Background Glucocorticoids (GCs) are the most potent anti-inflammatory drugs used for treatment of asthma and other chronic inflammatory or autoimmune diseases. Up to 20% of asthmatics are refractory to GC therapy and are referred to as steroid resistant (SR). SR asthmatics are characterized by increased airway inflammation that cannot be inhibited by GS treatment. Given the variable responses to corticosteroid therapy in asthmatics, alternative therapeutics are needed for personalized treatment of asthma.
Endotoxin or lipopolysaccharide (LPS) exposure, a component of the outer membrane of Gram-negative bacteria, has recently been identified as an important factor that alters cellular response to CS. It has also been implicated in asthma exacerbation.
Intracellular signaling mediated by LPS/TLR4 involves binding of a series of adaptor molecules, and leads to sequential kinase phosphorylation, such as the mitogen and stress activated protein kinase 1 (MSK1) and the transforming growth factor beta associated kinase-1 (TAK-1).
Technology Dr. Leung’s and Dr. Goleva’s laboratory identified novel biomarkers associated with asthma resistance to GC. Their lab was able to show in patient samples that elevated levels of phosphorylated MSK1 and/or phosphorylated TAK-1 correlates with resistance to corticosteroid treatment.
They also showed in an in-vitro model that treatment with a TAK-1 inhibitor was able to reverse the steroid resistance.
Potential Applications Diagnostics: detection levels of phosphorylated TAK-1 and/or phosphorylated MSK-1 in patient blood samples as an indication of corticosteroid resistance.
Treatment: use of TAK-1 and/or MSK-1 inhibitors to reverse steroid resistance in patients with an inflammatory disease.
State of Development Additional patient samples are being tested to further validate the correlation of these two biomarkers with steroid resistance.
Publications Goleva et al. Am J Resp Cr Care Med. 2013 Nov 15;188 (10):1193-201. - PMID: 24024497
Licensing Status This technology is available for licensing.
For Further Information, Contact: Emmanuel Hilaire, PhD Director Technology Transfer Office National Jewish Health 1400 Jackson St., Room M206b Denver, CO 80206 Voice: 303.398.1262 Fax: 303.270.2352 HilaireE@njhealth.org