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PLoS One. 2014 Feb 14;9(2):e88797. doi: 10.1371/journal.pone.0088797. eCollection 2014.

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

Author information

1
Institut de Médecine Régénératrice et de Biothérapie (I.M.R.B.), Physiopathologie, diagnostic et thérapie cellulaire des affections neurodégénératives -Institut National de la Santé et de la Recherche Médicale Université Montpellier 1 U1040 Centre Hospitalo-Universitaire de Montpellier, Université Montpellier 1, Montpellier, France ; Institut de Génétique Humaine, Centre National de la Recherche Scientifique- UPR1142, Montpellier, France.
2
Institut de Génétique Humaine, Centre National de la Recherche Scientifique- UPR1142, Montpellier, France.
3
Medesis Pharma SA, Baillargues, France.
4
Institut de Médecine Régénératrice et de Biothérapie (I.M.R.B.), Physiopathologie, diagnostic et thérapie cellulaire des affections neurodégénératives -Institut National de la Santé et de la Recherche Médicale Université Montpellier 1 U1040 Centre Hospitalo-Universitaire de Montpellier, Université Montpellier 1, Montpellier, France.
5
Université Montpellier2, Montpellier, France.

Abstract

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.

PMID:
24551164
PMCID:
PMC3925167
DOI:
10.1371/journal.pone.0088797
[Indexed for MEDLINE]
Free PMC Article

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