Identifying Pharmacodynamic Protein Markers of Centrally Active Drugs in Humans: A Pilot Study in a Novel Clinical Model
Citations Over TimeTop 15% of 2007 papers
Abstract
Recognizing specific protein changes in response to drug administration in humans has the potential for significant utility in clinical research. In spite of this, many methodological and practical questions related to assessing such changes are unanswered. We conducted a series of clinical studies to assess the feasibility of measuring changes in proteins related to drug administration using a mass-spectrometry proteomics technique capable of quantifying hundreds of proteins simultaneously in cerebrospinal fluid (CSF) and plasma. Initially, the normal variability of proteins in these compartments was characterized in 16 healthy volunteers over a 2-week period. Drug-associated changes were subsequently assessed in the plasma and CSF proteomes of 11 subjects given atomoxetine, which served as a selective, centrally active probe to test the model. Protein levels in the CSF and plasma were unchanged between visits in the normal variability study. In contrast, statistically significant changes were detected in the CSF protein pattern after drug treatment. These studies suggest that identification of changes in the CSF proteome associated with the administration of centrally active drugs is feasible, and may be of value in the development of new drugs, as well as broader clinical research.
Related Papers
- → Cancer proteome-expression database: Genome Medicine Database of Japan Proteomics(2010)13 cited
- → Proteome and Proteomics for the Research on Protein Alterations in Aging(2001)12 cited
- → Mouse models for neurodegenerative diseases and a theory of proteomics(2003)
- Research Progress on Proteomic Techniques and their Applications(2014)
- → Proteomics in Shaping the Future of Biofertiliser Delivery Technique(2023)