Emergence of prions selectively resistant to combination drug therapy


Autoři: Cassandra M. Burke aff001;  Kenneth M. K. Mark aff001;  Judit Kun aff001;  Kathryn S. Beauchemin aff001;  Surachai Supattapone aff001
Působiště autorů: Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America aff001;  Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America aff002
Vyšlo v časopise: Emergence of prions selectively resistant to combination drug therapy. PLoS Pathog 16(5): e32767. doi:10.1371/journal.ppat.1008581
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008581

Souhrn

Prions are unorthodox infectious agents that replicate by templating misfolded conformations of a host-encoded glycoprotein, collectively termed PrPSc. Prion diseases are invariably fatal and currently incurable, but oral drugs that can prolong incubation times in prion-infected mice have been developed. Here, we tested the efficacy of combination therapy with two such drugs, IND24 and Anle138b, in scrapie-infected mice. The results indicate that combination therapy was no more effective than either IND24 or Anle138b monotherapy in prolonging scrapie incubation times. Moreover, combination therapy induced the formation of a new prion strain that is specifically resistant to the combination regimen but susceptible to Anle138b. To our knowledge, this is the first report of a pathogen with specific resistance to combination therapy despite being susceptible to monotherapy. Our findings also suggest that combination therapy may be a less effective strategy for treating prions than conventional pathogens.

Klíčová slova:

Animal prion diseases – Cancer treatment – Combination chemotherapy – Drug therapy – Immunohistochemistry techniques – Mouse models – Prion diseases – Prions


Zdroje

1. Bartz JC. Prion Strain Diversity. Cold Spring Harb Perspect Med. 2016;6(12). doi: 10.1101/cshperspect.a024349 27908925; PubMed Central PMCID: PMC5131755.

2. Giles K, Olson SH, Prusiner SB. Developing Therapeutics for PrP Prion Diseases. Cold Spring Harb Perspect Med. 2017;7(4). doi: 10.1101/cshperspect.a023747 28096242; PubMed Central PMCID: PMC5378016.

3. Forloni G, Artuso V, Roiter I, Morbin M, Tagliavini F. Therapy in prion diseases. Current topics in medicinal chemistry. 2013;13(19):2465–76. Epub 2013/09/26. doi: 10.2174/15680266113136660173 24059336.

4. Supattapone S, Nishina K, Rees JR. Pharmacological approaches to prion research. Biochem Pharmacol. 2002;63(8):1383–8. doi: 10.1016/s0006-2952(02)00874-2 11996878.

5. Li J, Browning S, Mahal SP, Oelschlegel AM, Weissmann C. Darwinian Evolution of Prions in Cell Culture. Science. 2009;327(5967):869–72. doi: 10.1126/science.1183218 20044542.

6. Angers RC, Kang HE, Napier D, Browning S, Seward T, Mathiason C, et al. Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science. 2010;328(5982):1154–8. Epub 2010/05/15. science.1187107 [pii] doi: 10.1126/science.1187107 20466881.

7. Collinge J, Clarke AR. A general model of prion strains and their pathogenicity. Science. 2007;318(5852):930–6. Epub 2007/11/10. 318/5852/930 [pii] doi: 10.1126/science.1138718 17991853.

8. Berry DB, Lu D, Geva M, Watts JC, Bhardwaj S, Oehler A, et al. Drug resistance confounding prion therapeutics. Proc Natl Acad Sci U S A. 2013;110(44):E4160–9. Epub 2013/10/17. doi: 10.1073/pnas.1317164110 24128760; PubMed Central PMCID: PMC3816483.

9. Ghaemmaghami S, Ahn M, Lessard P, Giles K, Legname G, DeArmond SJ, et al. Continuous quinacrine treatment results in the formation of drug-resistant prions. PLoS Pathog. 2009;5(11):e1000673. Epub 2009/12/04. doi: 10.1371/journal.ppat.1000673 19956709; PubMed Central PMCID: PMC2777304.

10. Berry D, Giles K, Oehler A, Bhardwaj S, DeArmond SJ, Prusiner SB. Use of a 2-aminothiazole to Treat Chronic Wasting Disease in Transgenic Mice. The Journal of infectious diseases. 2015;212 Suppl 1:S17–25. Epub 2015/06/28. doi: 10.1093/infdis/jiu656 26116725; PubMed Central PMCID: PMC4551108.

11. Bian J, Kang HE, Telling GC. Quinacrine promotes replication and conformational mutation of chronic wasting disease prions. Proc Natl Acad Sci U S A. 2014;111(16):6028–33. doi: 10.1073/pnas.1322377111 24711410; PubMed Central PMCID: PMC4000840.

