierrez N., Hariharan M., Zhang Z.Z., He Y., Cinnioglu C., Kayali R., Kang E., Lee Y., Hayama T., Koski A., Nery J., Castanon R., Tippner-Hedges R., Ahmed R., Van Dyken C., Li Y., Olson S., Battaglia D., Lee D.M., Wu D.H., Amato P., Wolf D.P., Ecker J.R., Mitalipov S. Functional Human Oocytes Generated by Transfer of Polar Body Genomes. Cell Stem Cell. 2017; 20 (1): 112–9.
  16. Wu K., Zhong C., Chen T., Zhang X., Tao W., Zhang J., Li H., Zhao H., Li J., Chen Z.J. Polar bodies are efficient donors for reconstruction of human embryos for potential mitochondrial replacement therapy. Cell Res. 2017; 27 (8): 1069–72.
  17. Yu Y., Dumollard R., Rossbach A., Lai F.A., Swann K. Redistribution of mitochondria leads to bursts of ATP production during spontaneous mouse oocyte maturation. J. Cell. Physiol. 2010; 224 (3): 672–80.
  18. Craven L., Elson J.L., Irving L., Tuppen H.A., Lister L.M., Greggains G.D., Byerley S., Murdoch A.P., Herbert M., Turnbull D. Mitochondrial DNA disease: new options for prevention. Hum. Mol. Genet. 2011; 20 (R2): 168–74.
  19. Engelstad K., Sklerov M., Kriger J., Sanford A., Grier J., Ash D., Egli D., DiMauro S., Thompson J.L., Sauer M.V., Hirano M. Attitudes toward prevention of mtDNA-related diseases through oocyte mitochondrial replacement therapy. Hum Reprod. 2016; 31 (5): 1058–65.
  20. Craven L., Tuppen H.A., Greggains G.D., Harbottle S.J., Murphy J.L., Cree L.M., Murdoch A.P., Chinnery P.F., Taylor R.W., Lightowlers R.N., Herbert M., Turnbull D.M. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature. 2010; 465 (7294): 82–5.
  21. Wang T., Sha H., Ji D., Zhang H.L., Chen D., Cao Y., Zhu J. Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases. Cell. 2014; 157 (7): 1591–604.
  22. Wu K1., Zhong C., Chen T., Zhang X., Tao W., Zhang J., Li H., Zhao H., Li J., Chen Z.J. Polar bodies are efficient donors for reconstruction of human embryos for potential mitochondrial replacement therapy. Cell Res. 2017; 27 (8): 1069–72.