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Method Of Treating Silicosis And Other Occupational Lung Diseases

Background:
The National Cancer Institute's Laboratory of Experimental Immunology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of treating silicosis and other occupational lung diseases

The inhalation of dust containing crystalline silica particles causes silicosis, an incurable lung disease that progresses even after dust exposure ceases. Over a million US workers are exposed to silica dust annually, and thousands worldwide die each year from silicosis. The pulmonary inflammation caused by silica inhalation is characterized by a cellular infiltrate and the accumulation of chemokines, cytokines, and Reactive Oxygen Species (ROS) in bronchoalveolar lavage fluid.

Macrophages are the predominant immune cell type present in alveolar spaces. The uptake of silica particles by macrophages triggers the production of ROS (including hydrogen peroxide) via the oxidative stress pathway, which in turn contributes to pulmonary damage and macrophage death.

Technology:
One strategy for limiting the production of pro-inflammatory cytokines and ROS after silica exposure involves treatment with "suppressive" oligonucleotides (ODN).  Suppressive ODN express motifs based on the repetitive TTAGGG hexamers present at high frequency in the telomeric ends of self DNA. 

This invention describes methods for treating, preventing, or reducing the risk of developing occupational lung diseases using ODN treatment.  Preclinical in vivo studies show that pre-treatment with suppressive ODN reduces silica-dependent pulmonary inflammation.  Preclinical in vivo studies also showed that treatment with suppressive ODN also reduced disease severity and improved the survival of mice exposed to silica.

Further R&D Needed:

• Develop a mouse model to examine whether suppressive ODN prevent silica-induced lung cancer
• Establish the utility of suppressive ODN in the prevention/treatment of acute and chronic diseases caused by various pulmonary irritants, including but not limited to asbestos and beryllium

• AODN-based therapeutics for the treatment of silicosis