Diagnostic methods for neural disorders
First Claim
1. A method of characterizing a neurological condition, the method comprising:
- obtaining a human-derived cell having a mutation associated with a condition;
expressing an exogenous optical reporter and an exogenous optical voltage actuator in the cell;
illuminating the optical voltage actuator expressed by the cell or a neighboring cell, wherein the optical voltage actuator initiates an action potential in response to the illumination as an optical stimulation;
detecting an optical signature generated by the optical reporter in response to the optical stimulation of the cell; and
comparing the detected signature to an expected signature detected from control cell, wherein a difference between the observed signature and the expected signature provides information about the condition.
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Abstract
The invention generally relates to optical methods for the diagnosis of neuronal condition by converting a cell from a patient into a neuron and optically evaluating action potentials of that cell in vitro. The cell is transformed with an optical reporter and exhibits an optical signature in response to neural stimulation. Using genome-editing, a control cell can be made that is isogenic but-for a known mutation and a control signature obtained from the control cell. Thus, methods of the invention reveal potential neurodegenerative effects of a mutation as manifested in a patient'"'"'s genetic context. The optical signature of the cell, or the difference between the signature and the control signature, is correlated to a diagnosis of the neurodegenerative disease.
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Citations
18 Claims
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1. A method of characterizing a neurological condition, the method comprising:
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obtaining a human-derived cell having a mutation associated with a condition; expressing an exogenous optical reporter and an exogenous optical voltage actuator in the cell; illuminating the optical voltage actuator expressed by the cell or a neighboring cell, wherein the optical voltage actuator initiates an action potential in response to the illumination as an optical stimulation; detecting an optical signature generated by the optical reporter in response to the optical stimulation of the cell; and comparing the detected signature to an expected signature detected from control cell, wherein a difference between the observed signature and the expected signature provides information about the condition. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A method of diagnosing a condition, the method comprising:
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obtaining a cell from a patient suspected of having the condition; expressing an exogenous optical reporter and an exogenous optical voltage actuator in the cell; illuminating the optical voltage actuator expressed by the cell or a neighboring cell, wherein the optical voltage actuator initiates an action potential in response to the illumination as an optical stimulation; detecting an optical signature from the optical reporter in response to the optical stimulation of the cell; and comparing the detected signature to an expected signature detected from control cell, wherein a difference between the observed signature and the expected signature corresponds to a diagnosis of the condition; and generating a report that includes the diagnosis for the patient. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18)
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Specification