mRNA Breakthrough Offers a Potential Heart Attack Cure

King’s College London researchers are turning to the same technology behind the mRNA COVID-19 vaccines to develop the first damage-reversing heart attack cure. They used mRNA to deliver the genetic instructions for specific proteins to damaged pig hearts, sparking the growth of new cardiac muscle cells. “The new cells would replace the dead ones and instead of forming a scar, the patient has new muscle tissue,” lead researcher Mauro Giacca said. Researchers are turning to the same technology behind Pfizer and Moderna’s vaccines to develop the first damage-reversing heart attack cure.

Diseases of the heart are the leading cause of death around the world; the WHO estimates that 17.9 million people died from cardiovascular disease in 2019, representing almost a third of all deaths. Of those, 85% are ultimately killed by heart attacks and strokes. Heart attacks occur when blood flow to parts of the heart is blocked, often due to fat or cholesterol build up. The cardiac muscle cells — marvelous little powerhouses that keep you beating throughout your entire life — are starved of oxygen and can be damaged or killed. Left in its wake is not the smoothly pumping cardiac muscle, but instead scar tissue.

We are all born with a set number of muscle cells in our heart and they are exactly the same ones we will die with. The heart has no capacity to repair itself after a heart attack,” explained Giacca.

At least, until now. To develop their heart attack cure, the researchers turned to mRNA, which delivers the instructions for protein creation to cells. Whereas the Pfizer and Moderna vaccines instruct cells to make the spike protein of SARS-CoV-2, priming the immune system against the virus, the same technology can deliver a potential heart attack cure by carrying the code for proteins that stimulate the growth of new heart cellsPharmaTimes reported. In an experiment with pigs (a close match for the human heart), the mRNA treatment stimulated new heart cells to grow after a heart attackregenerating the damaged tissues and creating new, functional muscle rather than a scar.

According to BioSpace, harnessing mRNA in this way has been dubbed “genetic tracking,” named for the way the mRNA’s progress is tracked via the new proteins it is creating. The technique is being explored to create vaccines for pathogens like HIV, Ebola, and malaria, as well as cancers and autoimmune and genetic diseases. While thus far their heart attack cure has only been successfully tested in porcine pumpers, the team hopes to begin human clinical trials within the next couple years. “Regenerating a damaged human heart has been a dream until a few years ago,” Giacca said, “but can now become a reality.”

Source: https://www.freethink.com/

New AI Algorithm Can Spot Unseen Heart Attack Symptoms

Researchers at Mount Sinai have created a new artificial intelligence algorithm that can identify slight changes within the heart and accurately predict an incoming heart attack symptoms or heart failure. The AI algorithm could learn how to identify subtle changes in electrocardiograms (also known as ECGs or EKGs) to predict whether a patient was experiencing heart failure.

Researchers implemented natural language processing programs to help the computer extract data from the written reports and enabling it to read over 700,000 electrocardiograms and echocardiogram reports obtained from 150,000 Mount Sinai Health System patients from 2003 to 2020. Data from four hospitals was used to train the computer, whereas data from a fifth one was used to test how the algorithm would perform in a different experimental setting.

“We showed that deep-learning algorithms can recognize blood pumping problems on both sides of the heart from ECG waveform data,” said Benjamin S. Glicksberg, PhD, Assistant Professor of Genetics and Genomic Sciences, a member of the Hasso Plattner Institute for Digital Health at Mount Sinai, and a senior author of the study published in the Journal of the American College of Cardiology: Cardiovascular Imaging. “Ordinarily, diagnosing these type of heart conditions requires expensive and time-consuming procedures. We hope that this algorithm will enable quicker diagnosis of heart failure.”

“However, recent breakthroughs in artificial intelligence suggest that electrocardiograms—a widely used electrical recording device—could be a fast and readily available alternative in these cases. For instance, many studies have shown how a “deep-learning” algorithm can detect weakness in the heart’s left ventricle, which pushes freshly oxygenated blood out to the rest of the body. In this study, the researchers described the development of an algorithm that not only assessed the strength of the left ventricle but also the right ventricle, which takes deoxygenated blood streaming in from the body and pumps it to the lungs.”

Although appealing, traditionally it has been challenging for physicians to use ECGs to diagnose heart failure. This is partly because there is no established diagnostic criteria for these assessments and because some changes in ECG readouts are simply too subtle for the human eye to detect,” said Dr. Nadkarni. “This study represents an exciting step forward in finding information hidden within the ECG data which can lead to better screening and treatment paradigms using a relatively simple and widely available test.”

Source: https://www.mountsinai.org/

Predicting Heart Attack and Stroke Risk 10 Years Before

A new risk calculator that can better predict people at high risk of heart and circulatory diseases years before they strike, is ready for use across the UK and Europe researchers say. The risk calculator, SCORE2, enables doctors to predict who is at risk of having a heart attack or stroke in the next 10 years with greater accuracy.

Researchers say the tool will help to save people from having a potentially deadly heart attack or stroke, ultimately saving livesPeople who are flagged as having an increased risk can be put on personalised preventative treatment, such as statins, or will receive lifestyle advice to lower their risk. 

