Treating Aortic Valve Disease
Friday January 3, 2020
Aortic valve stenosis (a severe form of aortic valve disease) is the narrowing of the exit to the left ventricle of the heart. It is the most common form of valve disease, affecting more than one million patients in North America each year. Eventually, this extra work limits the amount of blood it can pump and can possibly weaken your heart muscle. Symptoms include angina, syncope and congestive heart failure.
Limiting the factors that can cause aortic stenosis with lifestyle changes may help to slow disease progression but cannot stop or reverse damage to the valve. There are no medical treatments currently available to address aortic valve disease. Surgical intervention is often required for severe cases. Once symptoms occur, they continue to worsen, and survival outcomes are poor without surgery. Treating aortic valve stenosis involves close monitoring of disease progression until surgery is indicated.
Surgical aortic valve replacement (SAVR) can relieve the symptoms of aortic valve stenosis and increase life expectancy. However, surgical interventions like SAVR and transcatheter aortic valve replacement (TAVR), a less invasive option, have serious risks including bleeding, blood vessel complications, stroke, arrhythmias, kidney disease, heart attack, infection, and even death. In some cases, patients have experienced problems with the replacement valve, such as the valve slipping out of place or leaking. Because of these risks, doctors must carefully weigh the potential risks against the potential benefits of the surgical procedure before deciding whether it is appropriate for their patients.
Approximately 14 percent of aortic valve stenosis cases are due to elevated lipoprotein(a) [also called Lp(a)], however, there are no medical treatment options currently available. Lp(a) is an inflammatory lipoprotein consisting of an oxLDL-like particle containing one molecule of apolipoproteinB-100 (apoB) that is covalently bound to a molecule of apolipoprotein(a) [called apo(a)]. Elevated Lp(a) is associated with accelerated progression of aortic valve stenosis and an increased risk of cardiovascular events such as heart attack. Elevated Lp(a) is the strongest monogenetic risk factor for coronary heart disease and stroke. Approximately 63 million people in the U.S. have inherited high Lp(a), but few realize they have high Lp(a) until a major event such as a heart attack or stroke occurs. Although a simple blood test can measure Lp(a) levels and find people who are at risk, the test is not included in standard lipid panels ordered by cardiologists and primary care doctors.
According to a recent study, traditional cholesterol tests miss 8 percent of people who have a cardiovascular event associated with aortic valve stenosis and whose only risk factor is high Lp(a). Abcentra aims to bring new medical treatment options to patients with aortic valve stenosis with elevated Lp(a).
Abcentra is developing monoclonal antibodies to treat aortic valve stenosis in patients with elevated lipoprotein(a) by inhibiting inflammatory signaling from oxidized lipids and preventing the assembly of lipoprotein(a). By targeting these mechanisms specifically, Abcentra aims to make a surgical disease into a medically treatable disease for patients at risk. Abcentra’s lead candidate, orticumab, targets a specific epitope within oxidized apoB-100 and is in development to treat aortic valve disease in patients at risk due to Lp(a). Orticumab localizes to oxLDL-rich, inflamed tissue and then forms an immune complex through binding densely aggregated oxLDL. Finally, inhibitory signaling mediated via the Fc gamma receptor II crosslinking deactivate inflammatory macrophage responses to oxidized lipids.