Eliezer A Masliah

US Patent:

6455757, Sep 24, 2002

Filed:

Mar 4, 1999

Appl. No.:

09/262519

Inventors:

Lennart Mucke - Foster City CA
Tony Wyss-Coray - Berkeley CA
Eliezer Masliah - Chula Vista CA

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

A01K 6700

US Classification:

800 12, 800 3, 800 18

Abstract:

The present invention features non-human transgenic animal models for Alzheimers disease (AD) and CAA, wherein the transgenic animal is characterized by 1) expression of bioactive transforming growth factor-1 (TGF-1) or 2) both expression of bioactive TGF-1 and expression of a human amyloid precursor protein (APP) gene product. The transgenic animals may be either homozygous or heterozygous for these alterations. Bigenic animals are further characterized by development of AD-associated and/or CAA-associated pathology within about two to three months of age, and at about twelve months of age are characterized by a reduced number of neuritic plaques relative to singly transgenic animals. The invention also features methods of screening for biologically active agents that facilitate reduction of -amyloid deposits in vivo and methods for facilitating reduction of formation of neuritic plaques in a subject susceptible to AD.

US Patent:

7226746, Jun 5, 2007

Filed:

Oct 6, 1999

Appl. No.:

09/806842

Inventors:

Eliezer Masliah - San Diego CA, US
Makoto Hashimoto - La Jolla CA, US
Edward Rockenstein - Chula Vista CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

G01N 33/53

US Classification:

435 71, 435 72, 435 721, 435 78, 435 79, 435 793, 436501, 436503

Abstract:

In methods for screening treatments for, and treatment of, neurodegenerative diseases, aggregation in neurons of NACP/α-synuclein is measured and expression of a non-amyloidogenic protein is stimulated in order to reduce the level aggregration. For purposes of screening agents for treatment of neurodegenerative disease, oxidative stress in the neuronal cells is stimulated by introducing a mixture of metal-ions and hydrogen peroxide. Examples of appropriate metals include iron, aluminum, and copper. After introduction of the agent under evaluation for stimulation of expression of non-amyloidogenic protein, the effectiveness is measured by testing for a decrease in the level of aggregation of NACP/α-synuclein. In an exemplary embodiment, the non-amyloidogenic protein is β-synuclein. The aggregation of NACP/α-synuclein is dependent upon the concentration of metal ions in the neuronal cells.

US Patent:

7276643, Oct 2, 2007

Filed:

Feb 20, 2001

Appl. No.:

10/204337

Inventors:

Eliezer Masliah - San Diego CA, US
Edward Rockenstein - Chula Vista CA, US
Hersey Mallory, legal representative - Encinitas CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

A01K 67/027
G01N 33/00
C12N 5/02

US Classification:

800 18, 800 3, 435325

Abstract:

The methodologies of the present invention demonstrate that a critical balance between pro- and anti-amyloidogenic molecules exists that regulates amyloid formation and cell death in Alzheimer's disease and Parkinson's disease. β-Synuclein, the non-amyloidogenic homologue of α-synuclein, is a negative modulator of α-synuclein and Aβ aggregation, having neuroprotective properties against α-synuclein and Aβ neurotoxicity and that β-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that β-synuclein blocks Aβ aggregation either by direct inhibition of Aβ amyloidogenesis or indirectly via either α-synuclein or its 35 a. a. NAC region, inferring neuroprotective characteristics within the effected cells. The generation of a transgenic mouse line and a cell system overexpressing α-synuclein characterizes the mechanisms by which β-synuclein blocks α-synuclein and Aβ aggregation and that this mechanism offers protection to the cell against amyloid formation as seen in the pathologies of Alzheimer's disease and Parkinson's disease.

US Patent:

7393994, Jul 1, 2008

Filed:

Aug 20, 2001

Appl. No.:

09/933640

Inventors:

Eliezer Masliah - San Diego CA, US
Edward Rockenstein - Chula Vista CA, US
Margaret E. Mallory - Encinitas CA, US

Assignee:

Regents of the University of California - Oakland CA

International Classification:

G01N 33/00
A01K 67/027

US Classification:

800 3, 800 18

Abstract:

Alzheimer's disease, Parkinson's disease and Lewy body disease are the most commonly found neurodegenerative disorders in the elderly. The invention is a transgenic mouse that contains two transgenes, human α-synuclein and human amyloid precursor protein, which are responsible for the formation of the neuritic plaques, Lewy bodies and neurodegeneration seen in the above mentioned diseases. The transgenic mouse is an accurate model for disease by both functional and pathological assays.

