Hope on heart disease after drug breakthrough

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A potential drug candidate for a deadly heart disease is ready to move toward a clinical trial.

Calcific aortic valve disease is the most common heart valve disease in the elderly, and the third leading cause of heart disease, Australia’s main cause of death.

For patients with the condition, calcium builds up in their heart valves and vessels, until they harden. This obstructs blood flow from the heart, leading to heart failure. Presently, there are no therapies for the condition. Often the calcification gets so bad that patients have no option but to undergo dangerous heart valve replacement surgery.

“The disease is often diagnosed at an early stage and calcification of the heart valves worsens over the patient’s lifetime as they age,” says Deepak Srivastava, MD, who led the study.

“If we could intervene early in life with an effective drug, we could potentially prevent the disease from occurring. By simply slowing the progression and shifting the age of people who require interventions by five or 10 years, we could avoid tens of thousands of surgical valve replacements every year.”

Dr Srivastava is director of the Gladstone Institutes, an American not-for-profit foundation dedicated to cardiovascular research, which has been seeking the breakthrough for 15 years.

The potential therapy could also help millions of people with a congenital anomaly called bicuspid aortic valve, in which the aortic valve has only two leaflets instead of the normal three.

“We can detect this valve anomaly through an ultrasound,” explains Dr Srivastava.

“About a third of patients with bicuspid aortic valve, which is a very large number, will develop enough calcification to require an intervention.”

Dr Srivastava’s lengthy research discovered that, sometimes, valve cells get “confused and start thinking they’re bone cells, so they start laying down calcium”.

The scientists searched for “drug-like molecules” that can correct the network affected by heart valve disease, which leads to calcification.

“To do so, they first had to determine the network of genes that are turned on or off in diseased cells,” Science Daily reported.

Applying technological advancements, including gene editing, targeted RNA sequencing, network analysis, and machine learning they identified molecules that could “correct diseased cells back to the normal state”.

“In young mice who had not yet developed the disease, the therapy prevented the calcification of the valve. And in mice that already had the disease, the therapy actually halted the disease and, in some cases, led to reversal of the disease. This finding is especially important since most patients aren’t diagnosed until calcification has already begun.”

Co-lead author Christina V. Theodoris, MD, PhD says their approach offers hope for finding drugs effective for other diseases.

“Many therapeutics found in the lab don’t translate well to humans or focus only on a specific symptom. We hope our approach can offer a new direction that could increase the likelihood of candidate therapies being effective in patients.”

Dr Srivastava said it took time and technology to get results.

“By using all the knowledge we gathered over a decade and a half, combined with the latest tools, we were able to find a drug candidate that can be taken to clinical trials.

“Our ultimate goal is always to help patients, so the whole team is very pleased that we found a therapy that could truly improve lives.”

Heart disease is Australia’s leading cause of death, accounting for 11.6 per cent of all deaths.

Heart Foundation advice

One-fifth of Australians aged 45 to 74 have a high chance of having a heart attack or stroke in the next five years. Anyone 45 years and over, or 30 years and over for Aboriginal and Torres Strait Islander peoples, should have a regular Heart Health Check with their doctor. Heart Health Checks are covered by Medicare and are free at practices that bulk bill this service.

  • Smoking: Smoking damages the blood vessels to your heart, brain, and other parts of your body. This makes you three times more likely to die of a heart attack; two times more likely to die of stroke, and three times more likely to die from sudden cardiac arrest. Quitting smoking is the single best thing you can do for the health of your heart and the people around you.
  • Diet: A heart-healthy diet is one of the best ways of reducing your risk of heart disease. A heart-healthy diet is low in unhealthy fats, salt and added sugar, and rich in wholegrains, fibre, vitamins, antioxidants, and healthy fats.
  • Inactivity: Regular physical activity or exercise often can cut your risk of having a heart attack or developing heart disease. Keeping active also helps control heart disease risk factors, including high blood pressure, high cholesterol and being overweight.
  • Weight: Achieving a healthy weight can help lower your blood pressure and cholesterol and lower your risk of developing heart disease. The best way to lose weight is by slowly changing your eating habits and being more active. Start with small changes to your diet, aim for realistic goals and build up from there.
  • Alcohol: Heavy drinking or binge drinking can increase your chances of developing heart disease. Drinking a lot over the long term can increase your heart rate, blood pressure, weaken your heart muscle and increase the level of some fats in your blood (triglycerides). You can try lowering the amount of alcohol you drink by alternating with low kilojoule drinks such as plain mineral water, light beer, or low alcohol options.

Is heart disease a concern for you? Do you have at least an annual medical check?

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Written by Will Brodie


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