METHODS FOR TREATING SCHIZOPHRENIA
Provided herein are PAK inhibitors. Also provided herein are compositions and methods for treating an individual suffering from schizophrenia.
1 .- 49 . (canceled)
50 . A method of treating one or more negative symptoms and/or cognitive impairment associated with schizophrenia comprising administering to an individual in need thereof a therapeutically effective amount of a p21-activated kinase (PAK) inhibitor.
51 . The method of claim 50 , wherein the p21-activated kinase (PAK) inhibitor modulates dendritic spine morphology or synaptic function.
52 . The method of claim 51 , wherein the p21-activated kinase (PAK) inhibitor modulates dendritic spine density and/or dendritic spine length.
53 . The method of claim 51 , wherein the p21-activated kinase (PAK) inhibitor modulates dendritic spine neck diameter.
54 . The method of claim 51 , wherein the p21-activated kinase (PAK) inhibitor modulates dendritic spine head volume and/or dendritic spine head diameter.
55 . The method of claim 51 , wherein the p21-activated kinase (PAK) inhibitor modulates the ratio of the number of mature dendritic spines to the number of immature dendritic spines.
56 . The method of claim 51 , wherein the p21-activated kinase (PAK) inhibitor modulates the ratio of the dendritic spine head diameter to dendritic spine length.
57 . The method of claim 51 , wherein the p21-activated kinase (PAK) inhibitor normalizes or partially normalizes aberrant baseline synaptic transmission associated with schizophrenia.
58 . The method of claim 51 , wherein the p21-activated kinase (PAK) inhibitor normalizes or partially normalizes aberrant synaptic plasticity.
59 . The method of claim 50 , wherein the p21-activated kinase (PAK) inhibitor normalizes or partially normalizes aberrant long term depression (LTD) associated with schizophrenia.
60 . The method of claim 50 , wherein the p21-activated kinase (PAK) inhibitor normalizes or partially normalizes aberrant long term potentiation (LTP) associated with schizophrenia.
61 . The method of claim 50 , wherein the p21-activated kinase (PAK) inhibitor normalizes or partially normalizes aberrant sensorimotor gating associated with schizophrenia.
62 . The method of claim 50 , wherein the negative symptoms associated with schizophrenia are asociality, blunted affect, avolition, alogia, anhedonia or dysphoric mood.
63 . The method of claim 50 , wherein the cognitive impairment associated with schizophrenia are impairment in executive function, comprehension, inference, decision-making, planning, learning or memory.
64 . The method of claim 50 , wherein the p21-activated kinase (PAK) inhibitor causes substantially complete inhibition of one or more p21-activated kinases.
65 . The method of claim 50 , wherein the p21-activated kinase (PAK) inhibitor causes partial inhibition of one or more p21-activated kinases.
66 . The method of claim 50 , wherein the p21-activated kinase (PAK) inhibitor is a Group I PAK inhibitor.
67 . The method of claim 50 , wherein the individual is non-responsive to treatment with an antipsychotic agent.
68 . A method for delaying or preventing the onset of schizophrenia comprising administration of a p21-activated kinase (PAK) inhibitor to an individual in need thereof.
69 . The method of claim 68 , wherein the individual has or is suspected of having risk alleles pre-disposing the individual to the development of schizophrenia.