A protein therapy for Acute Respiratory Distress Syndrome (ARDS)

Acute Respiratory Distress Syndrome (ARDS), also known as Acute Lung Injury (ALI) in its less severe form, is a life-threatening lung condition in which fluid fills the lungs and prevents them from providing oxygen to the blood and vital organs. ARDS can have a number of different triggers, including physical trauma and infections such as pneumonia and sepsis. Worldwide, ARDS kills upwards of 50,000 individuals per year, putting it on par with breast cancer in terms of mortality. Current therapies for ARDS can remove some of the fluid buildup in the lungs and provide breathing support in the form of mechanical ventilation, but have no ability to halt the production of the fluid itself. As a result, even the most effective currently available ARDS treatment strategies have a mortality rate of up to 30%. This technology directly treats and reduces the production of fluid in sick and injured lungs through the action of a protein, focal adhesion kinase (FAKp), and has the potential to dramatically improve ARDS patient outcomes.

Treatment of injury, not management of symptoms

In a healthy lung, extremely fine blood vessels pass through small air sacs known as alveoli, and semi-permeable cell barriers allow oxygen to move from the air-filled alveoli into the blood. When these barriers become compromised, fluid can flow from the blood vessels into the alveoli, destroying their function in the lung. Over time, persistent flooding of these important lung structures can cause widespread collapse of alveoli and severely reduced lung function results. By strengthening the fluid barriers in the blood vessels of the alveoli, FAKp has the ability to treat the cause of ARDS directly, unlike currently available treatments. 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 delivery.

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

Lead Inventor:

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

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:

• Direct treatment of ARDS
• Can utilize a number of commercially available transport proteins, such as Chariot, perpetratin, and thrombin-antithrombin (TAT) fragment
• FAKp may be fused to a histidine tag which can be linked to a variety of metals including copper, nickel, and zinc.
• May be administered through an intravenous, buccal, parenteral, or oral route, or via inhalation.

Patent Information:

Patent Issued (US 8,420,080)

Patent Pending (WO/2009/046129)

Tech Ventures Reference: IR 2235/2710

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.