SUMMARY:
Researchers from UCLA’s Department of Anesthesiology have developed an oral combinatory therapy that holds enormous implications in healthcare for the complete attenuation of aneurysm formation.
BACKGROUND:
Aortic aneurysms are abnormal protrusions in the major blood vessels from the heart to the rest of the body. These protrusions which develop in 4-9% of the population especially those who are males and smokers, are common: affecting millions of people nationwide. Because of the weakened integrity of the remodeled vessel walls, these aneurysms have a high potential for rupturing and causing life threatening internal bleeding to result in death in more than 95% of the cases, making early intervention crucial.No oral medicines have been available to treat or regress aortic aneurysms and the only available treatment option is surgical correction in large aneurysms with a size over 5.5 cm.Majority of patients suffer from silent growth and lethal rupture of the aneurysms, also due to lack of early diagnostic strategies that have been recently developed at UCLA as well (cite two other patents on Biomarkers for Abdominal/Thoracic Aortic Aneurysm). Therefore, novel treatment options are in urgent need to manage the devastating and prevalent disease of aortic aneurysms.
INNOVATION:
UCLA researchers in the Department of Anesthesiology have found a novel combinatory therapy for the full abrogation of aneurysm formation. Capitalizing on previous research that found a causal role of eNOS uncoupling/H4B deficiency in aneurysm formation, a research team led by Dr. Hua Cai identified the combination therapy of folic acid (FA) and Nifedipine, for its role in attenuating abdominal aortic aneurysm (AAA) formation as well as thoracic aortic aneurysm formation. The researchers fed customized food tablets containing FA in combination with Nifedipine for 4 weeks to murine models of AAA. They demonstrated that combinatory therapy with FA and either a low or high dose of Nifedipine has remarkable synergy in reducing incidence of aneurysms. Notably, the researchers demonstrated that FA and high dose Nifedipine completely attenuated aneurysm formation to zero occurrence, and also completely abrogated all of the pathophysiological and molecular changes underlying aneurysm formation. To confirm attenuation, they also showed that FA and Nifedipine together reduced superoxide production, a common symptom of AAA. Vascular remodeling and medial layer elastin degradation were completely alleviated by combinatory therapy with FA and high dose Nifedipine. Translation of this technology into oral therapeutics for clinical use could provide a non-invasive cure for aortic aneurysms that is in urgent need to revolutionize effective clinical management of the di .
POTENTIAL APPLICATIONS:
● Oral medicine to effectively remedy aortic aneurysms
● Novel therapeutic for cardiovascular and pulmonary diseases, such as diabetes and hypertension, with dysfunctional eNOS
ADVANTAGES:
● Oral administration removes risks and complications from surgery
● Completely abrogates aortic aneurysm formation
● Reverses effects of large and small aneurysms.
● Folic acid and Nifedipine are commonly prescribed medicines presently with thoroughly published safety data
DEVELOPMENT-TO-DATE: Researchers have successfully demonstrated efficacy of the folic acid and Nifedipine combinatory therapy at attenuating abdominal aortic aneurysms via oral treatment in murine models. This conclusion is supported by ultrasound definition of aortic aneurysm growth and inhibition, and pathophysiological and molecular assessments of abrogated aortic aneurysm development.