METHODS FOR TREATING NEUROPSYCHIATRIC CONDITIONS
Provided herein are compositions and methods for treating a subject suffering from Fragile X syndrome, autism, Down's syndrome, mental retardation, or a neuropsychiatric condition (e.g., schizophrenia). The methods include systemic administration of a a therapeutically effective amount of a PAK inhibitor in combination with a Group I mGluR antagonist (e.g., an mGluR5 antagonist). The PAK inhibitor and mGluR antagonist can be administered together, e.g., in one pharmacological composition, or they can be administered separately.
1 - 2 . (canceled)
3 . A method for reversing some or all defects in dendritic spine morphology, dendritic spine size, dendritic spine density and/or spine plasticity in a subject with a neuropsychiatric condition comprising administering to the subject at least once an effective amount of at least one of the compounds selected from the group consisting of: a Group I PAK transcription inhibitor, a Group I PAK translation inhibitor, a Group I PAK clearance agent, an agent that binds a Group I PAK to prevent its interaction with one or more cellular proteins, a Group I PAK autoinhibitory domain polypeptide or a fragment thereof and a Group I PAK antagonist.
4 . The method of claim 1 , wherein the neuropsychiatric condition is Huntington's disease.
5 . The method of claim 1 , wherein the compound is a Group I PAK transcription inhibitor.
6 . The method of claim 1 , wherein the compound is a Group I PAK translation inhibitor.
7 . The method of claim 1 , wherein the compound is an antisense nucleic acid molecule.
8 . The method of claim 1 , wherein the compound is an RNAi.
9 . The method of claim 1 , wherein the compound is a silencing RNA.
10 . The method of claim 1 , wherein the compound is a Group I PAK clearance agent.
11 . The method of claim 1 , wherein the compound is an agent that binds Group I PAK to prevent its interaction with one or more cellular proteins.
12 . The method of claim 1 , wherein the compound is a Group I PAK antagonist.
13 - 27 . (canceled)
28 . The method of claim 1 , wherein the compound is a Group I PAK autoinhibitory domain polypeptide or a fragment thereof.
29 . The method of claim 1 , wherein the neuropsychiatric condition is schizophrenia.
30 . The method of claim 1 , wherein the neuropsychiatric condition is age-related cognitive decline.
31 . The method of claim 1 , wherein the neuropsychiatric condition is clinical depression.
32 . The method of claim 1 , wherein the defect in dendritic spine size is a reduction in dendritic spine surface area.
33 . The method of claim 1 , wherein the defect in dendritic spine size is a reduction in dendritic spine volume.
34 . The method of claim 1 , wherein the defect in dendritic spine density is a reduction of dendritic spine density.