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 PrPC 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.
Highlights
The development of new therapeutic strategies for neurodegenerative disorders is a major medical, scientific and societal issue
Creutzfeldt-Jakob diseases are rare neurodegenerative fatal disorders which today remain incurable [1]. They belong to prion diseases called transmissible spongiform encephalopathies (TSE)
Many studies performed in the last twenty years have demonstrated the requirement for endogenous prion protein (PrP) expression in the development of a TSE [4], suggesting that inhibiting PrP expression could constitute a good strategy to interfere with prion propagation
Summary
The development of new therapeutic strategies for neurodegenerative disorders is a major medical, scientific and societal issue. Creutzfeldt-Jakob diseases are rare neurodegenerative fatal disorders which today remain incurable [1]. They belong to prion diseases called transmissible spongiform encephalopathies (TSE). TSE are characterized by neurodegeneration, rapid neuronal cell death, vacuolisation and gliosis [1,2] They affect both humans and animals and have a long incubation time before an insidious progression of the disease. The exact nature of the infectious agent responsible for these diseases remains source of debate and is the subject of many studies It appears to be associated with PrPSc, which accumulates in the brain of the host [3].
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