NJH ID: #17-09
There is significant morbidity and mortality from pulmonary infections in many chronic lung diseases. Chronic lung infection result in chronic lung inflammation and the use of anti-inflammatory medication can suppress an already inadequate lung immune response. A key function of the innate immune system is to prevent pathogen infection while limiting damage due to inflammation and oxidative stress.
The innate immune system utilizes thiocyanate (–SCN) that can directly react with hypochlorite generating hypothiocyanite (HOSCN), a broad-spectrum biocide that has been extensively researched for its capabilities as an alternative antibiotic that it is harmless to human body cells while being cytotoxic to bacteria. The complete absence of thiocyanate or reduced thiocyanate in the human body, for example in cystic fibrosis, is detrimental to the human host defense system.
In previous studies the inventor identified that the lung’s innate immune response can generate HOSCN, which selectively inactivates bacterial thioredoxin reductase. Thioredoxin reductase is a critical enzyme that supplies an essential cofactor for ribonucleotide reductase which converts RNA to DNA.
Hypothiocyanite inactivation of bacterial thioredoxin reductase may be an important mechanism by which to selectively suppress and kill bacteria in the lung.
New studies by Dr. Day identified selenocyanate (–SeCN) as a more potent analog of endogenous t-SCNthat mimics the body’s immune system defenses. His studies show that –SeCN can directly react with neutrophil generated hypohalous acid such as hypochlorite to form hyposelenocyanite which is selectively detoxified by the host, but not the pathogen.
State of Development
Efficacy of -SeCN has been shown in vitro against Pseudomonas aeruginosa, Burkholderia cepacia complex, methicillin resistant Staphylococcus aureus and Non Tuberculous Mycobacteria (NTM), and is more potent than -SCN. –SeCN is also not toxic to mammalian cells at the concentrations that are lethal to these bacteria. The investigators are currently testing the in-vivo efficacy of –SeCN against various bacteria including NTM.
- Day, BJ. The science of licking your wounds: Function of oxidants in the innate immune system. Biochem Pharmacol. 2019 Mar 13;163:451-457. PMID: 30876918
Published WO/2019/046433, Other Patents Pending
Brian J. Day, Ph.D. and Preston Bratcher, Ph.D.
This technology is available for licensing.
For Further Information, Contact:
Emmanuel Hilaire, PhD
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206