Apelin against aneurysm
New treatment for people with cardiovascular diseases
New research from the University of Alberta paves the way for the creation of a drug that helps protect people from cardiovascular diseases by increasing the body's natural protective functions, according to a press release from U of A researchers developing new treatment that could help protect people with cardiovascular disease.
Cardiologist Gavin Oudit and his research team found a link between a peptide called apelin and a reduction in abdominal aortic aneurysm, which has been shown to significantly reduce mortality in mice.
Oudit's team hopes to replicate these results in patients suffering from cardiovascular diseases or at risk of cardiovascular diseases, in particular abdominal aortic aneurysms, and has created a biotech startup to commercialize their discovery.
In a series of trials using mice with aortic aneurysms and aneurysm samples from humans, a group that also includes University of Alba scientists John Vederas and Zamaneh Kassiri found a significant improvement in health in mice treated with apelin compared to those who did not receive it: none of the mice treated died, whereas 50% of the untreated mice died.
Modern treatment of aortic aneurysm is limited to behavioral changes, such as smoking cessation or surgical treatment. There are no medical or pharmaceutical treatments that are effective at reducing the rate of aortic aneurysm development, but Oudit hopes to change this with a synthetic form of apelin that can be delivered to patients intravenously.
According to Oudit, who is also the director of the Cardiac Functions Clinic at the Albert Mazankovsky Heart Institute, in the fight against cardiovascular diseases, one can distinguish "good guys" - such as apelin, a peptide found naturally in several organs, such as the heart, liver, brain and lungs, and "bad guys" – hormones or chemicals in the body that need to be reduced or blocked so that the patient can become healthier.
"We've made great strides in blocking the 'bad guys,' especially with medications like ACE inhibitors or beta blockers to treat symptoms," Oudit said. "But our research focused on developing a method to improve the 'good guys' so that they work better and primarily protect people from cardiovascular diseases, including heart attacks and heart failure."
Although apelin showed quite promising properties as a treatment option, the team needed to develop the most stable version that would not be immediately destroyed by other enzymes in the body. The scientists identified the enzymes that attack and decompose apelin, and then developed a way to protect the apelin molecule from being destroyed too quickly by enzymes. According to Oudit, this process took the team five years, and as a result, a synthetic version of apelin was obtained, which now decomposes not in a few minutes, but in a few days.
"This is chemical engineering at its best," he said. – We have developed an analogue that is noticeably resistant to destruction, and when we use it in our animal models, we can completely protect them from [cardiovascular] diseases. We have achieved zero mortality."
At the same time, Oudit's team claims that the apelin analogue can help not only in the treatment of abdominal aortic aneurysms, but also in other diseases.
"We have seen (as a result of using an analogue) excitatory effects in the kidneys in renal failure, in the heart in heart failure, in the rest of the cardiovascular system in pulmonary arterial hypertension (vascular lung disease)," said Oudit. "What we have created is, in fact, insulin for the cardiovascular system."
Audit predicts that in just two years his team will receive a version of the apelin analogue that they can test on humans.
"Our goal is to get this drug to patients as soon as possible," Oudit said. – It's exciting because we completely led the discovery and development of these apelin analogues. I think this is a great example of how translational research can start with a molecule, then move on to an animal model so that we can get an idea of its clinical applicability and finally turn it into new treatments for our patients."
Article by Wang et al. Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs is published in PNAS – VM.
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