Phosphodiesterase-9 inhibition versus/plus neprilysin inhibition as novel treatments for heart failure.
Heart failure (HF) remains a leading cause of death and disability in New Zealand, and new treatments are needed. The natriuretic peptides (NPs) are hormones whose actions, including favourable effects on blood pressure and the kidneys, mitigate HF symptoms and delay its progression. Augmentation of the NPs, via inhibition of the enzyme neprilysin which degrades these peptides, in conjunction with angiotensin-receptor-blockade (ARNi), further improves outcomes in HF. However, neprilysin inhibition will alter levels of multiple factors in addition to those relating to the NPs, some likely deleterious. An alternative may be inhibition of phosphodiesterase-9 (PDE9), an enzyme identified as specifically reducing NP-signalling and believed to contribute to HF worsening. It is also possible that further amplification of NP levels/bioactivity through combined neprilysin/PDE9-inhibition might have added benefits.The present application aims to assess for the first time the efficacy of inhibition of PDE9 versus neprilysin as HF therapies – comparing their effects separately as well as investigating the potential added benefits of combining PDE9 and neprilysin inhibition.These studies will produce highly original information helping define the role and therapeutic potential of PDE9 inhibition in HF and may lead to a novel treatment strategy for this disease.
Dr Scott conducted her undergraduate studies at the University of Otago, New Zealand, graduating with a BSc Honours in Biochemistry in 2003. Her Honours Project was The Effect of Cryoprotective Agents and Freezing on the Redox Status of Murine Fibroblasts. She was awarded a CMRF Summer Studentship in 2003 to determine if Npr-1 knockout and wild-type mice differed in heart weight, blood pressure, infarct size and in plasma levels of cardiac hormones following myocardial infarction.More About Dr Nicola Scott