METHOD OF TREATING ALZHEIMER'S DISEASE USING PHARMACOLOGICAL CHAPERONES TO INCREASE PRESENILIN FUNCTION AND GAMMA-SECRETASE ACTIVITY
The present invention relates to a method for treating an individual having Alzheimer's Disease by using pharmacological chaperones that bind presenelin and thereby increase γ-secretase activity.
1 . A method for treating Alzheimer's Disease in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone, wherein the pharmacological chaperone binds presenilin and thereby increases one or more of presenilin function and γ-secretase activity.
2 . (canceled)
3 . The method of claim 1 , wherein presenilin is presenilin-1.
4 . The method of claim 1 , wherein presenilin is presenilin-2.
5 . The method of claim 1 , wherein the pharmacological chaperone hinds the precursor form of presenilin with high affinity and the mature form of presenilin with low affinity.
6 . The method of claim 1 , wherein the individual has a mutation in the PSEN1 and/or PSEN2 gene.
7 . The method of claim 1 , wherein the individual is deficient in presenilin.
8 . The method of claim 1 , wherein the pharmacological chaperone increases mutant or wild type presenilin.
9 . The method of claim 1 , wherein Alzheimer's Disease is early onset familial Alzheimer's Disease.
10 . The method of claim 1 , wherein the increase in γ-secretase activity leads to an increase in the trafficking of amyloid precursor protein to the plasma membrane.
11 . The method of claim 1 , wherein the pharmacological chaperone is a compound selected from Table 2.
12 . The method of claim 1 , herein the pharmacological chaperone is G-XX.
13 . A method for the treatment of a condition resulting from the pathological aggregation of tau protein in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone, wherein the pharmacological chaperone binds presenilin and thereby increases one or more of presenilin function and γ-secretase activity.
14 . (canceled)
15 . The method of claim 13 , wherein said condition is selected from the group consisting of Fronto temporal Dementia, Alzheimer's Disease, Progressive Supranuclear Palsy, Corticobasal Degenerations and Frontotemporal Lobar Degeneration.
16 . A method for the treatment of depression in an individual, comprising administering to the individual an effective amount of a pharmacological chaperone, wherein the pharmacological chaperone binds presenilin and thereby increases one or more of presenilin function and γ-secretase activity.
17 . (canceled)
18 . The method of claim 11 , wherein the pharmacological chaperone is compound A.