Emergence of prions selectively resistant to combination drug therapy.

Autor: Cassandra M Burke, Kenneth M K Mark, Judit Kun, Kathryn S Beauchemin, Surachai Supattapone
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS Pathogens, Vol 16, Iss 5, p e1008581 (2020)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1008581
Popis: 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.
Databáze: Directory of Open Access Journals
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