TEMPE, Ariz., March 5, 2009 (GLOBE NEWSWIRE) -- Capstone Therapeutics (Nasdaq:CAPS) today announced publication of results from the first data group of a pre-clinical study demonstrating that Chrysalin(r) (rusalatide acetate or TP508), administered following the onset of ischemia, showed a statistically significant cardioprotective benefit in a model of acute myocardial infarction (AMI or heart attack).
Using a pathophysiologically relevant model of AMI in the presence of both normal and elevated cholesterol levels, intravenous administration of Chrysalin produced a profound reduction in infarct size. Importantly, the drug was administered after ischemic insult, which reflects the anticipated clinical circumstance of a heart attack.
The study results from the normal cholesterol group are published in The Annals of Thoracic Surgery advance online publication (DOI: 10.1016/j.athoracsur.2008.12.021). The abstract is available via the following link: http://ats.ctsnetjournals.org/cgi/content/abstract/87/3/786. The investigators have submitted for publication the results from the elevated-cholesterol group.
"We are pleased to announce publication of data from the normal-cholesterol group of this landmark study," said Randolph C. Steer, MD, Ph.D., President of OrthoLogic. "There are an estimated 1.4 million heart attacks per year in the U.S. alone. Our goal is to develop Chrysalin as a therapy to limit damage to the human heart in the clinical setting of acute myocardial infarction. The study demonstrates the potential value of Chrysalin in this devastating disease state, and these data confirm the pleiotropic nature of the compound."
About the Study
The study, performed in the laboratory of Frank W. Sellke, MD, Chief, Cardiothoracic Surgical Research, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center / Harvard Medical School, demonstrated that Chrysalin extensively decreases myocardial injury when administered following a major ischemic insult. Endpoints of the study included infarct size, coronary microvessel function, myocardial function and apoptotic markers.
Methods - First Group: Normal Cholesterol
Fourteen male Yucatan pigs underwent 60 minutes of mid-left anterior descending coronary artery occlusion followed by 120 minutes of reperfusion. Pigs received either saline vehicle (control, n = 7) or TP508 (n = 7) as a bolus (0.5 mg/kg) 50 minutes into the ischemic period, followed by continuous intravenous infusion (1.25 mg/kg/h) during reperfusion. Myocardial function was monitored throughout the experiments. Monastryl blue/triphenyl tetrazolium chloride staining was utilized to measure the area at risk (AAR) and infarcted tissue. Apoptosis (programmed cell death) was assessed by Western blotting and dUTP nick-end labeling (TUNEL) staining. Coronary microvascular reactivity to endothelium-dependent factors (adenosine diphosphate, substance P, A23187) and endothelium-independent factor (sodium nitroprusside) was examined.
Results:
Global and regional left ventricular function was not significantly different between groups. Endothelium-dependent coronary microvascular relaxation was greater in the TP508 group and associated with higher endothelial nitric oxide synthase phosphorylation. Infarct size as a percentage of AAR was 23 +/- 6% in the TP508 group compared to 42 +/- 5% in the control group (p less than 0.05), a 45 percentage-point reduction. TUNEL staining was significantly decreased in the TP508 group compared with the control group (p less than 0.05). Expression of the cell survival proteins Bcl-2 (2.2-fold, p less than 0.05) and HSP-73 (1.6-fold, p less than 0.05) was higher in the TP508 group. Expression of the cell-death-signaling proteins PARP (1.6-fold, p less than 0.05), cleaved PARP (6.4-fold, p less than 0.05), and BNIP3 (3.8-fold, p less than 0.05) was significantly higher in the TP508 group in the ischemic territory.
Conclusions:
This study demonstrates that TP508 decreases infarct size, improves endothelial microvascular function, and reduces apoptosis in the setting of ischemia-reperfusion injury. Thus, TP508 may be a useful agent to attenuate myocardial reperfusion injury.
About Capstone Therapeutics
Capstone Therapeutics (trade name of OrthoLogic Corp.) 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 Chrysalin(r) (rusalatide acetate or TP508).
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. Based on its demonstrated effects in pre-clinical models and safety in clinical trials, AZX100 is currently being evaluated for commercially significant medical applications such as the prevention or reduction of hypertrophic and keloid scarring, treatment of pulmonary disease and intimal hyperplasia. Capstone has an exclusive worldwide license to AZX100.
Chrysalin, the Company's novel synthetic 23-amino acid peptide, has been proven in multiple pre-clinical and clinical models to stimulate cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues. It is currently being evaluated in disorders that involve vascular endothelial dysfunction, such as acute myocardial infarction and chronic myocardial ischemia. The Company owns exclusive worldwide rights to Chrysalin.
Capstone's corporate headquarters are in Tempe, Arizona. For more information, please visit the Company's website: www.capstonethx.com.
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Statements in this press release or otherwise attributable to CapstoneTherapeutics 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, which include the timing and acceptability of FDA filings and the efficacy and marketability of potential products, involve risks and uncertainties that could cause actual results to differ materially from predicted results. These risks include: delays in obtaining or inability to obtain FDA, institutional review board or other regulatory approvals of pre-clinical or clinical testing; unfavorable outcomes in our pre-clinical and clinical testing; the development by others of competing technologies and therapeutics that may have greater efficacy or lower cost; delays in obtaining or inability to obtain FDA or other necessary regulatory approval of our products; our inability to successfully and cost effectively develop or outsource manufacturing and marketing of any products we are able to bring to market; changes in FDA or other regulations that affect our ability to obtain regulatory approval of our products, increase our manufacturing costs or limit our ability to market our product; affects on our stock price and liquidity if we are unable to meet the requirements for continued listing on the NASDAQ Global Market; our need for additional capital in the future to fund the continued development of our product candidates; and other factors discussed in our Form 10-K for the fiscal year ended December 31, 2007, and other documents we file with the Securities and Exchange Commission.
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