US 2008/0168569 A1 · Non-invasive methods and related compositions for identifying compounds that modify in vivo aggregations of disease-related polypeptides

Abstract

Embodiments of the present invention are directed to various high-throughput methods for identifying compounds that are useful for the treatment of various neurodegenerative diseases, including the Huntington's Disease (HD), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Methods and compositions of the present invention enable the exogenous expression of one or more neurodegenerative-disease-related polypeptide variants within the ocular lens of an animal host. The formation of aggregates containing neurodegenerative-disease-related polypeptide variants increases the opacity of the lens, in a manner similar to the development of age-onset cataracts. The effect of a test compound in decreasing aggregate formation and/or destabilizing aggregates that contain neurodegenerative-disease-related polypeptide variants can be visually monitored and quantified in living animal hosts by employing conventional cataract-detecting instrumentation and related methods.

Claims33

Dependent claims

A method for screening compounds to identify active compounds, the method comprising:

determining an amount of aggregates within an ocular lens of a first animal host that has been genetically engineered to express one or more neurodegenerative-disease-related polypeptides encoded by a gene of interest, within an ocular lens of the host animal, and that has not been exposed to a test compound;
determining an amount of aggregates within an ocular lens of a second animal host that is genetically identical to the first animal host, and that has been exposed to the test compound;
comparing the determined amount of aggregates within the lens of the second animal host relative to the determined amount of aggregates within the lens of the first animal host;
and
characterizing the test compound as active when the determined amount of aggregates observed in the lens of the second animal host is less than the determined amount of aggregates observed in the lens of the first animal host.

2 more elements

Dependencies are inferred from the claim text.

Non-invasive methods and related compositions for identifying compounds that modify in vivo aggregations of disease-related polypeptides

Life of this patent

Non-invasive methods and related compositions for identifying compounds that modify in vivo aggregations of disease-related polypeptides

Life of this patent

Abstract

Claims33