Reactive airway diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD) cause contractions in smooth muscle cells lining the airways, resulting in coughing, wheezing, and difficulty breathing. Current treatment options for these diseases depend on either non-specific blockade of inflammatory pathways in the lungs or activating beta-adrenergic receptors on the smooth muscle cells of the airway. These bronchodilators, however, are ineffective for some patients and can cause toxic side effects in others. This technology is a new combination therapy that targets two classes of cellular proteins, chloride channels and chloride co-transporters, resulting in relaxation of the smooth muscle cells that line the airway. While currently marketed drugs target these proteins individually for non-respiratory indications, this technology provides a new method for targeting these proteins simultaneously and specifically to relax smooth muscle cells for patients with restrictive airways diseases. As such, this technology acts as a safe alternative/adjunct treatment for asthma, COPD, and potentially other restrictive airway diseases that are caused by constriction of airway smooth muscle, such as cystic fibrosis and adult respiratory syndrome.
This technology uses a combination therapy to simultaneously block (1) calcium-activated chloride channels (CaCC) and (2) sodium-potassium-chloride cotransporters (NKCCs), thereby resulting in relaxation of constricted airway smooth muscle in patients with asthma or COPD. Under normal circumstances, activation of both of these channels induces a "chloride cycle" that results in smooth muscle cell depolarization and persistent contraction. Interruption of the "chloride cycle" relaxes the airways for symptom relief. While diuretics such as furosemide and bumetanide block NKCC cotransporters, and some non-steroidal anti-inflammatory medications can block CaCCs, there are no established agents that can block both these targets simultaneously for the purpose of smooth muscle relaxation.
Consequently, this technology can potentially grow to become a pipeline of smooth muscle relaxants that can be used for multiple indications beyond asthma and COPD. This includes relief from other restrictive airway diseases such as cystic fibrosis and adult respiratory syndrome, as well as relaxation of vascular, bladder, and uterine smooth muscle cells for the treatment of hypertension, bladder spasms, and pre-term labor, respectively. Taken together, this technology provides a platform for a myriad of potential blockbuster drugs that provide a safe method for smooth muscle relaxation.
This technology has been demonstrated to significantly reduce contractility in both human and guinea pig airway smooth muscle.
Patent Pending (WO/2012/134965)
Tech Ventures Reference: IR 2845, 2859, CU12213