Regulatory proteins and inhibitors

Patent metadata

Field	Value
Publication number	US-9605041-B2
Application number	US-201213367049-A
Country	US
Kind code	B2
Filing date	Feb 6, 2012
Priority date	Aug 5, 2009
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

The invention provides a previously uncharacterized protein (gamma secretase activating protein or gSAP) that activates γ-secretase to produce β-amyloid protein (Aβ). Deposition of Aβ has been associated with Alzheimer's disease and other pathologies. The invention thus additionally provides, e.g., screening methods and novel research tools, inhibitors of this novel protein, and methods of diagnosis, treatment and control of Alzheimer's disease and other neurodegenerative conditions associated with deposition of Aβ.

First claim

The invention claimed is:

1. A method for inhibiting the accumulation of abnormal protein aggregates in a warm-blooded animal in need of such inhibition which comprises:
Measuring gSAP (“gamma secretase activating protein”) expression for identifying whether the animal in need thereof has elevated expression levels and/or mutations in gSAP, wherein the animal in need thereof has elevated expression levels and/or mutations in gSAP relative to normal values as identified using a control population; and
administering to said animal an effective amount of a compound to inhibit gSAP activity,
wherein the mutations are one or more haplotypes selected from the following groups of SNPs:
a) rs6976567|rs1468682|rs1819814,
b) rs1468682|rs1819814|rs4729535,
c) rs1819814|rs4729535|rs4729540, and
d) rs7781642|rs6955503|rs7776973,

and wherein the compound to inhibit gSAP activity is selected from imatinib or a labeled derivative thereof, inhibitory RNA molecules capable of inhibiting gSAP expression, vectors and cells producing said inhibitory RNA molecules, antibodies to gSAP, and vaccines for gSAP.

2. The method of claim 1 , wherein the accumulation of abnormal protein aggregates is related to an Aβ-mediated disease, wherein the Aβ-mediated disease is selected from the group consisting of: Alzheimer's disease, memory and cognitive disorders, dementia, amyloid neuropathies, brain inflammation, nerve and brain trauma, vascular amyloidosis, and cerebral hemorrhage with amyloidosis.

3. The method of claim 1 , wherein the mutations are one or more haplotypes selected from:
c) rs1819814|rs4729535|rs4729540 and
d) rs7781642|rs6955503|rs7776973.

Assignees

• Greengard Paul
• Luo Wenjie
• He Gen
• Li Peng
• Wennogle Lawrence
• Intra Cellular Therapies Inc
• Univ Rockefeller

Inventors

• Greengard Paul
• Luo Wenjie
• He Gen
• Li Peng
• Wennogle Lawrence

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A01K2207/05

  Animals modified by non-integrating nucleic acids, e.g. antisense, RNAi, morpholino, episomal vector, for non-therapeutic purpose · CPC title