TEMPE, Ariz. and BOSTON, Nov. 19, 2013 (GLOBE NEWSWIRE) -- Capstone Therapeutics' (OTCQB:CAPS) joint venture, LipimetiX Development, LLC, today announced the presentation of pre-clinical data demonstrating the sustained benefit effect of their apolipoprotein E mimetic peptide (AEM-28) on established atherosclerotic lesions in Apo E null mice at the American Heart Association Scientific Sessions meeting, November 16 – 20, 2013, in Dallas, TX.
A number of technologies designed to enhance reverse cholesterol transport have been shown to prevent atherosclerotic lesion formation and/or to regress established lesions during the period of treatment. There have not been, however, any reports of these technologies having an effect on lesions after the period of treatment had ended. The purpose of this study was to determine whether the beneficial effects of an Apo E mimetic peptide on atherosclerotic lesions would be sustained after the period of treatment had ended.
"We are pleased that the American Heart Association selected for formal presentation these significant findings in this challenging murine model showing AEM-28's sustained effect on atherosclerotic lesions after the period of treatment ended. Regression of lesions is very important in the treatment of atherosclerotic vascular disease," said Dennis Goldberg, PhD, President of LipimetiX Development, LLC. "We wish to acknowledge our research partnership with Dr. G. M. Anantharamaiah and his colleagues at the University of Alabama at Birmingham for their ongoing contributions to our Apo E mimetic program. Apo E proteins have long been recognized for their role in clearing remnant lipoproteins and we are now building the case for AEM-28's direct effects on the artery wall that promote prevention as well as regression of atherosclerosis and improved vascular function."
The poster can be viewed at: www.LipimetiX.com
About The Study
Methods: Female Apo E null mice (14 weeks old, n=26) were fed Western diet for 6 weeks to establish lesions. They were then changed to normal chow for two weeks. The animals were then randomized into two groups. One group of animals (13 in each group) were administered AEM-28 (100µg/100µl of saline), retro-orbitally three times a week for four weeks, while the control group received an equal volume of saline. All animals were then continued on a chow diet for an additional four weeks without any treatment. The animals were then terminated and organs harvested. Plasma cholesterol was measured at the termination of the peptide treatment and four weeks later at organ harvest, when the animals were 30 weeks old.
Results: The Western diet raised cholesterol levels in the mice to 1373±129 mg/dl. Two weeks of chow diet resulted in a decrease of plasma cholesterol levels back to nearly the original values (475±67 mg/dl). At the end of the treatment period, AEM-28 had reduced plasma cholesterol levels significantly compared to control (375±57 mg/dl vs. 536±77 mg/dl, p < 0.001), while four weeks post peptide treatment cholesterol levels in both groups were similar (479±70 mg/dl). En face lesion analysis showed that AEM-28 treated animals had 41% less lesions compared to control (9.4±2.4% vs. 15.8+3.6%; p < 0.001). AEM-28 treated animals also had a 32% decrease in aortic sinus lesions vs. control at termination (p < 0.02). A scatter plot of the en face and aortic sinus lesion areas and end of treatment cholesterol levels show that the different treatment groups form separate clusters but there is no correlation between the extent of atherosclerotic lesions in either the en face or aortic sinus lesion areas and the plasma cholesterol levels at the end of treatment. The peptide did not cause a significant decrease in aortic sinus macrophage content. At the end of treatment, plasma from the AEM-28 group showed enhanced PON-1 activity. The increase in PON-1 activity was also maintained at study termination, four weeks later.
Discussion: Plasma cholesterol in untreated Apo E null mice rises rapidly following the end of peptide treatment. Although not measured in the first days after the end of treatment, previous work has shown that there is no difference in cholesterol between groups within a few days of the end of treatment. By the time of termination, four weeks after the end treatment, the cholesterol levels in the two groups were the same indicating that cholesterol exposure during this four week period was similar. Nonetheless, the aortas from the AEM-28 treated group demonstrated decreased lesion areas in both the en face and aortic sinus analyses, and maintained elevated PON-1, as compared to the control and group. AEM-28 and mR18L, a single domain Apo E mimetic peptide, have previously been shown to induce the same level of cholesterol reduction in the LDL-receptor null mouse, yet AEM-28 demonstrated a significantly greater lesion prevention effect.
About Capstone Therapeutics
Capstone Therapeutics is a biotechnology company committed to developing a pipeline of novel therapeutic peptides aimed at helping patients with under-served medical conditions. The Company is focused on development and commercialization of two product platforms: AZX100 and Apo E Mimetic Peptide Molecule AEM-28 and its analogs (through the LipimetiX Development, LLC, joint venture).
AZX100 is a novel synthetic 24-amino acid peptide, one of a new class of compounds in the field of smooth muscle relaxation and fibrosis. AZX100 has been evaluated for commercially significant medical applications such as the prevention or reduction of hypertrophic and keloid scarring and treatment of pulmonary and peridural fibrosis.
Apolipoprotein E (Apo E) is a 299 amino acid protein that plays an important role in lipoprotein metabolism. AEM-28 is a 28 amino acid mimetic of Apo E that contains a domain that anchors into a lipoprotein surface while also providing the Apo E binding domain that is removed by heparin sulfate receptors in the liver. AEM-28 as an Apo E mimetic has the potential to restore the ability of atherogenic lipoproteins to be cleared from the plasma, completing the reverse cholesterol transport pathway, and thereby reducing cardiovascular risk.
Capstone's corporate headquarters are in Tempe, Arizona. For more information, please visit the Company's website: www.capstonethx.com.
Statements in this press release or otherwise attributable to Capstone regarding our business that are not historical facts are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from predicted results. These risks include the factors discussed in our Form 10-K for the fiscal year ended December 31, 2012, and other documents we file with the U.S. Securities and Exchange Commission
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