Protein therapy for acute respiratory distress syndrome (ARDS

This technology utilizes delivery of a protein that strengthens pulmonary endothelial cell junctions, in order to potentially treat acute respiratory distress syndrome (ARDS) and acute lung injury (ALI).

Unmet Need: Curative therapy for ARDS and acute lung injury

Acute respiratory distress syndrome (ARDS), also known as acute lung injury (ALI) in its less severe form, is a life-threatening condition in which fluid fills the lungs, compromising their ability to provide oxygen to the blood and vital organs. Current therapies for ARDS can ameliorate symptoms by removing some of the fluid buildup and providing breathing support in the form of mechanical ventilation. However, none of these therapies are preventative, resulting in mortality rates as high as 30% with current treatments. There is need for therapies that address the underlying fluid accumulation in the lungs, in order to improve patient outcomes.

The Technology: Focal adhesion kinase to treat underlying cause of ARDS and ALI

This technology uses an activated form of focal adhesion kinase (FAKp) to strengthen cell junctions that form a barrier in pulmonary endothelia. Endothelial barriers become compromised in diseased lungs, and fluid can flow from the blood vessels into the alveoli, destroying their function in the lung. This damage can result in ALI and ARDS. By strengthening the barriers in the blood vessels of alveoli, this technology can directly treat the underlying cause of ARDS and ALI. FAKp can be delivered with ChariotTM, a commercially available protein delivery system, and can also be histidine-tagged and chelated to a metal ion such as copper, nickel, cobalt or zinc for optimized delivery.

This technology has been successfully tested in vivo using direct infusion of FAKp protein in mice.

Applications:

• Treatment of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)
• Treatment of tumor metastasis in cancer
• Treatment of inflammatory diseases such as sepsis, arthritis, hepatitis, arthritis, hyaline membrane disease, and cerebral inflammation
• Treatment of pulmonary and cerebral edema
• Treatment of neonatal bronchopulmonary dysplasia

Advantages:

• Offers direct treatment of ARDS, rather than simply treating symptoms
• Can utilize a number of commercially available transport proteins, such as Chariot, perpetratin, and thrombin-antithrombin (TAT) fragment for optimized delivery
• FAKp may be fused to a histidine tag that can be linked to metals such as copper, nickel, and zinc
• May be administered through an intravenous, buccal, parenteral, or oral route, or via inhalation

Lead Inventor:

Jahar Bhattacharya, M.D., Ph.D.

Patent Information:

Patent Status

Related Publications:

• Quadri, S., and Bhattacharya, J. “Resealing of Endothelial Junctions by Focal Adhesion Kinase” Am J Physiol Lung Cell Mol Physiol. 2007; 292: L334-42.

• Safdar, Z., Yiming, M., Grunig, G., and Bhattacharya, J. “Inhibition of Acid-induced Lung Injury by Hyperosmolar Sucrose in Rats” Am J Resp Crit Care Med. 2005; 172: 1002-1007.

• Quadri, S., Bhattacharjee, M., Parthasarathi, K., Tanita, T., and Bhattacharya, J. “Endothelial Barrier Strengthening by Activation of Focal Adhesion Kinase” J Bio Chem. 2003; 278: 13342-13349.

• Safdar, Z., Wang, P., Ichimura, H., Issekutz, A.C., Quadri, S., and Bhattacharya J. “Hyperosmolarity enhances the lung capillary barrier” J Clin Invest. 2003; 112(10): 1541-1549.

Tech Ventures Reference:

• IR 2335

• Licensing Contact: Joan Martinez