Human nasal olfactory epithelium as a dynamic marker for CNS therapy development
Rita Sattler1, Yoko Ayukawa, Luke Coddington
1Department of Neurology, Johns Hopkins University, Baltimore, MD 21205, USA.
Experimental Neurology
|September 28, 2011
Summary
A novel biomarker approach using nasal biopsies allows measurement of drug effects in the central nervous system (CNS). This method successfully tracked astrocyte-targeted therapies, potentially accelerating the discovery of new CNS drugs.
Area of Science:
- Neuroscience
- Pharmacology
- Biomarker Development
Background:
- Drug discovery for central nervous system (CNS) disorders faces challenges due to limited access to human brain tissue for biomarker analysis.
- Non-neuronal cells, particularly astrocytes, are increasingly recognized as key players in neurodegenerative, CNS trauma, and psychiatric diseases, making them therapeutic targets.
Purpose of the Study:
- To develop and validate a novel method for measuring pharmacodynamic changes of CNS therapeutics using accessible nasal olfactory neural tissue.
- To assess the utility of this biomarker approach for evaluating astrocyte-targeted therapies.
Main Methods:
- Development of a biopsy technique for nasal olfactory neural tissue.
- Validation of the method using thiamphenicol, an astrocyte-targeted therapeutic, in pre-clinical rodent models and a Phase 1 human clinical trial.
- Analysis of olfactory epithelial tissue to detect drug activity at the target site.
Main Results:
- The nasal biopsy method successfully measured pharmacodynamic changes induced by thiamphenicol.
- Biological activity of thiamphenicol at its target, excitatory amino acid transporter 2 (EAAT2), was confirmed in olfactory tissue from both rodent studies and human trials.
- The biomarker approach demonstrated the CNS activity of the glial-directed therapeutic.
Conclusions:
- Nasal olfactory neural tissue biopsy provides a viable and accessible method for evaluating CNS drug action, particularly for glial-directed therapies.
- This biomarker strategy can potentially overcome limitations in CNS tissue accessibility, improving the efficiency of nervous system drug discovery.
- The findings support the use of this approach for assessing the biological activity of novel CNS therapeutics targeting astrocytes.
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