US Patent:

7459601, Dec 2, 2008

Filed:

May 24, 2004

Appl. No.:

10/853774

Inventors:

Eliezer Masliah - San Diego CA, US
Makoto Hashimoto - La Jolla CA, US
Edward Rockenstein - Chula Vista CA, US
Lennart Mucke - San Francisco CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

A01K 67/00
A01K 67/033
A01K 67/027
C12N 5/06
C12N 5/10

US Classification:

800 12, 800 18, 435354

Abstract:

In methods for screening treatments for, and treatment of, neurodegenerative diseases, aggregation in neurons of NACP/α-synuclein is measured and expression of a non-amyloidogenic protein is stimulated in order to reduce the level aggregration. For purposes of screening agents for treatment of neurodegenerative disease, oxidative stress in the neuronal cells is stimulated by introducing a mixture of metal-ions and hydrogen peroxide. Examples of appropriate metals include iron, aluminum, and copper. After introduction of the agent under evaluation for stimulation of expression of non-amyloidogenic protein, the effectiveness is measured by testing for a decrease in the level of aggregation of NACP/α-synuclein. In an exemplary embodiment, the non-amyloidogenic protein is β-synuclein. The aggregation of NACP/α-synuclein is dependent upon the concentration of metal ions in the neuronal cells.

US Patent:

7727957, Jun 1, 2010

Filed:

Oct 31, 2003

Appl. No.:

10/699517

Inventors:

Dale B. Schenk - Burlingame CA, US
Eliezer Masliah - San Diego CA, US

Assignee:

Janssen Alzheimer Immunotherapy - Little Island, County Cork
The Regents Of The University Of California - Oakland CA

International Classification:

A61K 38/17
A61K 39/395
A61K 39/00
A61K 39/385

US Classification:

514 12, 4241301, 4241851, 4241931, 4242781

Abstract:

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

US Patent:

7795495, Sep 14, 2010

Filed:

Feb 15, 2007

Appl. No.:

11/675607

Inventors:

Eliezer Masliah - San Diego CA, US
Edward Rockenstein - Chula Vista CA, US
Makoto Hashimoto - La Jolla CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

A01K 67/027
A01K 67/00
G01N 33/00

US Classification:

800 18, 800 3, 800 9

Abstract:

The methodologies of the present invention demonstrate that a critical balance between pro- and anti-amyloidogenic molecules exists that regulates amyloid formation and cell death in Alzheimer's disease and Parkinson's disease. β-Synuclein, the non-amyloidogenic homologue of α-synuclein, is a negative modulator of α-synuclein and Aβ aggregation, having neuroprotective properties against α-synuclein and Aβ neurotoxicity and that β-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that β-synuclein blocks Aβ aggregation either by direct inhibition of Aβ amyloidogenesis or indirectly via either α-synuclein or its 35 a. a. NAC region, inferring neuroprotective characteristics within the effected cells. The generation of a transgenic mouse line and a cell system overexpressing α-synuclein characterizes the mechanisms by which β-synuclein blocks α-synuclein and Aβ aggregation and that this mechanism offers protection to the cell against amyloid formation as seen in the pathologies of Alzheimer's disease and Parkinson's disease.

US Patent:

8147833, Apr 3, 2012

Filed:

Feb 22, 2008

Appl. No.:

12/528439

Inventors:

Dale B. Schenk - Burlingame CA, US
Eliezer Masliah - San Diego CA, US
Manuel J. Buttini - Emeryville CA, US
Tamie J. Chilcote - San Francisco CA, US
Edward Rockenstein - Chula Vista CA, US
Kate Dora Games - Belmont CA, US

Assignee:

Neotope Biosciences Limited - Dublin
The Regents of the University of California - Oakland CA

International Classification:

A61K 39/395

US Classification:

4241331, 4241391, 4241411

Abstract:

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.