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Name

PTPN13: A Novel Target for the Treatment of Pulmonary Fibrosis

Organization name

National Jewish Health

Profile

Background

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia, primarily occurring in older adults. It is caused by injury and aberrant repair of the lower lung resulting in accumulation of fibroblasts. These cells produce abundant amounts of collagen and contribute to the formation of scar tissue. In normal wound repair, fibroblasts die and are removed at the completion of the repair process. In IPF, fibroblasts persist and accumulate in the lung, leading to progressive fibrosis, dyspnea, hypoxemia, and death within 5 years of diagnosis.

Technology

Dr. Riches and his group have previously shown that fibroblasts normally die through apoptosis following stimulation of a receptor called Fas. Furthermore they showed that these cells will not die when Fas becomes associated with an inhibitory protein, the PTPN13 molecule. They were able to demonstrate that by blocking the association between Fas and PTPN13, fibroblast cells are once again able to undergo Fas-receptor induced death. These findings suggest that the development of a compound that blocks the Fas/PTPN13 interaction could serve as a therapeutic modality to treat IPF.

Potential Applications

Therapeutic uses for treatment of idiopathic pulmonary fibrosis. Other fibrotic conditions are being explored.

State of Development

Investigators are currently screening libraries to identify molecules that will interfere in the binding of PTPN13 to Fas.

Publications

"TNF-α Sensitizes Normal and Fibrotic Human Lung Fibroblasts to Fas-induced Apoptosis.” Frankel et al 2006 Am J Resp Cell Mol Biol 34(3): 293-304.

“Increased Cell Surface Fas Expression Is Necessary and Sufficient To Sensitize Lung Fibroblasts to Fas Ligation-Induced Apoptosis: Implications for Fibroblast Accumulation in Idiopathic Pulmonary Fibrosis.” Wynes, MW et al. The Journal of Immunology, July 1, 2011 vol. 187 no. 1 527-537.

“PTPN13 is an inhibitor of Fas-induced apoptosis in idiopathic pulmonary fibrosis.” in preparation.

Patent Status

US Patent Application 20120148528. Published international patent WO/2012/064763.

Inventors

David Riches, Ph.D., Allison Bamberg, Ph.D.

Licensing Status

This technology is available for licensing.

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