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

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Published on: July 23, 2016

Developing Therapeutics for PrP Prion Diseases.

Kurt Giles^1,2, Steven H Olson^1,2, Stanley B Prusiner^1,2,3

¹Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94143.

Cold Spring Harbor Perspectives in Medicine

|January 19, 2017

Summary

This summary is machine-generated.

New prion disease therapeutics show promise, doubling mouse survival. While effective treatments for human prion diseases remain elusive, recent advances offer hope for neurodegenerative disease therapies.

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Area of Science:

Neuroscience
Drug Discovery
Prion Biology

Background:

Prion diseases, such as Creutzfeldt-Jakob disease, are fatal neurodegenerative disorders with no effective treatments.
Over 30 years of research has yielded limited success in developing therapeutic agents.

Purpose of the Study:

To review the history and recent progress in the development of antiprion therapeutics.
To highlight advances in drug discovery for prion diseases, focusing on animal model validation.

Main Methods:

Utilizing high-throughput screening, medicinal chemistry, and pharmacokinetic optimization.
Employing the PrP prion inoculation paradigm as a robust assay for therapeutic efficacy testing.
Screening compounds in cells infected with mouse-passaged PrP prions.

Main Results:

Several orally available compounds have been identified that significantly extend the survival of prion-infected mice (doubling or tripling survival).
A dozen compounds have demonstrated meaningful survival extension in animal models.
No compounds have yet shown efficacy against human prion diseases.

Conclusions:

Recent advances in drug discovery offer hope for developing effective prion disease therapeutics.
The development of antiprion therapeutics is crucial, given the analogous prion mechanisms in common neurodegenerative diseases like Alzheimer's and Parkinson's.