Method to predict and prevent oxygen-induced inflammatory tissue injury
Inventors
Sitkovsky, Michail V. • Thiel, Manfred
Assignees
National Institutes of Health NIH • Juno Therapeutics Inc • US Department of Health and Human Services
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8455437-B2
Publication Date
2013-06-04
Expiration Date
2026-01-25
Abstract
Methods for modulating responsiveness to increased oxygen levels in an at-risk subject identifying an at-risk subject; and before exposing the identified at-risk subject to an increased amount of oxygen, administering to the at-risk subject an anti-inflammatory agent wherein the responsiveness of the at-risk subject to said increased amount of oxygen is modulated as compared to the responsiveness of the at-risk subject to said increased amount of oxygen in the absence of said anti-inflammatory.
Core Innovation
The invention provides methods for modulating the responsiveness of an at-risk subject to increased oxygen levels by administering an anti-inflammatory agent prior to exposure to the increased oxygen. This approach aims to prevent or reduce oxygen-induced inflammatory tissue injury by compensating for oxygen's disruption of physiological anti-inflammatory mechanisms mediated through hypoxia-induced adenosine and its receptor A2AR.
This invention addresses the problem that oxygen therapy, particularly in patients with ongoing inflammation, can exacerbate pulmonary inflammation and tissue damage. Oxygen abolishes hypoxia that normally induces extracellular adenosine accumulation and subsequent activation of immunosuppressive A2 adenosine receptors on activated immune cells, thereby disrupting a critical tissue-protecting anti-inflammatory pathway. Consequently, oxygen treatment itself may lead to iatrogenic lung injury and worsen outcomes in diseases like acute lung injury and ARDS.
The method involves identifying subjects at risk, such as those with active inflammatory diseases, and prior to oxygen administration, delivering at least one anti-inflammatory compound. These compounds include A2A adenosine receptor agonists and agents that modulate adenosine levels or receptor expression. By maintaining or enhancing anti-inflammatory signaling during oxygen therapy, the invention prevents or minimizes oxygen-induced exacerbation of inflammation and tissue damage, thereby improving the safety and efficacy of oxygen therapy.
Claims Coverage
The patent contains two independent claims focusing on methods to reduce tissue damage associated with oxygen therapy by administration of an anti-inflammatory agent before oxygen exposure.
Anti-inflammatory agent administration prior to oxygen therapy
Administering a therapeutically effective amount of an anti-inflammatory agent consisting of an A2A adenosine receptor agonist to an at-risk subject before oxygen therapy to reduce or inhibit tissue damage compared to no administration prior to oxygen exposure.
Method for reducing inflammatory lung injury associated with oxygen therapy
Administering a therapeutically effective amount of an anti-inflammatory agent consisting of an A2A adenosine receptor agonist to an at-risk subject prior to oxygen therapy, wherein the inflammatory lung injury is reduced or inhibited compared to absence of prior anti-inflammatory administration.
The claims cover methods of pre-treating at-risk subjects with A2A adenosine receptor agonists to prevent or reduce tissue damage and inflammatory lung injury caused by subsequent oxygen therapy administered by various means.
Stated Advantages
Prevention or minimization of oxygen therapy-associated exacerbation of inflammation and tissue damage.
Rescue of subjects from oxygen therapy-induced death and lung injury.
Provision of a method to safely administer oxygen therapy in patients with ongoing inflammation.
Improved outcomes in diseases like acute lung injury and ARDS by maintaining physiological anti-inflammatory pathways during oxygen administration.
Documented Applications
Use in oxygen therapy for patients with inflamed lungs and bronchi, including ARDS, COPD, and asthma.
Treatment and prevention of pulmonary and systemic inflammatory diseases and trauma-associated inflammatory complications.
Prevention of ischemia-reperfusion induced inflammatory tissue injury.
Use in oxygen therapies administered by inhalation, hyperbaric chambers, oxygen-saturated blood transfusions, or recreational oxygen exposure.
Treatment of inflammatory responses in conditions such as organ transplantation, autoimmune diseases, circulatory pathologies, angioplasty, stent placement, and grafting.
Interested in licensing this patent?