Where will the next cardiovascular breakthrough come from?
pharmafile | August 17, 2017 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | British Heart Foundation, cardiovascular disease, heart, heart disease, pharma, pharmaceutical
British Heart Foundation’s Jennifer Mitchell, Research Communications Officer, explains the work they are doing to find the next breakthrough treatment for cardiovascular disease.
Over the past 50 years the number of people in the UK dying of cardiovascular disease each year has halved. This reduction in deaths can largely be attributed to an increase in society’s understanding of heart disease and the improvements in lifestyle and treatments that this knowledge has led to.
Statins are perhaps the most prolific example. Entering clinical use in the 1980s, they tackle the most common type of cardiovascular illness, coronary heart disease. They are the most commonly prescribed medicine in the UK, saving lives by reducing a person’s risk of heart conditions and stroke by stopping fatty deposits from building up inside their arteries.
However, even after the advent of statins, around 150,000 people in the UK still die each year from cardiovascular issues. How will we tackle rarer forms of cardiovascular disease, just as deadly, but as yet with no proven treatment? Where will the next breakthrough come from?
Learning from ticks
Occasionally, a viral or bacterial infection can lead to severe and potentially fatal inflammation of the heart muscle, known as autoimmune myocarditis. Around 20% of people who suffer from this go develop heart failure, which in severe cases can result in the person needing a transplant.
Myocarditis has, so far, proven difficult to diagnose and treat. This is because although the dangerous inflammation of the heart muscle seen in the disease is known to be caused by a certain type of white blood cells, called T-cells, researchers do not yet know exactly how this process occurs.
Researchers funded by the British Heart Foundation (BHF) think that we may be able to learn to design drugs targeted at this problem from an unlikely source, parasitic ticks.
During autoimmune myocarditis, chemicals called chemokines are released in the heart and attract cells that cause inflammation. If you’ve ever been bitten by a tick you will know that, unlike a mosquito bite, you do not feel it. Ticks need to feed for a long time, so they inject proteins that block your body’s chemokines and prevent painful inflammation.
Researchers at the University of Oxford have identified 31 of these tick proteins, called evasins, and are now studying which chemokines they block, and are planning to trial them in autoimmune myocarditis in mouse models. The aim is to take inspiration from the tick’s anti-inflammatory strategy and design a life-saving medicine for this dangerous heart condition.
Old drugs, new tricks
Another treatment area that also needs more research to develop new treatments is stroke medical care. Every ten seconds someone somewhere in the world has a haemorrhagic stroke – when a blood vessel bursts and bleeds into the brain. Within a year more than half of these people will have died. The only options at a doctor’s disposal to treat patients who’ve suffered a haemorrhagic stroke are blood pressure medication and – as a last resort – surgery.
Glyceryl trinitrate (GTN) is an existing drug which could provide part of the solution to the challenge of reducing the number of deaths due to haemorrhagic stroke. This drug helps lower blood pressure and opens up blood vessels, and is already used in a spray to treat angina. Now, researchers believe that it might help to reduce the damage caused in the immediate minutes and hours following a stroke.
BHF-funded researchers at the University of Nottingham are testing an adhesive patch that releases GTN, and can be applied to a stroke patient’s shoulder or back.
The patch can be applied by paramedics in an ambulance before the patient arrives at A&E, saving vital time. Providing doctors and paramedics with the means to start treating patients within an hour could revolutionise stroke care and lead to the technique being adopted worldwide.
Early trials have shown promise and now the research team are working with seven ambulance services around the UK to trial the patch on patients and chart their recovery over the 12 months following the stroke.
Testing drugs on lab-grown blood vessels
Although not strictly a cardiovascular disease, Marfan syndrome causes cardiovascular complications. Most notably, thoracic aortic aneurysm (TAA) – when the main artery leading away from the heart balloons causing a life-threatening rupture – is a leading cause of death in Marfan patients.
Currently the only treatment that prevents aortic rupture for Marfan patients suffering from a TAA is open-heart surgery to replace the damaged section of the aorta.
An estimated 13,000 people in the UK have Marfan syndrome, which is caused by mutations in a gene known as fibrillin-1. Researchers funded by the BHF took skin biopsies from two people with Marfan syndrome. They used cells from these biopsies to create stem cells known as human induced pluripotent stem cells (hiPSCs). They then used these stem cells to create smooth muscle cells – cells which make up the wall of our blood vessels.
Using the blood vessel model, the researchers have already found that the pathway initially thought to be responsible for the development of TAAs in people with the syndrome only makes up part of the picture. These findings may explain why clinical trials for drugs acting to disrupt this have proven disappointing so far.
By using the blood vessel models the researchers were able to tell that a separate pathway was, in fact, more critical in causing the aneurysms. The team now hope to use the lab-generated vessel cells to test drugs which target this new avenue for their potential to prevent people with Marfan syndrome from developing a TAA.
Gene-editing
If left undetected and untreated, an inherited heart condition can sadly lead to heart failure or even sudden death from cardiac arrest. For many families, the first sign there’s a problem is when someone dies suddenly with no obvious cause or explanation.
Hypertrophic cardiomyopathy (HCM) is a genetic condition caused by a change or mutation in one or more genes and is passed on through families. If you have HCM, the muscular wall of your heart – the myocardium – becomes thickened, making the heart muscle stiff. This thickening makes it harder for your heart to pump blood out of your heart and around your body and can also lead to life-threatening arrhythmias.
Decades of BHF research has discovered many of the genes responsible for HCM so that genetic testing can be carried out for families at risk. However, there is no cure.
Gene-editing is a relatively new and hugely exciting field which could see the cure for inherited heart disease by simply swapping a faulty, disease-causing gene for a ‘healthy’ gene. Of course, this type of genetic manipulation has unique ethical considerations and has not been tested in humans, but there are already examples of success in animal models.
There are many diseases which fall under the cardiovascular disease ‘umbrella’ for which treatments are at best limited and at worst non-existent. A standout example is heart failure, where the only treatment for many is a heart transplant.
Our great strides in cardiovascular research have resulted in a dramatically reduced death-rate from heart attack. Now we must strive to find treatments for those heart attack patients left with heart failure, for people with severe myocarditis, for those who’ve suffered a devastating stroke, and for others, with rarer forms of heart disease.
Related Content
LGC Group opens $100M Organic Chemistry Synthesis Centre of Excellence
LGC Group, a life sciences company, has opened its new Organic Chemistry Synthesis Centre of …
Novo Nordisk unveils new semaglutide data on obesity and heart disease at ECO 2025
Danish biopharma, Novo Nordisk, has announced that it will present new data on metabolic and …
Johnson & Johnson announces successful results from trial for myeloma treatment
Global healthcare company, Johnson & Johnson, announced that analysis of its Darzalex (daratumumab) therapy showed …
