The Cleveland Clinic Foundation

Other

Immunex Corporation

Xiaoxia Li

Caini Liu

Tomasz Herjan

David J Cosman

Timothy A Bird

Koichi Fukuda

Jun Qin

Lingzi Hong

Liang Zhu

Junpeng Deng

Kevin Sun

Donna Marie Driscoll

Thomas A Hamilton

Jarod Zepp

Xing Chen

George R Stark

Provided herein non-human transgenic animals comprising a genome that: i) under-expresses, or is inducible to under-express, Hu Antigen R (HuR) in at least some neurons of said transgenic animal; ii) does not express HuR, or is inducible to not express HuR, in at least some neurons of said transgenic animal; or iii) does not express functional HuR, or is inducible to not express functional HuR in at least some neurons of said transgenic animal, as well as methods of screening drugs and therapies (e.g., useful in treating ALS) using such animals.

Transgenic mice with inducible neuron-specific inactivation of HuR gene and method of screening

Provided herein are compositions, systems, kits, and methods for treating IL-17a related diseases and conditions using an SBE nucleic acid sequence that binds a SEFIR domain of an ACT1 protein.

SBE aptamers for treating IL-17a related diseases and conditions

The present invention describes compounds according to formula I: and compounds according to formula II: and additional related flavonoid compounds, as well as the use of the compounds in methods for the prevention or treatment of IL-17A-mediated disease in a subject.

Flavonoid IL-17A inhibitors

A method of treating an IL-17 mediated disease in a subject by administering to the subject a therapeutically effective amount of a of a cell-permeable decoy peptide that competitively inhibits binding of the SEFIR domain of IL-17R to the SEFIR domain of Act1. In particular, it has been determined that the &#x3b1;C helix region of the SEFIR domain of both IL-17R and Act1 plays an important role in the association of IL-17R and Act1. To facilitate cell permeation, the decoy peptide is preferably conjugated to a protein transduction domain. Examples of IL-17 mediated diseases include various human and animal inflammatory and autoimmune diseases such as asthma.

Treatment of IL-17 mediated disease by blocking SEFIR-SEFIR interactions

There are disclosed novel polypeptides referred to as Pellino polypeptides, as well as fragments thereof, including immunogenic peptides. DNAs encoding such polypeptides as well as methods of using such DNAs and polypeptides are also disclosed.

Inhibitory Pellino nucleic acids

Mutant cell lines which have lost their ability to respond to IL-1 are provided. In one embodiment, the mutant cell line lacks or is essentially free of IL-1 receptor associate kinase (IRAK), an IL-1 signaling pathway component. The present invention also provides a method for making mutant cell lines that are unresponsive to IL-1, TNF, or to both cytokines. The method comprises the steps of: transfecting cells with a Herpes Simplex Virus thymidine kinase (HSV-TK) gene and a second gene for positive selection, each of said genes being operatively linked to an IL-1 inducible promoter or a TNF inducible promoter; selecting for transfected cells that express HSV thymidine kinase and the product of the positive selection gene in response to IL-1 or TNF; determining a gancyclovir concentration which kills the selected cells in the presence of IL-1 or TNF and which does not kill the selected cells in the absence of IL-1 or TNF; mutagenizing the selected cells using a chemical mutagenizing agent; and treating the mutagenized cells with the determined concentration of gancyclovir and IL-1 or TNF. The present invention also relates to a method of identifying domains or amino acids in IRAK that are essential for IRAK to function in the IL-1 signaling pathway.

Mutant cell lines unresponsive to interleukin 1

Growing community of inventors

Cleveland, OH, United States of America

Xiaoxia Li