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Yamagishi Y, Kudo T, Oyumi M, et al. Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease. Pharm Res. 2021;38(8):1335-1344doi: 10.1007/s11095-021-03090-0.
Yamagishi, Y., Kudo, T., Oyumi, M., Sakamoto, Y., Takahashi, K., Akashi, T., Kobayashi, S., Kawakami, T., Goda, H., Sato, Y., Mimaki, M., Kodama, H., Munakata, M., Makino, K., Takahashi, H., Fukami, T., & Ito, K. (2021). Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease. Pharmaceutical research, 38(8), 1335-1344. https://doi.org/10.1007/s11095-021-03090-0
Yamagishi, Yoshiaki, et al. "Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease." Pharmaceutical research vol. 38,8 (2021): 1335-1344. doi: https://doi.org/10.1007/s11095-021-03090-0
Yamagishi Y, Kudo T, Oyumi M, Sakamoto Y, Takahashi K, Akashi T, Kobayashi S, Kawakami T, Goda H, Sato Y, Mimaki M, Kodama H, Munakata M, Makino K, Takahashi H, Fukami T, Ito K. Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease. Pharm Res. 2021 Aug;38(8):1335-1344. doi: 10.1007/s11095-021-03090-0. Epub 2021 Aug 17. PMID: 34403032.
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Pharm Res. 2021 Aug;38(8):1335-1344. doi: 10.1007/s11095-021-03090-0. Epub 2021 Aug 17.

Pharmacokinetics of CuGTSM, a Novel Drug Candidate, in a Mouse Model of Menkes Disease.

Pharmaceutical research

Yoshiaki Yamagishi, Toshiyuki Kudo, Masafumi Oyumi, Yusuke Sakamoto, Kazuki Takahashi, Taiki Akashi, Shohei Kobayashi, Takeaki Kawakami, Hitomi Goda, Yasuhiro Sato, Masakazu Mimaki, Hiroko Kodama, Mitsutoshi Munakata, Kosho Makino, Hideyo Takahashi, Toshiro Fukami, Kiyomi Ito

Affiliations

  1. Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
  2. Department of Molecular Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
  3. Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan.
  4. Health and Dietetics, Teikyo Heisei University, Graduate School of Health Sciences, Tokyo, Japan.
  5. Department of Pediatrics, Tohoku University School of Medicine, Miyagi, Japan.
  6. Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
  7. Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan. [email protected].

PMID: 34403032 DOI: 10.1007/s11095-021-03090-0

Abstract

PURPOSE: Menkes disease is a rare hereditary disease in which systemic deficiency of copper due to mutation of the ATP7A gene causes severe neurodegenerative disorders. The present parenteral drugs have limited efficacy, so there is a need for an efficacious drug that can be administered orally. This study focused on glyoxal-bis (N(4)-methylthiosemicarbazonato)-copper(II (CuGTSM), which has shown efficacy in macular mice, a murine model of Menkes disease, and examined its pharmacokinetics. In addition, nanosized CuGTSM (nCuGTSM) was prepared, and the effects of nanosizing on CuGTSM pharmacokinetics were investigated.

METHODS: CuGTSM or nCuGTSM (10 mg/kg) was administered orally to male macular mice or C3H/HeNCrl mice (control), and plasma was obtained by serial blood sampling. Plasma concentrations of CuGTSM and GTSM were measured by LC-MS/MS and pharmacokinetic parameters were calculated.

