Neuroprotection - STAIR-way to the future?

Abstract

Preclinical testing of putative neuroprotective agents for the treatment of acute ischaemic stroke is critical in assessing their therapeutic potential. Guidelines on how preclinical development of neuroprotectants should be performed were lacking until the Stroke Therapy Academic Industry Roundtable (STAIR) published their recommendations based on lessons from previous failed clinical trials of neuroprotective agents. The STAIR recommendations seek to improve the quality of preclinical research and to ensure that the data generated will enable the selection of those agents most suitable for progression from the laboratory into clinical trials. NXY-059 is a novel free-radical trapping neuroprotectant that is being investigated for the treatment of acute ischaemic stroke. Its preclinical development has closely adhered to the stringent STAIR criteria. Data from independent studies using rodent models of transient middle cerebral artery occlusion (tMCAO) and permanent MCAO (pMCAO) show that NXY-059 reduces infarct volume, improves neurological functioning and has an extended therapeutic window (≥4 h) compared with other agents in late-stage clinical development to date. A key difference in its development compared with previous neuroprotectants is that, in accordance with STAIR criteria, its neuroprotective efficacy has been confirmed in large animal models of pMCAO. These studies in marmosets clearly demonstrate that NXY-059 reduces the functional disability arising from cerebral ischaemia. As functional outcome (rather than infarct volume) is the relevant outcome against which stroke drugs are evaluated in clinical trials, this finding is both important and encouraging. NXY-059 is currently being evaluated in Phase III trials. Copyright © 2006 S. Karger AG.