Cell-based assays are a promising tool for drug discovery, particularly in neuronal and cardiac diseases where molecular targets are often unknown.  The key to an effective assay is the readout: how did the test compound affect the cell?  Electrophysiology is considered the gold standard for characterizing electrically active cells (neurons and cardiomyocytes); but conventional electrophysiology is not amenable to high-throughput studies needed for drug discovery.

 

Q-State Biosciences combines optogenetics, stem cell technology, and advanced optical imaging to create in vitro models of neuropsychiatric, neurodegenerative, and cardiac diseases using genetically diverse human cells.  The company leverages the voltage-indicating protein (VIP) and advanced imaging platforms developed in the lab of Adam Cohen and the stem cell-based models of neurodegenerative diseases developed in the lab of Kevin Eggan, both at Harvard University, to provide a new approach to preclinical drug development.

 

Q-State technologies enable, for the first time, all-optical electrophysiological characterization of human disease models.  This advance comes from three core technologies:

• Optogenetic reporters and actuators.  A protein derived from a Dead Sea microorganism converts action potentials into visible flashes of fluorescence that are readily detected in a microscope (see figure).  We imaged activity in primary and hiPSC-derived neurons and cardiomyocytes.

• Stem cell-based disease models.  Recent advances in genome editing, stem cell protocols, and direct reprogramming enable creation of cell-based disease models with fully characterized genetic background and direct reference to clinical data from the human donor.

• Advanced instrumentation.  Custom microscope systems optically stimulate and record electrical propagation in cells, in culture or in intact tissue, with unprecedented speed, sensitivity, and spatial resolution. Sophisticated bioinformatics algorithms automatically convert large movie files into biologically meaningful data on cellular function and response to drugs.

 

The Q-State technology is qualitatively unique for its ability to provide patch clamp-like data, with higher throughput, lower cost, and higher information content than current manual or automated patch clamp assays, and with better temporal and spatial resolution and lower phototoxicity than other optical screening tools.

 

In the video below, listen to Q-State co-founder Adam Cohen describe the Q-State technology and how we use it to develop new diagnostics and therapies for neuropsychiatric and neurodegenerative diseases.

Watch the video