2:00-2:30 Biomarker Qualification and C-Path's Predictive Safety Testing Consortium
William B. Mattes, Ph.D., Director of Toxicology, Safe-Path, The Critical Path Institute
The concern about drug-induced injury and adverse events has resulted in a wide range of approaches to assure the safety of new medicines. These include studies in animals before medicines are even used in humans and monitoring of clinical trials for adverse events. Nonetheless, there is often ambiguity as to implications of certain findings in animals for human safety. On the other hand, new drug candidates that appear to be safe in preclinical tests sometimes show the potential human toxicity in early clinical trials. All in all, the situation points to the need for new and robust assays and markers of drug-induced toxicity that may be reliably applied in both preclinical and clinical studies. The barriers to the development and application of such biomarkers, however, are two-fold: 1) establishment of convincing body of data qualifying these biomarkers, and 2) regulatory acceptance of their use. The clear path to address both barriers is a collaborative sharing of key qualification data amongst pharmaceutical companies with the advice of regulatory agencies. The Predictive Safety Testing Consortium (PSTC) has been organized through the C-Path Institute as a venue for sharing and critically evaluating qualification data from studies using model as well as proprietary compounds. It is the access to a wide diversity of treatments and chemical structures that the Consortium affords, and it is precisely that diversity that underpins industry and regulatory acceptance of biomarker performance. This talk will highlight the work of the PSTC and discuss models for biomarker qualification.

2:30-3:00 Markers of Disease Severity and Drug Efficacy in Alzheimer's Disease
Paul Kearney, Ph.D, Executive Director, Bioinformatics, Caprion Pharmaceuticals Inc.
Currently, there is not a blood test for Alzheimer's disease severity which makes diagnosis and assessment of drug efficacy difficult. Unfortunately, Alzheimer's affects millions of people in the US and the rate is expected to increase sharply as the population demographic ages. In this presentation a new methodology for analyzing plasma proteomic data demonstrates that there is a blood based assay that measures disease severity as accurately as the current gold standard, the Mini Mental State Examination (MMSE). Furthermore, this proteomic assay also measures the efficacy of donepezil (Aricept) treatment of Alzheimer's patients.

4:00-4:30 Lp-PLA2 - A Novel Biomarker and Target for Cardiovascular Disease Prevention
Robert Wolfert, Ph.D., Executive Vice President, R&D, diaDexus Inc.
Lipoprotein-associated phospholipase A2 (lp-PLA2) is a novel enzyme involved in the vascular inflammatory pathway leading to coronary heart disease and stroke. It has been consistently demonstrated across multiple published studies that an increase in plasma levels of the biomarker confers a doubling of risk for heart attack and ischemic stroke, and has been cleared by the FDA for both clinical indications. In addition, Lp-PLA2 appears to be involved in the causal pathway of the formation of the vulnerable, rupture-prone plaque; as such, it is a potential target for direct molecular therapeutic intervention. This paper will discuss both aspects of clinical medicine, including the intersection of the diagnostic and therapeutic applications.

4:30-5:00 PC4d is a Risk Factor for Premature and Severe Stroke
Joseph M. Ahearn, M.D., Co-Director, Lupus Center of Excellence, and Director, Research, Arthritis Institute, University of Pittsburgh School of Medicine
We have previously reported that platelets bearing complement ligand C4d are 99% specific for a diagnosis of lupus, based upon study of over 20 different diseases and healthy controls. The lupus patients positive for PC4d had a high risk of central nervous system disease. This suggested that PC4d may also identify patients at high risk of acute ischemia stroke, a disease not investigated in the original study. We have now prospectively studied PC4d in 80 patients with acute ischemic stroke. Surprisingly, PC4d was significantly associated with acute ischemic stroke and was significantly correlated with young age and with more severe stroke. These observations suggest that PC4d may be a powerful screening test for risk of stroke and prophylactic prevention.