Tackling prion diseases: a review of the patent landscape

ABSTRACT

Introduction: Prion diseases are a class of rare and fatal neurodegenerative diseases for which no cure is currently available. They are characterized by conformational conversion of cellular prion protein (PrP^C) into the disease-associated ‘scrapie’ isoform (PrP^Sc). Under an etiological point of view, prion diseases can be divided into acquired, genetic, and idiopathic form, the latter of which are the most frequent.

Areas covered: Therapeutic approaches targeting prion diseases are based on the use of chemical and nature-based compounds, targeting either PrP^C or PrP^Sc or other putative player in pathogenic mechanism. Other proposed anti-prion treatments include passive and active immunization strategies, peptides, aptamers, and PrP^C-directed RNA interference techniques. The treatment efficacy has been mainly assessed in cell lines or animal models of the disease testing their ability to reduce prion accumulation.

Expert opinion: The assessed strategies focussing on the identification of an efficient anti-prion therapy faced various issues, which go from permeation of the blood brain barrier to immunological tolerance of the host. Indeed, the use of combinatory approaches, which could boost a synergistic anti-prion effect and lower the potential side effects of single treatments and may represent an extreme powerful and feasible way to tackle prion disease.

KEYWORDS:

• Prion disease
• small molecules
• non-PrP-targeted strategies
• antibodies
• aptamers
• RNA interference

Article highlights

• Prion diseases are fatal debilitating disorders of nervous system for which no treatment has been yet identified.

• Different compounds, targeting either PrP^C or PrP^Sc, have been proposed as putative anti-prion agents, the majority of which demonstrated an efficient in vitro and in vivo ability to halt prion replication.

• Passive or active immunization strategies can be used either as prophylaxis or post-exposure therapy.

• PrP-directed RNA-interference approaches, via a reduction of the pathological conversion substrate level, offer an alternative way to hamper prion propagation.

• Synergistic anti-prion effect could be obtained through the combination of different tested treatments.

Declaration of interest

G Legname possesses several patents in his name, two of which have been cited in the manuscript because they are part of the literature concerning the topic discussed. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Intramural SISSA funding.