Open AccessEmergence of prions selectively resistant to combination drug therapy
Author(s) -
Cassandra M. Burke,
Kenneth M. K. Mark,
Judit Kun,
Kathryn S. Beauchemin,
Surachai Supattapone
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008581
Subject(s) - combination therapy , scrapie , drug , pathogen , virology , drug resistance , regimen , medicine , infectious agent , pharmacology , biology , immunology , prion protein , microbiology and biotechnology , disease
Prions are unorthodox infectious agents that replicate by templating misfolded conformations of a host-encoded glycoprotein, collectively termed PrP Sc . 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.