The J. David Gladstone Institutes

Qin Xu

Yadong Huang

Karl H Weisgraber

Robert W Mahley

Clare Peters-Libeu

Thu Nga Bien-Ly

Ligong Chen

Provided are methods and compositions for identifying candidate agents for treatment of obesity, liver disease, and/or diabetes. Such methods include, e.g., contacting a mammalian cell or cell population with a test agent, and measuring an expression level and/or activity level of ClpP in the mammalian cell or in cells of the cell population. Also provided are methods and compositions for treating an individual (e.g., one who is obese and/or has diabetes). Treatment methods include administering an inhibitor of ClpP to the individual (e.g., to prevent or reduce weight gain, to increase insulin sensitivity, and/or to increase glucose tolerance).

Methods and compositions for treating obesity and/or diabetes and for identifying candidate treatment agents

The present disclosure provides methods of identifying a candidate agent for treating an apoE-associated neurodegenerative disorder. The methods involve contacting a PCSK1 or a PCSK2 polypeptide with an apolipoprotein E polypeptide in the presence of a test agent.

Compositions and methods for identifying agents for treating apoE-related diseases

The present disclosure provides synthetic antibodies specific for an epitope present on an apolipoprotein E polypeptide. The antibodies are useful in various treatment, diagnostic, and monitoring applications, which are also provided.

Antibody specific for apolipoprotein and methods of use thereof

The present invention provides nucleic acids comprising a nucleotide sequence encoding an apolipoprotein E (apoE) splice variant, e.g., an unprocessed apoE, that retains intron 3; and vectors and host cells comprising same. The present invention further provides screening methods to identify agents that inhibit cleavage of intron-3 from the apoE splice variant. The present invention further provides methods of treating apoE-related neurological disorders, involving administering an agent that inhibits removal of intron-3 from a precursor apoE mRNA.

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Burlingame, CA, United States of America

Qin Xu