The ability of inhaled pyruvate to regulate Nitric Oxide (NO) levels in lungs can be used to reduce lung inflammation, or can be used to treat lung infections.
In four separate human clinical trials it was demonstrated that inhaled sodium pyruvate regulated the synthesis of NO and also protected it from destruction by excess hydrogen Peroxide. Sodium pyruvate is an antioxidant that reacts directly with oxygen radicals like hydrogen peroxide and peroxynitrite, neutralizing them and thusly protecting DNA and other cellular components, such as glutathione, lipids and proteins.
The ability to control the levels of NO is important. Over production or under production is detrimental and produces various diseases in both the lungs and nasal cavities. Pyruvate, at 5mM levels, protects NO and increases its production, thus can be used in diseases where NO production is low, i.e. in smokers, mild asthmatics, in intubated or tracheostomized patients, in normal subjects after exercise and hyperventilation, COPD patients, cancer patients, in patients with cystic fibrosis, lung infections, and in diseases with excess inflammation. NO is also markedly reduced in the nasal cavities of children suffering from cystic fibrosis, in patients with chronic sinusitis, allergic rhinitis, with respiratory disorders and pre-eclampsia. Patients who produce excess NO include those with Kartagener’s syndrome, moderate or severe asthma, sarcoidosis, and fibrosing alveolitis. NO is also elevated in the nasal cavities of healthy newborns and in healthy adults. Increased NO levels are chemotactic for eosinophils, which produce and enhance inflammation, especially if it is transformed into peroxynitrite. Eosinophils affect dyspnoea perception in asthma by releasing neurotoxins. Inhaled B2 agonists do not have any effect on NO production and this presumably affects their lack of effect on chronic inflammation in asthma. Acute treatment with corticosteriods during an exacerbation of asthma is associated with a decline in NO values in adults and children. The inhalation of low levels of sodium pyruvate was also shown to reduce NO levels in asthmatic and COPD patients.
The FDA has determined that N115 has sufficient safety toxicology and clinical data to proceed with the multi-dose, extended use, clinical trials. Phase III/Phase IV studies will focus on Pulmonary Fibrosis, Unmet Needs and COPD patients. On the basis of existing clinical data, EmphyCorp is confident that its Investigative New Drug, N115, can and will be used for maintenance or continuous treatment of patients over extended periods of time. The Company believes that N115 will set the standard in the pharmaceutical industry for the treatment of major pulmonary diseases.