RESULTS: When CuGTSM was administered orally, CuGTSM and GTSM were both detected in the plasma of both mouse strains. When nCuGTSM was administered, the C

CONCLUSION: Absorption of orally administered CuGTSM was confirmed in macular mice, and the nano-formulation improved the absorption and retention of CuGTSM in the body. However, the plasma concentration of CuGTSM was lower in macular mice than in control mice, suggesting easier dissociation of CuGTSM.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords: Copper; CuGTSM; Macular mouse; Menkes disease; Nanosizing

References

  1. Tümer Z, Møller LB. Menkes disease. Eur J Hum Genet. 2010;18:511–8. - PubMed
  2. Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet. 1993;3:7–13. - PubMed
  3. Kodama H, Murata Y. Molecular genetics and pathophysiology of Menkes disease. Pediatr Int. 1999;41:430–35. - PubMed
  4. Chelly J, Tümer Z, Tønnesen T, Petterson A, Ishikawa-Brush Y, Tommerup N, Horn N, Monaco AP. Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein. Nat Genet. 1993;3:14–9. - PubMed
  5. Mercer JF, Livingston J, Hall B, Paynter JA, Begy C, Chandrasekharappa S, et al. Isolation of a partial candidate gene for Menkes disease by positional cloning. Nat Genet. 1993;3:20–5. - PubMed
  6. Kaler SG, Gallo LK, Proud VK, Percy AK, Mark Y, Segal NA, Goldstein DS, Holmes CS, Gahl WA. Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus. Nat Genet. 1994;8:195–202. - PubMed
  7. Tümer Z, Horn N. Menkes disease: recent advances and new aspects. J Med Genet. 1997;34:265–74. - PubMed
  8. Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY. Function and regulation of human copper-transporting ATPases. Physiol Rev. 2007;87:1011–46. - PubMed
  9. Choi BS, Zheng W. Copper transport to the brain by the blood-brain barrier and blood-CSF barrier. Brain Res. 2009;1248:14–21. - PubMed
  10. Sarkar B, Lingertat-Walsh K, Clarke JT. Copper-histidine therapy for Menkes disease. J Pediatr. 1993;123:828–30. - PubMed
  11. Kodama H, Fujisawa C, Bhadhprasit W. Pathology, clinical features and treatments of congenital copper metabolic disorders-focus on neurologic aspects. Brain and Development. 2011;33:243–51. - PubMed
  12. Tanaka K, Kobayashi K, Fujita Y, Fukuhara C, Onosaka S, Min K. Effects of chelators on copper therapy of macular mouse, a model animal of Menkes’ kinky disease. Res Commun Chem Pathol Pharmacol. 1990;69:217–27. - PubMed
  13. Lenartowicz M, Krzeptowski W, Koteja P, Chrzascik K, Møller LB. Prenatal treatment of mosaic mice (Atp7a mo-ms) mouse model for Menkes disease, with copper combined by dimethyldithiocarbamate (DMDTC). PLoS ONE. 2012;7:e40400. - PubMed
  14. Kodama H, Sato E, Gu YH, Shiga K, Fujisawa C, Kozuma T. Effect of copper and diethyldithiocarbamate combination therapy on the macular mouse, an animal model of Menkes disease. J Inherit Metab Dis. 2005;28:971–8. - PubMed
  15. Bhadhprasit W, Kodama H, Fujisawa C, Hiroki T, Ogawa E. Effect of copper and disulfiram combination therapy on the macular mouse, a model of Menkes disease. J Trace Elem Med Biol. 2012;26:105–8. - PubMed
  16. Ogawa E, Kodama H. Effects of disulfiram treatment in patients with Menkes disease and occipital horn syndrome. J Trace Elem Med Biol. 2012;26:102–4. - PubMed
  17. Paterson BM, Donnelly PS. Copper complexes of bis(thiosemicarbazones): from chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals. Chem Soc Rev. 2011;40:3005–18. - PubMed
