Background Chronic lung diseases are characterized by an increased susceptibility to infections and lung inflammation. A key function of the innate immune system is to prevent pathogen infection while limiting inflammation and oxidative stress damages.
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. HOSCN 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.
HOSCN inactivation of bacterial thioredoxin reductase may be an important mechanism by which to selectively suppress and kill persistent bacteria in the lung.
Technology New studies by Dr. Day identified selenocyanate (–SeCN) as a more potent analog of endogenous t-SCN that 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.
Potential Applications Antibacterial
State of Development Antibacterial efficacy of -SeCN has been shown in vitro against cystic fibrosis patient isolates of Pseudomonas aeruginosa, Burkholderia cepacia complex, methicillin resistant Staphylococcus aureus (MRSA) and Non Tuberculous Mycobacteria (NTM). -SeCN is also more potent than –SCN at killing these bacterial isolates including the resistant ones. –SeCN is also not toxic to human bronchial epithelial 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. -SeCN may be an effective therapeutic for the treatment of CF lung pathogens that are difficult to treat with current antibiotics.
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
Day, BJ. et al. The thiocyanate analog selenocyanate is a more potent antimicrobial pro-drug that also is selectively detoxified by the host. Free Radic Biol Med. 2020 Jan;146:324-332. PMID: 31740228
Licensing Status This technology is available for licensing.
For Further Information, Contact: Emmanuel Hilaire, PhD Director Technology Transfer Office National Jewish Health 1400 Jackson Street, Room M206b Denver, CO 80206 Voice: 303.398.1262 HilaireE@njhealth.org