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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes

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Therapeutic interventions ameliorating prion disease.

Marcus W Brazier¹, Vanessa A Wall, Barry W Brazier

¹Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia. brazier@unimelb.edu.au

Expert Review of Anti-Infective Therapy

|July 23, 2009

Summary

Effective treatments for prion diseases are urgently needed. This review examines therapeutic strategies in animal models and human trials, focusing on targeting prion replication and other pathways.

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Protein Misfolding Cyclic Amplification of Prions

Protein Misfolding Cyclic Amplification of Prions

Published on: November 7, 2012

Area of Science:

Neuroscience
Infectious Diseases
Biochemistry

Background:

Prion diseases, including Creutzfeldt-Jakob disease, are fatal neurodegenerative disorders.
Effective treatments for prion diseases remain a significant unmet medical need.
Current therapeutic strategies primarily focus on inhibiting prion replication.

Purpose of the Study:

To review therapeutic strategies for prion diseases in animal models.
To provide an overview of completed human treatment trials.
To analyze treatment efficacy based on timing and mechanism of action.

Main Methods:

Inclusion of in vivo studies in animal models of prion disease.
Dichotomization of studies by treatment introduction time relative to inoculation.
Categorization of studies by principal mechanism of action.
Overview of selected completed human clinical trials.

Main Results:

Most treatments aim to inhibit the conversion of cellular prion protein (PrP(c)) to scrapie prion protein (PrP(sc)).
Alternative strategies include substrate depletion and effector pathway abrogation.
Translational application to human disease is limited by experimental design.
Treatments initiated early in experimental animals show problematic benefits.

Conclusions:

Developing effective prion disease treatments is challenging.
Early intervention in animal models does not reliably predict human efficacy.
Further research is needed to overcome translational barriers for prion disease therapies.