Procizumab- new hope to restore heart function in sepsis induced cardiac depression

Researchers have found in a new study that Procizumab promptly restored cardiac dysfunction in a preclinical sepsis model by inhibiting the cardiac depressant factor DPP3. The current findings indicate that DPP3 plays an important role in septic cardiomyopathy.

Procizumab is a humanized monoclonal antibody in preclinical development specifically binding circulating Dipeptidyl Peptidase 3 (DPP3).

Dipeptidyl Peptidase 3 (DPP3) is an active enzyme which, when released into the blood, inactivates angiotensin II, a hormone that is important for the heart function. This inactivation leads to cardiac depression and consequently hemodynamic instability and consequently cardiac depression.

The study data (1) from the team lead by Prof. Alexandre Mebazaa have shown that high DPP3 blood values are associated with decreased heart function in a preclinical sepsis model. In this randomized, controlled study, the administration of Procizumab immediately and significantly improved heart function by increasing cardiac output, stroke volume, and left ventricular shortening fraction. Inactivation of the cardiac depressant factor DPP3 fully restored cardiac contraction and improved survival.

DPP3 is at the core of a recently discovered disease mechanism, which was previously demonstrated to be a leading cause of circulatory failure (2,3,4). The release of the cardiac depressant factor DPP3 into the bloodstream causes the inactivation of the heart-stimulating hormone, Angiotensin II, a process leading to cardiac depression, hemodynamic instability and shock.

"These findings demonstrate for the first time that DPP3 plays a role in sepsis. By inhibiting DPP3 with our antibody Procizumab, we are able to restore cardiac function in preclinical sepsis models. This paves the way for future investigations on the utility of Procizumab as a possible therapeutic option in patients with sepsis and septic shock" said Dr. Andreas Bergmann, CEO of 4TEEN4.

The antibody Procizumab offers a new approach for the treatment of life-threatening diseases related to acute circulatory failure. Preclinical safety and toxicity studies of the antibody as well as the initiation of the first-in-man studies are planned for 2021.

References

(1) Deniau (2020) Inhibition of circulating dipeptidyl-peptidase 3 restores cardiac function in a sepsis-induced model in rats: A proof of concept study, PLOS ONE, doi.org/10.1371/journal.pone.0238039

(2) Deniau (2019) Circulating dipeptidyl peptidase-3 is a myocardial depressant factor: DPP3 inhibition rapidly and sustainably improves hemodynamics, European Journal of Heart Failure, DOI: 10.1002/ejhf.1601

(3) Takagi (2019) Circulating dipeptidyl-peptidase 3 and alteration in hemodynamics in cardiogenic shock: Results from the OptimaCC Trial, European Journal of Heart Failure, doi: 10.1002/ejhf.1600

(4) Dépret (2020) Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients, Critical Care, doi: 10.1186/s13054-020-02888-5