|Discovery research||Preclinical trials||Clinical trials
Worldwide, Chronic Obstructive Pulmonary Disease (COPD) affects 329 million people or nearly 5% of the population. Asthma it currently affects about 300 million people1. Asthma and COPD prevalence is growing, WHO reports that COPD predicted to be third leading cause of death in 2030. Asthma is a chronic inflammatory disease of the airways characterized by bronchospasm. COPD is characterized by chronically poor airflow, it typically worsens over time. The main causes of asthma and COPD are smoking especially during pregnancy and low air quality from factors such as traffic or industrial pollution
Both asthma and COPD cannot be cured. Existing drugs can relief poor airflow or bronchospasm caused by asthma and COPD, but they cause two main problems.
The first problem is sufficient side effects that existing airways dilating drugs or bronchodilators have. One group of these drugs are β2-agonists (alupent, ventolin, salbutamol, berotec, etc.) as a side effects they lead to expressed tachycardia, headache, dizziness, muscular tremor. Another group of existing bronchodilators are M-cholinoblockers (atropine and its analogs) they also cause multiple side effects and hence aren't applied independently but typically with β2-agonists.
The second problem is a tolerance caused by long period of β2-agonists or M-cholinoblockers application. Many chronic patients have a long history of β2-agonists or M-cholinoblockers application or both, that cased a tolerance for these drugs. As a result all currently existing drugs in the world no longer help to a 30%-50% of chronic patient with asthma or COPD. This situation is mortally dangerous for this large group of patients.
GUR-501 targets to a third, not used so far, type of targets for regulation of bronchial tone. This is EP4 receptor for prostaglandin Е2 (PGE2). Relaxing effect of PGE2 on bronchial smooth muscle as strong as that of β2-agonists, but at the same time the side effects can be significantly reduced, since it is a natural endogenous bioregulator in human body. The use of natural PGE2 for the relief of bronchospasm is impossible because it causes severe coughing. This restriction is overcome in the molecule GUR-501, containing only natural components: PGE2 linked to NO-donor component via glycerin linker moiety. GUR-501 molecule makes it possible not only eliminating the impact on cough receptors, but also enhancing the activity in 20 times compared to the natural PGE2, resulting in a significant decrease in therapeutic dose and additional safety for the patients (inability of overdose, practically no side effects). In addition, there is no side effect of capillary dilation leading to edema of the bronchi, which can be observed when using β2- agonists. Second potential biological target for GUR 501 (after NO releasing) may be soluble guanylate cyclase. GUR -501 may be the only effective medicine for patients with a long history of asthma who have developed a tolerance to the existing bronchodilators.