Assays and methods of diagnosis and treatment based on use of sodium channels as targets for amyloid beta or its aggregates
OwnerKai S. Lee, Xiao-Dong Sun +3inventors
InventorsKai S. Lee, Xiao-Dong Sun, Bruce M. Taylor, Dennis E. Epps, Allen E. Buhl
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Abstract
Among other things, assays and methods of diagnosis and treatment of disease (e.g., Alzheimer's disease) based on the surprising observation of an interaction between amyloid β or its aggregates with the sodium channel are provided. In particular, methods to identify compounds that modulate this interaction are provided, as well as methods of diagnosis and treatment that are based on this interaction.
Claims44
A method for identifying compounds that modulate the interaction of amyloid β or its aggregates with a sodium channel, said method comprising:
- (a) obtaining a cell that comprises a sodium channel;
- (b) contacting said sodium channel with amyloid β or its aggregates in the presence and absence of a test compound;
- and
- (c) determining the activity of said sodium channel in the presence of said test compound as compared with in the absence, wherein a test compound that impacts activity is considered a modulator of the interaction of amyloid β or its aggregates with said sodium channel.
A method for identifying compounds that modulate the interaction of amyloid β or its aggregates with a sodium channel, said method comprising:
- (a) obtaining a first cell that produces amyloid β or its aggregates;
- (b) obtaining a second cell comprising a sodium channel;
- (c) contacting said second cell with said first cell in the presence and absence of a test compound;
- and
- (d) determining the activity of said sodium channel in the presence of said test compound as compared with in the absence, wherein a test compound that impacts activity is considered a modulator of the interaction of amyloid β or its aggregates with said sodium channel.
A method for identifying compounds that modulate the interaction of amyloid β or its aggregates with a sodium channel, said method comprising:
- (a) obtaining a composition comprising a purified sodium channel;
- (b) contacting said sodium channel with amyloid β or its aggregates in the presence and absence of a test compound;
- and
- (c) determining the activity of said sodium channel in the presence of said test compound as compared with in the absence, wherein a test compound that impacts activity is considered a modulator of the interaction of amyloid β or its aggregates with said sodium channel.
A method for diagnosing Alzheimer's disease in a mammal suspected of having Alzheimer's disease, said method comprising the step of measuring the activity of a sodium channel in a cell of said mammal, wherein reduced activity of said sodium channel is correlated with the existence of an Alzheimer's disease state.
A method of screening a mammal for susceptibility to Alzheimer's disease, comprising the steps of:
- (a) isolating a cell from said mammal, said cell comprising a sodium channel;
- and
- (b) measuring activity of said sodium channel in the absence and in the presence of amyloid β or its aggregates;
- wherein reduced activity of said sodium channel in the presence of amyloid β or its aggregates as compared to in the absence is correlated with a susceptibility to developing Alzheimer's disease.
A method for diagnosing prion disease in a mammal suspected of having prion disease, said method comprising the step of measuring the activity of a sodium channel in a cell of said mammal, wherein reduced activity of said sodium channel is correlated with the existence of a prion disease state.
A method for preventing, treating, or reversing Alzheimer's disease in a mammal, said method comprising contacting a sodium channel of said mammal with a compound that protects said sodium channel from a reduction in sodium channel activity due to amyloid β or its aggregates.
A method for preventing, treating, or reversing prion disease in a mammal, said method comprising contacting a sodium channel of said mammal with a compound that protects said sodium channel from a reduction in sodium channel activity due to amyloid β or its aggregates.
A method for preventing, treating, or reversing Alzheimer's disease in a mammal, said method comprising contacting a sodium channel of said mammal with a compound that opens said sodium channel.
A method for preventing, treating, or reversing prion disease in a mammal, said method comprising contacting a sodium channel of said mammal with a compound that opens said sodium channel.
Dependencies are inferred from the claim text.