Diagnostic methods for neural disorders
First Claim
1. A method for determining an effect of a compound on a neurological condition, the method comprising:
- presenting a compound selected for treating a neurological condition to a cell sample exhibiting a genotype associated with the neurological condition, the cell sample comprising a plurality of neurons, wherein at least one of the plurality of neurons expresses an optical reporter of membrane electrical potential;
optically stimulating an optogenetic actuator in the sample following presentation of the compound, wherein the optogenetic actuator is a light gated ion channel;
generating an optical signal in response to the optical stimulation of the light gated ion channel using the optical reporter;
receiving, via a microscopy system, the optical signal generated by the optical reporter;
analyzing the optical signal generated by the optical reporter with respect to a control signal obtained from a control cell sample not exhibiting a genotype associated with the neurological condition; and
identifying the compound as a candidate for treatment of the neurological condition based on the analysis of said optical signal with respect to the control signal.
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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.
50 Citations
11 Claims
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1. A method for determining an effect of a compound on a neurological condition, the method comprising:
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presenting a compound selected for treating a neurological condition to a cell sample exhibiting a genotype associated with the neurological condition, the cell sample comprising a plurality of neurons, wherein at least one of the plurality of neurons expresses an optical reporter of membrane electrical potential; optically stimulating an optogenetic actuator in the sample following presentation of the compound, wherein the optogenetic actuator is a light gated ion channel; generating an optical signal in response to the optical stimulation of the light gated ion channel using the optical reporter; receiving, via a microscopy system, the optical signal generated by the optical reporter; analyzing the optical signal generated by the optical reporter with respect to a control signal obtained from a control cell sample not exhibiting a genotype associated with the neurological condition; and identifying the compound as a candidate for treatment of the neurological condition based on the analysis of said optical signal with respect to the control signal. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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Specification