EUropean Research initiative to develop Imaging Probes for early In-vivoDiagnosis and Evaluation of response to therapeutic Substances

 

Acronym: EURIPIDES
Title: EUropean Research initiative to develop Imaging Probes for early In-vivoDiagnosis and Evaluation of response to therapeutic Substances
Status: Active
Funding Organization: European Union
NCSR D

Role:

Participant
Leader in charge: A. Varvarigou
Start Date: 21/11/2007
Duration: 36 months
Project

Website:

 
www.euripides-europe.com 
Summary EURIPIDES aims to develop in-vivo imaging biomarker(s) of multidrug transporter function as a generic tool for the prediction, diagnosis, monitoring and prognosis of major CNS diseases, as well as to provide support and guidance for therapeutic interventions. The project is in great part focused in facing drug resistance to antiepileptic drugs.

Resistance to drug treatment is an important hurdle in the therapy of many diseases of the central nervous system (CNS). Consequently, there is a pressing need to develop new and more effective treatment strategies, taking into consideration mainly that inadequate access of CNS drugs to their targets across the blood-brain barrier (BBB) is due to the overexpression or overactivity of multdrug transporters. These multidrug transporters, of which P-glycoprotein (P-gp) is the most-widely studied, are found in and contribute to the normal BBB, and as efflux transporters, actively transport substrates (including multiple CNS drugs) against concentration gradients from the brain to blood and cerebrospinal fluid. This hampers the build up of adequate tissue levels of these drugs in the brain, greatly limiting their therapeutic efficacy. As such, the "transporter hypothesis" of drug resistance is applicable to a broad range of CNS drugs and patients with a variety of CNS diseases who critically depend on these drugs. Efflux transporters may also influence brain elimination of A?, the hallmark of Alzheimer’s disease (AD). Within EURIPIDES the contribution of multidrug transporters to impaired brain uptake of drugs for the prediction of therapeutic responses will be determined. Demonstration of overexpression or underactivity of transporter function is essential and necessary. An in-vivo imaging biomarker of multidrug transporter function is essential for identifying altered transporter activity in individual patient. Such a biomarker will provide the means for predicting treatment response or early diagnosis.