Methods for identifying compounds that modulate disorders related to nitric oxide/ cGMP-dependent protein kinase signaling
OwnerRalph J. Greenspan, Paul J. Shawinventors
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Abstract
The invention provides a method of identifying a compound that modulates a disease associated with a nitric oxide/cGMP-dependent protein kinase network in a mammal. The method consists of (a) administering a test compound to an invertebrate; and (b) measuring a foraging behavior of the invertebrate, wherein a compound that modulates the foraging behavior of the invertebrate is characterized as a compound that modulates a disease associated with a nitric oxide/cGMP-dependent protein kinase network in a mammal.
Claims97
A method of identifying a compound that modulates ADHD in a mammal, comprising:
- (a) administering a test compound to an invertebrate;
- and
- (b) measuring a foraging behavior of said invertebrate, wherein a compound that modulates the foraging behavior of said invertebrate is characterized as a compound that modulates ADHD in a mammal.
A method of identifying a compound that modulates hypertension in a mammal, comprising:
- (a) administering a test compound to an invertebrate;
- and
- (b) measuring a foraging behavior of said invertebrate, wherein a compound that modulates the foraging behavior of said invertebrate is characterized as a compound that modulates hypertension in a mammal.
A method of identifying a compound that modulates ADHD in a mammal, comprising:
- (a) administering a test compound to an invertebrate;
- (b) measuring an expression level for one or more polynucleotides in said invertebrate;
- and
- (c) comparing said expression level for one or more polynucleotides in said invertebrate to an expression level of one or more polynucleotides in a reference invertebrate, a compound having the effect of modulating said expression level of one or more polynucleotides associated with invertebrate foraging behavior in said test invertebrate relative to said reference invertebrate is identified as a compound that modulates ADHD in a mammal.
A method of identifying a compound that modulates hypertension in a mammal, comprising:
- (a) administering a test compound to an invertebrate;
- (b) measuring an expression level of one or more polynucleotides in said invertebrate;
- and
- (c) comparing said expression level of one or more polynucleotides in said invertebrate to an expression level of one or more polynucleotides in a reference invertebrate, a compound having the effect of modulating said expression level of one or more polynucleotides associated with invertebrate foraging behavior in said test invertebrate relative to said reference invertebrate is identified as a compound that modulates hypertension in a mammal.
A method of identifying a polynucleotide that correlates with ADHD in a mammal, comprising:
- (a) obtaining a first and a second strain of an invertebrate;
- (b) subjecting said first and second invertebrate strains to conditions in which said first strain exhibits a foraging behavior different than a foraging behavior exhibited by said second strain;
- (c) measuring an expression level for one or more polynucleotides in said first and second strains, and
- (d) identifying one or more polynucleotides that are differentially expressed in said first strain relative to said second strain, wherein a mammalian polynucleotide comprising substantially the same nucleic acid sequence as said one or more differentially expressed polynucleotides correlates with ADHD in a mammal.
A method of identifying a polynucleotide that correlates with hypertension comprising:
- (a) obtaining a first and a second strain of an invertebrate;
- (b) subjecting said first and second invertebrate strains to conditions in which said first strain exhibits a foraging behavior different than a foraging behavior exhibited by said second strain;
- (c) measuring an expression level for one or more polynucleotide in said first and second strains, and
- (d) identifying one or more polynucleotides that are differentially expressed in said first strain relative to said second strain, wherein a mammalian polynucleotide comprising substantially the same nucleic acid sequence as said one or more differentially expressed polynucleotides correlates with hypertension.
An isolated polynucleotide having ADHD-altering activity in a mammal, or fragment thereof, comprising substantially the same nucleic acid sequence as a polynucleotide selected from the group consisting of SEQ ID NOS:
- 1-75, SEQ ID NO:
- 77, SEQ ID NO:
- 79, SEQ ID NO:
- 85, SEQ ID NO:
- 87, SEQ ID NO:
- 89, SEQ ID NO:
- 91, SEQ ID NO:
- 93, SEQ ID NO:
- 95, SEQ ID NO:
- 100, SEQ ID NO:
- 102 and SEQ ID NO:
- 104.
An isolated polynucleotide having hypertension-altering activity in a mammal, or fragment thereof, comprising substantially the same nucleic acid sequence as a polynucleotide selected from the group consisting of SEQ ID NOS:
- 1-75, SEQ ID NO:
- 77, SEQ ID NO:
- 79, SEQ ID NO:
- 85, SEQ ID NO:
- 87, SEQ ID NO:
- 89, SEQ ID NO:
- 91, SEQ ID NO:
- 93, SEQ ID NO:
- 95, SEQ ID NO:
- 100, SEQ ID NO:
- 102 and SEQ ID NO:
- 104.
An isolated polypeptide having ADHD-altering activity in a mammal, or fragment thereof, comprising substantially the same amino acid sequence as an amino acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOS:
- 1-75, SEQ ID NO:
- 77, SEQ ID NO:
- 79, SEQ ID NO:
- 85, SEQ ID NO:
- 87, SEQ ID NO:
- 89, SEQ ID NO:
- 91, SEQ ID NO:
- 93, SEQ ID NO:
- 95, SEQ ID NO:
- 100, SEQ ID NO:
- 102 and SEQ ID NO:
- 104.
An isolated polypeptide having hypertension-altering activity in a mammal, or fragment thereof, comprising substantially the same amino acid sequence as an amino acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOS:
- 1-75, SEQ ID NO:
- 77, SEQ ID NO:
- 79, SEQ ID NO:
- 85, SEQ ID NO:
- 87, SEQ ID NO:
- 89, SEQ ID NO:
- 91, SEQ ID NO:
- 93, SEQ ID NO:
- 95, SEQ ID NO:
- 100, SEQ ID NO:
- 102 and SEQ ID NO:
- 104.
An isolated polypeptide having ADHD-altering activity in a mammal, or fragment thereof, comprising a polypeptide having the characteristics selected from the group consisting of molecular weight of 50 kD and pI of 4.1, a molecular weight of 28 kD and pI of 8.7, a molecular weight of 36 kD and pI of 6.0, a molecular weight of 34 kD and pI of 6.3, a molecular weight of 25 kD and pI of 5.9, a molecular weight of 12 kD and pI of 5.7, a molecular weight of 12 kD and pI of 6.4, a molecular weight of 12 kD and pI of 6.4, and a molecular weight of 29 kD and pI of 6.5.
An isolated polypeptide having hypertension-altering activity in a mammal, or fragment thereof, comprising a polypeptide having the characteristics selected from the group consisting of molecular weight of 50 kD and pI of 4.1, a molecular weight of 28 kD and pI of 8.7, a molecular weight of 36 kD and pI of 6.0, a molecular weight of 34 kD and pI of 6.3, a molecular weight of 25 kD and pI of 5.9, a molecular weight of 12 kD and pI of 5.7, a molecular weight of 12 kD and pI of 6.4, a molecular weight of 12 kD and pI of 6.4, and a molecular weight of 29 kD and pI of 6.5.
Dependencies are inferred from the claim text.