GSNO Therapeutics, Inc

Development of GSNO Therapeutic’s GSNOR Inhibitors

Disease Applications

As demonstrated in the Science section, GSNORi regulates at least 56 pathophysiological drivers of many of the most important diseases of today with the most unmet medical needs. These diseases often have a complex set of drivers that makes single target/single effect drugs of limited efficacy against them. The unique advantage of GSNO Therapeutics’s GSNOR target is the multitude and directionality of responses with a single small molecule. Such positive, multi-mechanism, therapeutic effects due to inhibiting one enzyme with small molecules are rare in pharmacology. Many important diseases are based on inappropriate inflammation, oxidant/nitrosative damage, mitochondrial dysfunction, calcium dysregulation, endoplasmic reticulum stress, vascular dysfunction/hypoperfusion, hyperglycemia, misfolded proteins, MMP-9, BBB breakdown, and platelet aggregation. GSNORi inhibits all of those pathological conditions for potent therapeutic benefits.
Blue Pills Scattered on a Flat Surface
In addition, GSNORi activates IL-4, IL-10, sGC/cGMP, Nrf-2 antioxidant system for ROS & RNS inhibition, and mitochondrial prohibitin for preventing/reversing mitochondrial dysfunction and the neurotrophic factors BDNF, CNTF, Synaptophysin, and TrkB/pTrkB. GSNORi also improves and reverses deficits in memory and learning, neurological functions, and fibrosis, which suggests that GSNOR inhibition should have wide application in many important disease areas, both orphan and major: i.e., ophthalmic, neurodegenerative, cardiovascular, autoimmune, inflammatory, hepatic, renal, respiratory, and fibrotic diseases. Obviously, few of these diseases can be pursued in clinical trials by a small company, such as GSNO Therapeutics.

GSNO Therapeutics’ initial strategy is to pursue diseases that have relatively quick and less expensive clinical trials. Trials for autoimmune conjunctivitis and dry eye fit that bill, as do trials in the age-related diseases of periodontal disease, hearing loss, and hospitalized sarcopenia. The aging, diabetic vervet monkey trials currently underway should further help us refine the best approach.

GSNO Therapeutics also has encouraging preclinical data in the ovalbumin and house dust mite models of asthma, some of which were published in Ferrini et al., 2013 (please see the list of publications). GSNO Therapeutics is interested in out-licensing this application of its technology.

Other researchers have shown that GSNOR inhibition is efficacious in animal models of stroke, neurodegenerative diseases such as MS, cognitive dysfunction, spinal cord injury, inflammatory bowel disease, endothelial vasodilatory function, hypertensive kidney damage, and chronic obstructive pulmonary disease (COPD).

In addition, GSNO Therapeutics has ongoing efficacy studies on rheumatoid arthritis, type II diabetes, glaucoma, cardiovascular disease, and aging.