Award details

Intervention in TSE models

Reference	BBS/E/A/00001662
Principal Investigator / Supervisor	Mrs Christine Farquhar
Co-Investigators / Co-Supervisors
Institution	The Roslin Institute
Department	The Roslin Institute Department
Funding type	Research
Value (£)	77,854
Status	Completed
Type	Institute Project
Start date	01/04/2007
End date	31/03/2009
Duration	24 months

Abstract

We have shown in rodents that pentosan polysulphate (PPS) can stop or delay disease, but efficacy is model dependent and effective dose can be associated with adverse effects. Currently PPS is in use on a compassionate basis for clinical vCJD where it appears to delay deterioration. We do not know the size of the at risk, BSE, or vCJD, exposed population. Nothing is known about the pharmacokinetics of PPS in the normal or TSE affected human (or other animal) CNS, and little about long term delivery to the periphery other that perorally. Little is known about the mechanism of action of PPS and its target species. Modification of the molecule, determination of the active site(s), definition of therapeutic target(s) and better delivery systems are required to exploit the potential of this and other drugs. Much of this work will be done in rodent models but a larger animal (sheep) TSE model is required to develop an evidence base for clinical intervention and protocols for clinical assessment. In vitro test systems are not currently predictive of drug effectiveness in vivo. This is a major problem for drug development in many areas of human disease. An understanding of the mechanisms of drug action should permit the development of in vitro systems that are predictive and reduce the use of laboratory animals. That mixing PPS with infected inoculum results in TSE model dependent titre loss suggests physico-chemical differences that could potentially be exploited to increase our understanding of the nature of TSE agents.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	Animal Health, Neuroscience and Behaviour, TSEs (transmissible spongiform encephalopathies)
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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