NEW YORK (Reuters Health) - In patients with at-risk genetic variants in the leukotriene pathway, treatment with an experimental drug, designated DG-031, can suppress biomarkers associated with MI risk, the results of a phase II trial suggest.
Variants in the gene for the 5-lipoxygenase-activating protein (FLAP) have been linked to a heightened risk of MI. Therefore, treatment with a FLAP inhibitor could have a beneficial effect in subjects with these variants.
DG-031 is a FLAP inhibitor that has been shown to be safe and well tolerated in asthma clinical trials. Dr. Hakon Hakonarson, from Decode Genetics, Inc. in Reykjavik, Iceland, and colleagues tested DG-031’s effects on MI biomarkers in 191 patients with at-risk variants in the FLAP gene or in a leukotriene hydrolase gene.
The researchers’ findings appear in the May 11th issue of the Journal of the American Medical Association.
Compared with placebo, treatment with DG-031 was associated with significant reductions in levels of leukotriene B4 and C-reactive protein. The latter effect first became apparent after 4 weeks of treatment and a 2-week washout period and persisted for 4 more weeks.
As in previous trials, DG-031 was well tolerated and not linked to any serious side effects, the investigators point out.
The authors are hopeful that this drop in biomarker levels will translate into a reduction in MI risk. “To put these results in a historical context, we believe the promise of the beneficial role of DG-031 in cardiovascular disease may, at least in part, reflect that of statins in the late 1980s when it had been shown that they could lower LDL cholesterol but it had not been shown that lowering LDL cholesterol leads to a decrease in the risk of MI.”
In a related editorial, Dr. Christopher J. O’Donnell, from Harvard Medical School in Boston, comments that the trial “provides an exciting attempt to translate genetic findings to clinical applications.” However, he adds, “how close clinicians and researchers are to the promised destination of genome-based diagnostics and therapeutics for MI and stroke remains uncertain.”
Source: JAMA 2005;293:2245-2256,2277-2279. [ Google search on this article ]
MeSH Headings:Clinical Trials: Environment and Public Health: Epidemiologic Methods: Evaluation Studies: Health: Health Occupations: Health Services Administration: Medicine: Investigative Techniques: Population Characteristics: Preventive Medicine: Public Health: Quality of Health Care: Specialties, Medical: Epidemiologic Study Characteristics: Clinical Trials, Phase II: Health Care Quality, Access, and Evaluation: Health Care Evaluation Mechanisms: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Biological Sciences: Health CareCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
