A Multi-Targeted Antisense Oligonucleotide-Based Therapy Directed at Phosphodiesterases 4 and 7 for COPD

Recent drug development for chronic obstructive pulmonary disease (COPD) has focused on strategies aimed at reducing the underlying inflammation by selective inhibition of phosphodiesterases (PDE), specifically the PDE4 isoforms. The anti-inflammatory and bronchodilator activities of PDE4 inhibitors have been well documented (Giembycz &Field 2010), however their clinical development has been hampered by their low therapeutic ratio and dose-dependent systemic side effects. PXS TPI1100 is an inhaled drug candidate consisting of two modified antisense oligonucleotides (AON) directed at PDE isoforms 4B, 4D and 7A. PXS TPI1100 has been designed to reduce the recruitment and persistence of inflammatory cells in COPD through an unique mechanism of action and has the potential to be a novel, highly effective approach for this respiratory disease.