PLoS ONE (Jan 2014)

Systemic delivery of siRNA down regulates brain prion protein and ameliorates neuropathology in prion disorder.

  • Sylvain Lehmann,
  • Aroa Relano-Gines,
  • Sarah Resina,
  • Elsa Brillaud,
  • Danielle Casanova,
  • Charles Vincent,
  • Claire Hamela,
  • Sophie Poupeau,
  • Mathieu Laffont,
  • Audrey Gabelle,
  • Constance Delaby,
  • Maxime Belondrade,
  • Jacques-Damien Arnaud,
  • Maria-Teresa Alvarez,
  • Jean-Claude Maurel,
  • Patrick Maurel,
  • Carole Crozet

DOI
https://doi.org/10.1371/journal.pone.0088797
Journal volume & issue
Vol. 9, no. 2
p. e88797

Abstract

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One of the main challenges for neurodegenerative disorders that are principally incurable is the development of new therapeutic strategies, which raises important medical, scientific and societal issues. Creutzfeldt-Jakob diseases are rare neurodegenerative fatal disorders which today remain incurable. The objective of this study was to evaluate the efficacy of the down-regulation of the prion protein (PrP) expression using siRNA delivered by, a water-in-oil microemulsion, as a therapeutic candidate in a preclinical study. After 12 days rectal mucosa administration of Aonys/PrP-siRNA in mice, we observed a decrease of about 28% of the brain PrP(C) level. The effect of Aonys/PrP-siRNA was then evaluated on prion infected mice. Several mice presented a delay in the incubation and survival time compared to the control groups and a significant impact was observed on astrocyte reaction and neuronal survival in the PrP-siRNA treated groups. These results suggest that a new therapeutic scheme based an innovative delivery system of PrP-siRNA can be envisioned in prion disorders.