A New Biologic to Treat Hypertension and Heart Disease

Inventors

Qingyu Wu, MD, PhD
Shenghan Chen

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Tony Giordano, PhD

What is it? What does it do?

The inventors found that proprotein convertase subtilisin/kexin 6 (PCSK6) is the primary activator of corin, a serine protease that processes atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), cardiac hormones that regulate salt-water balance.  pro-BNP (the unprocessed precursor of BNP) is a well-accepted biomarker of heart disease.  Knockdown of PCSK6 blocked corin activation in cardiomyocytes, led to accumulation of pro-ANP/BNP while recombinant PCSK6 rescued corin activity.  In animal models, corin knock down led to hypertension and hypertrophy, demonstrating the importance of this enzyme in maintaining cardiac heart function.  A patent application protects the use of recombinant PCSK6 as a therapeutic agent to treat cardio-renal disease.

Why is it better?

  • PCSK6 is a member of the PCSK family of proteins, for which two therapeutic inhibitors have been approved (Repatha and Praluent) targeting another family member, PCSK9 for lipid lowering.
  • ~10% of African-Americans have corin variant and increased susceptibility to heart failure, making them an ideal target population for early heart failure studies.
  • Corin variants also found in patients with renal disease.
  • The natural and sustained ability to reduce blood pressure may make PCSK6 the preferred therapy for treating heart failure and hypertension in pre-eclamptic patients.

What is its current status?

Animal studies have been completed demonstrating the importance of PCSK6 and corin in heart disease and hypertension through knock out experiments while cell systems have demonstrated that transfection of a plasmid expressing PCSK6 can increase corin activation.  More recent data has shown that corin activation by PCSK6 occurs extracellularly.  Animal studies using recombinant PCSK6 are awaiting funding.


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