12. Mehta KC, Dargad RR, Borade DM, Swami OC. Burden of antibiotic resistance in common infectious diseases: role of antibiotic combination therapy. Journal of clinical and diagnostic research: JCDR. 2014;8(6):ME05–8. Epub 2014/08/15. doi: 10.7860/JCDR/2014/8778.4489 25121020; PubMed Central PMCID: PMC4129256.

13. DeVita VT Jr., Chu E. A history of cancer chemotherapy. Cancer research. 2008;68(21):8643–53. Epub 2008/11/01. doi: 10.1158/0008-5472.CAN-07-6611 18974103.

14. Joshi JM. Tuberculosis chemotherapy in the 21 century: Back to the basics. Lung India: official organ of Indian Chest Society. 2011;28(3):193–200. Epub 2011/09/03. doi: 10.4103/0970-2113.83977 21886955; PubMed Central PMCID: PMC3162758.

15. DeVita VT Jr., Lewis BJ, Rozencweig M, Muggia FM. The chemotherapy of Hodgkin's disease: past experiences and future directions. Cancer. 1978;42(2 Suppl):979–90. Epub 1978/08/01. doi: 10.1002/1097-0142(197808)42:2+<979::aid-cncr2820420721>3.0.co;2-s 356960.

16. Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F, et al. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease. Acta Neuropathol. 2013;125(6):795–813. Epub 2013/04/23. doi: 10.1007/s00401-013-1114-9 23604588; PubMed Central PMCID: PMC3661926.

17. Makarava N, Baskakov IV. Genesis of tramsmissible protein states via deformed templating. Prion. 2012;6(3):252–5. Epub 2012/05/09. doi: 10.4161/pri.19930 [pii]. 22561163; PubMed Central PMCID: PMC3399541.

18. Abdulrahman BA, Tahir W, Doh-Ura K, Gilch S, Schatzl HM. Combining autophagy stimulators and cellulose ethers for therapy against prion disease. Prion. 2019;13(1):185–96. doi: 10.1080/19336896.2019.1670928 31578923; PubMed Central PMCID: PMC6779372.

19. Piro JR, Harris BT, Nishina K, Soto C, Morales R, Rees JR, et al. Prion protein glycosylation is not required for strain-specific neurotropism. J Virol. 2009;83(11):5321–8. doi: 10.1128/JVI.02502-08 19297485.

20. Deleault NR, Piro JR, Walsh DJ, Wang F, Ma J, Geoghegan JC, et al. Isolation of phosphatidylethanolamine as a solitary cofactor for prion formation in the absence of nucleic acids. Proc Natl Acad Sci U S A. 2012;109(22):8546–51. Epub 2012/05/16. 1204498109 [pii] doi: 10.1073/pnas.1204498109 22586108.

21. Orru CD, Hughson AG, Groveman BR, Campbell KJ, Anson KJ, Manca M, et al. Factors That Improve RT-QuIC Detection of Prion Seeding Activity. Viruses. 2016;8(5). doi: 10.3390/v8050140 27223300; PubMed Central PMCID: PMC4885095.

22. Arosio P, Knowles TP, Linse S. On the lag phase in amyloid fibril formation. Phys Chem Chem Phys. 2015;17(12):7606–18. doi: 10.1039/c4cp05563b 25719972; PubMed Central PMCID: PMC4498454.

23. McLean AR, Bostock CJ. Scrapie infections initiated at varying doses: an analysis of 117 titration experiments. Philos Trans R Soc Lond B Biol Sci. 2000;355(1400):1043–50. doi: 10.1098/rstb.2000.0641 11186305.

24. Kulkarni RV, Slepoy A, Singh RR, Cox DL, Pazmandi F. Theoretical modeling of prion disease incubation. Biophys J. 2003;85(2):707–18. doi: 10.1016/S0006-3495(03)74514-7 12885622; PubMed Central PMCID: PMC1303196.

25. Hortschansky P, Schroeckh V, Christopeit T, Zandomeneghi G, Fandrich M. The aggregation kinetics of Alzheimer's beta-amyloid peptide is controlled by stochastic nucleation. Protein Sci. 2005;14(7):1753–9. doi: 10.1110/ps.041266605 15937275; PubMed Central PMCID: PMC2253354.

26. Koppen J, Schulze A, Machner L, Wermann M, Eichentopf R, Guthardt M, et al. Amyloid-Beta Peptides Trigger Aggregation of Alpha-Synuclein In Vitro. Molecules. 2020;25(3). doi: 10.3390/molecules25030580 32013170; PubMed Central PMCID: PMC7037551.


Článek vyšel v časopise

PLOS Pathogens


2020 Číslo 5

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×