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


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


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PLOS Pathogens

2020 Číslo 5
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