  18. Yoshii Y, Matsumoto H, Yoshimoto M, Furukawa T, Morokoshi Y, Sogawa C, et al. Controlled administration of penicillamine reduces radiation exposure in critical organs during - PubMed
  19. Matsumoto H, Yoshii Y, Baden A, Kaneko E, Hashimoto H, Suzuki H, et al. Preclinical pharmacokinetic and safety studies of copper-diacetyl-Bis(N4-Methylthiosemicarbazone) (Cu-ATSM): Translational studies for internal radiotherapy. Transl Oncol. 2019;12:1206–12. - PubMed
  20. Crouch PJ, Hung LW, Adlard PA, Cortes M, Lal V, Filiz G, Perez KA, Nurjono M, Caragounis A, du T, Laughton K, Volitakis I, Bush AI, Li QX, Masters CL, Cappai R, Cherny RA, Donnelly PS, White AR, Barnham KJ. Increasing cu bioavailability inhibits Aβ oligomers and tau phosphorylation. Proc Natl Acad Sci U S A. 2009;106:381–6. - PubMed
  21. Speer A, Shrestha TB, Bossmann SH, Basaraba RJ, Harber GJ, Michalek SM, Niederweis M, Kutsch O, Wolschendorf F. Copper-boosting compounds: a novel concept for antimycobacterial drug discovery. Antimicrob Agents Chemother. 2013;57:1089–91. - PubMed
  22. Dehdashti F, Grigsby PW, Lewis JS, Laforest R, Siegel BA, Welch MJ. Assessing tumor hypoxia in cervical cancer by PET with - PubMed
  23. Dietz DW, Dehdashti F, Grigsby PW, Malyapa RS, Myerson RJ, Picus J, Ritter J, Lewis JS, Welch MJ, Siegel BA. Tumor hypoxia detected by positron emission tomography with - PubMed
  24. Lewis JS, Laforest R, Dehdashti F, Grigsby PW, Welch MJ, Siegel BA. An imaging comparison of - PubMed
  25. Munakata M, Kodama H, Fujisawa C, Hiroki T, Kimura K, Watanabe M, Nishikawa M, Tsuchiya S. Copper-trafficking efficacy of copper-pyruvaldehyde bis(N4-methylthiosemicarbazone) on the macular mouse, an animal model of Menkes disease. Pediatr Res. 2012;72:270–6. - PubMed
  26. Munakata M, Kodama H, Tani N, Kimura K, Takahashi H, Maruyama K, Sakamoto Y, Kure S. Menkes disease: Oral administration of glyoxal-bis(N(4)-methylthiosemicarbazonato)-copper(II) rescues the macular mouse. Pediatr Res. 2018;84:770–7. - PubMed
  27. Andres SA, Bajaj K, Vishnosky NS, Peterson MA, Mashuta MS, Buchanan RM, Bates PJ, Grapperhaus CA. Synthesis, characterization, and biological activity of hybrid thiosemicarbazone-alkylthiocarbamate metal complexes. Inorg Chem. 2020;59:4924–35. - PubMed
  28. Torchilin VP. Multifunctional Nanocarriers. Adv Drug Deliv Rev. 2006;58:1532–55. - PubMed
  29. Taghipour YD, Hajialyani M, Naseri R, Hesari M, Mohammadi P, Stefanucci A, et al. Nanoformulations of natural products for management of metabolic syndrome. Int J Nanomedicine. 2019;14:5303–21. - PubMed
  30. Gingras BA, Suprunchuk T, Bayley CH. The preparation of some thiosemicarbazones and their copper complexes part III. Can J Chem. 1902;40:1053–9. - PubMed
  31. Betts HM, Barnard PJ, Bayly SR, Dilworth JR, Gee AD, Holland JP. Controlled axial coordination: solid-phase synthesis and purification of metallo-radiopharmaceuticals. Angew Chem Int Ed. 2008;47:8416–9. - PubMed
  32. Bhattacharjee A, Yang H, Duffy M, Robinson E, Conrad-Antoville A, Lu YW, Capps T, Braiterman L, Wolfgang M, Murphy MP, Yi L, Kaler SG, Lutsenko S, Ralle M. The activity of Menkes disease protein ATP7A is essential for redox balance in mitochondria. J Biol Chem. 2016;291:16644–58. - PubMed

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