Optimalisering: Novel therapy for treatment-resistant hypertension

Resistant hypertension (RHT) is a frequent disease and causes premature morbidity and death. RHT is defined as high blood pressure that remains above goal despite the use of three antihypertensive drugs of different classes. The prevalence of RHT continues to rise. Thus, the development of novel drugs that can control the elevated blood pressure in these patients is urgent and of high social and clinical impact for several millions of people worldwide. Natriuretic peptides play an important role in the regulation of blood pressure and it is shown that patients with RHT have an impaired natriuretic peptide system. In this project we are developing small molecular compounds to target the natriuretic peptide receptor-A (NPR-A) for the treatment of patients with resistant hypertension. We have earlier identified compounds showing activity by high-throughput screening and in-silico design. We have developed these compounds to improve the pharmacological properties. We have built a large library of compounds and we have increased our knowledge about structure-activity relationship. We have now decided for one candidate that showed low preclinical cytotoxicity and high selectivity towards our target NPR-A compared to a pharmacological screening panel of receptors, enzymes, transporters and ion-channels. We are now ready to start a proof-of-concept study in an animal model of hypertension. Our long-term goal is to offer a good treatment for patients with uncontrolled high blood pressure.

Prosjektet har gitt økt kompetanse hos prosjektdeltagerne både med tanke på å lede et prosjekt med kommersialiseringspotensiale, samarbeide med og få råd fra aktører utenfor akademia og ikke minst at vi har økt vår kunnskap om hva som kreves på veien for å få et stoff på markedet. Dette er verdifull erfaring for prosjektdeltakerne som kan brukes i fremtidige prosjekter Prosjektdeltagerne har også fått innsikt i hva som skal til for at investorer skal kunne vise interesse. Prosjektet vil på sikt kunne vise seg å ha stor samfunnsverdi ettersom et nytt legemiddel for resistent hypertensjon vil være svært verdifullt. Hypertensjon hos pasienter kan føre til prematur død, uførhet og store utgifter for helsevesenet. Dette er derfor en byrde for pasienten selv og samfunnet både lokalt og nasjonalt. Nye legemidler som kan redusere risiko for alvorlige sykdommer vil være en økonomisk investering da behovet for dyr behandling vil kunne reduseres.

Resistant hypertension (RHT) is a frequent disease and causes premature morbidity and death. RHT is defined as high blood pressure that remains above goal despite the use of three antihypertensive drugs of different classes. The prevalence of RHT continues to rise. Thus, the development of novel drugs that can control the elevated blood pressure in these patients is urgent and of high social and clinical impact for several millions of people worldwide. Natriuretic peptides play an important role in the regulation of blood pressure and it is shown that patients with RHT have an impaired natriuretic peptide system. In this project we are developing small molecular compounds to target the natriuretic peptide receptor-A (NPR-A) for the treatment of patients with resistant hypertension. We have recently performed a high-throughput screening and identified three compounds showing activity. We further want to develop these compounds to improve the pharmacological properties with the goal to go through a proof-of-concept study in an animal model of hypertension at the end of the project period. Thus, in this project we will further synthesize novel compounds and the best active compounds will go through preclinical cytotoxicity and pharmacokinetic testing to enable a proof-of-concept study. Our long-term goal is to offer a good treatment for patients with uncontrolled high blood pressure.