OUR APPROACH - Clinical Network Biomarkers

A critical component for effective clinical drug development is the availability of a biomarker for monitoring disease state and drug effects. Ideally, clinical biomarkers should correspond with key preclinical measures; typically, such biomarkers are difficult to develop in CNS diseases. However, emerging research is demonstrating that brain network activities, as measured by electroencephalogram (EEG), are robustly altered in human patient and rodent disease models. By utilizing this conservation of network activity, we are developing translational biomarkers of CNS diseases to connect our functional preclinical assays of drug effects on synaptic transmission to the clinic.

In collaboration with researchers at Harvard Medical School, we are identifying disease-specific EEG signatures to serve as clinical biomarkers for guiding compound development. Currently, we are performing EEG recordings in patients to translate our preclinical network measures identified in rodents into human disease readouts, with preliminary results demonstrating a human correlate of a mouse schizophrenia network activity signature. Further studies are supported by a cross-institutional NIH grant to identify and validate brain network activities in both humans and mice that are associated with related behavioral tasks and are similarly affected by disease state.

EEG

Through a collaborative effort between Galenea and Harvard Medical School/VA we have begun to develop translational biomarkers based on spectral measures of oscillatory brain activity. Shown above is spectral analysis of scalp EEG recorded from 68 electrodes during a novelty oddball task. We have identified novelty signatures in healthy human subjects and disease patents during this task that correlate with novelty signatures we have recorded in our in vivo mouse schizophrenia model. Precise mapping of disease phenotypes across species is essential to improve our ability to translate preclinical assessment of candidate therapeutic compounds into the identification of viable cognitive therapeutics for schizophrenia and other neurocognitive indications in the clinic.