Algorae Pharmaceuticals (ASX: 1AI) has obtained positive results from preclinical studies, which evaluated the cardioprotective qualities of its drug candidate AI-168.
Algorae has undertaken preclinical assessments at the Monash University Victorian Heart Institute Research Laboratories to further assess the formulation of AI-168 and compare the performance of AI- 168 with beta blockers using well-established in vitro models of cardiovascular disease.
Three cardiovascular cell lines were used to assess the dysregulation of cell growth caused by cardiac stressors.
In the first model, human umbilical vein endothelial cells (HUVECs) were treated with Angiotensin II (AngII). Angiotensin II is known to play a significant role in the pathophysiology of cardiovascular diseases.
When HUVECs are grown the presence of AngII, there is a significant reduction in cell proliferation.
While the addition of beta blocker alone did resolve some loss of cell proliferation, the AI-168 combination was able to effectively restore normal cell proliferation, with a relative improvement of approximately 94% from vehicle to control (healthy cells with no stressors or pharmaceutical intervention).
In the second model, human pulmonary artery smooth muscle cells (hPASMCs) were treated with platelet derived growth factor (PDGF). The aberrant activation of the PDGF signalling pathway has been demonstrated to drive progression of cardiopulmonary diseases. When hPASMCs are grown the presence of PDGF, there is a significant increase in uncontrolled cell proliferation.
In this model, the addition of the beta blocker alone had a minimal effect on PDGF-mediated cell proliferation, whereas AI-168 was able to restore cell proliferation to near normal levels, with a relative improvement (normalisation) of cell proliferation by approximately 80% from vehicle to control.
In the third model, rat cardiomyoblasts were treated with doxorubicin. Doxorubicin is an anthracycline, which is an important class of chemotherapeutic drugs used for the treatment of several types of cancer. A known adverse effect of anthracycline treatment is chemotherapy-induced cardiotoxicity, which can occur during or after the completion of treatment. In this model, doxorubicin was shown to be toxic to the cardiomyoblasts, causing cell death and/or significantly reducing cell proliferation.
By contrast, AI-168 restored approximately 68% of the cardiomyoblast growth lost to doxorubicin toxicity.
The results observed from these in vitro assays will be used to identify the most appropriate in vivo models of cardiovascular disease, which Algorae is evaluating in conjunction with the Monash University researchers.