Combination therapy for treating treat COPD

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Introduction: Chronic obstructive pulmonary disease (COPD) is a group of diseases � such as emphysema and chronic bronchitis � that affect millions of people just within the U.S. The diseases cause airflow blockage and breathing-related problems. The CDC estimates that 16 million Americans suffer from breathing problems due to this disease, and millions more suffer but have not been diagnosed and are not being treated. An enzyme known as phosphodiesterase 4B (PDE4B) plays a key role in regulating inflammation and causes exacerbation of COPD. Currently, roflumilast, a PDE4-selective inhibitor, is the main approved generic drug available for treating severe COPD patients with exacerbation. However, despite its usefulness, roflumilast also has serious side-effects, tolerance issues and less efficacy after repeated dosing, likely due to compensatory PDE4B up-regulation. Effective and improved therapies are needed that would help ameliorate the development of tolerance against roflumilast and provide continued relief to patients. Technology: Georgia State University researcher Jian-Dong Li has discovered pharmaceutical compositions that when used in combination with roflumilast may help stave-off the development of tolerance and enable continued use of the roflumilast for the treatment of COPD and other inflammatory conditions. This second composition serves to inhibit the expression or activity of the phosphodiesterase PDE4B2 either directly or indirectly. In particular, the research team has demonstrated that dexamethasone and alkenyldiarylmethane compounds are capable of reducing tolerance to roflumilast within in vitro and in vivo models of airway inflammation. This discovery presents a new promising combination strategy to improve the efficacy, decrease the effective dose, and possibly mitigate the tolerance of PDE4 inhibitors like roflumilast in patients with chronic COPD.