Around 200 investigators and researchers across Europe analysed data from nearly 700,000 participants – mostly middle-aged – from 45 different studiesWhen recruited to the studies, participants had no prior history of heart and circulatory disease, and in the 10 years they were followed up, 30,000 had a cardiovascular event – including fatal or non-fatal heart attack or stroke.

The risk tool was statistically recalibrated, by using regional-specific cardiovascular and risk factor data from 10.8 million people, to more accurately estimate cardiovascular risk for populations split into four European risk regionsIt uses known risk factors for heart and circulatory diseases such as age, sex, cholesterol levels, blood pressure and smokingThe calculator accounts for current trends in heart and circulatory diseases, can predict both fatal and non-fatal conditions and is adaptable to countries with different levels of risk. Researchers say it can better estimate the cardiovascular risk amongst younger people, and will improve how treatment is tailored for older people and those in high-risk regions across Europe. 

Professor Emanuele Di Angelantonio, BHF-funded researcher at the University of Cambridge BHF Centre of Research Excellence, said: “This risk tool is much more powerful and superior than what doctors have used for decades. “It will fit seamlessly into current prevention programmes with substantial real-world impact by improving the prevention of cardiovascular diseases across Europe before they strike.”
Professor Sir Nilesh Samani, medical director at the British Heart Foundation and cardiologist, said: “This new risk tool is a major advance and will save many more people from developing heart attacks, stroke and heart disease, all of which develop silently over many years and strike without warning. “It will be the new gold standard for doctors to determine which patients are at the highest risk of these conditions, and enable tailored treatment and lifestyle advice to be given much earlier.”

One Pill A Day Reduces Heart Attack Risk By One Third

A cheap, single pill taken once a day that combines four common drugs is safe and reduces the risk of events such as heart attacks, strokes and sudden death in people over the age of 50, research has found. The study, the first large-scale trial to date, looked at the effectiveness of a so-called polypill – a four-in-one therapy containing drugs to lower cholesterol and blood pressure that was first proposed more than 15 years ago. The researchers found those taking the polypill had a more than 30% lower risk of serious heart problems than those just offered advice.

While different formulations have been studied, previous trials have only been conducted in small groups of people and over short periods of time. These studies have primarily looked at the impacts of cholesterol on blood pressure, relying on models to predict the impact on cardiovascular events such as strokes – meaning the full potential of the polypill has remained unclear. The latest study tackled both of these problems.

There has been a lot of talk about using this simple, fixed-dose combination drug for prevention of cardiovascular disease and I think we have shown that as a strategy it can work,” said Prof Tom Marshall, a co-author of the study from the University of Birmingham, adding that the pills might cost as little as a few pence per day. The new study involved more than 6,800 participants aged 50-75 from rural Iran – an area where almost 34% of premature deaths are down to coronary heart disease, and 14% are caused by strokes.

Writing in the Lancet, researchers from the UK, US and Iran reported that 3,417 people were given only minimum care, such as help with controlling blood pressure or cholesterol if needed, as well as lifestyle advice on topics such as diet, exercise and smoking. A similar number of people were, in addition to this, also given the polypill. More than 90% of those involved in the study did not have cardiovascular disease at the outset. Participants were followed up for five years. Over that time, 202 people taking the polypill had a major cardiovascular event, such as heart attack, heart failure, or stroke, compared with 301 in the “advice” group.

The authors say that translated as a 34% lower risk of having such an event, compared with the “advice” group, once factors including age, sex, diabetes and high blood pressure were taken into account.

There were also signs that, at least early on, the polypill reduced some aspects of high blood pressure, while it also led to a small fall in “bad” cholesterol. Both groups showed similar low levels of problematic events including internal bleeding and peptic ulcers. Overall, the results suggested that two major cardiovascular events would be avoided for every 69 people taking the tablet for 5 years. The polypill includes aspirin, which the team acknowledge is controversial as it can increase the risk of bleeding: the latest trial did not include people who were at high risk of such problems.

Source: https://www.theguardian.com/

Red-Blood-Cell “Hitchhikers” Transport Drugs to Specific Targets

A new drug-delivery technology which uses red blood cells (RBCs) to shuttle nano-scale drug carriers, called RBC-hitchhiking (RH), has been found in animal models to dramatically increase the concentration of drugs ferried precisely to selected organs, according to a study published in Nature Communications this month by researchers from the Perelman School of Medicine at the University of Pennsylvania. This proof-of-principle study points to ways to improve drug delivery for some of the nation’s biggest killers, such as acute lung disease, stroke, and heart attack.

The vast majority of drugs fail because they spread throughout the body, landing in nearby organs where they can cause intolerable side effects, as opposed to directly targeting the areas that are really in need,” said first author Jake Brenner, MD, PhD, an assistant professor of Pulmonary Medicine and Critical Care and of Pharmacology. “By massively increasing the drug concentrations that are hitting specific tissues, the RBC hitchhikers should decrease potential side effects and improve the efficacy of drugs delivered to target organs.”

The team showed that RH can safely transport nano-scale carriers of drugs to chosen organs by targeted placement of intravascular catheters, in mice, pigs, and in ex vivo human lungs, without causing RBC or organ toxicities.

Red blood cells are a particularly attractive carrier due to their biocompatibility and known safety in transfusions,” said senior author Vladimir Muzykantov, MD, PhD, a professor of Systems Pharmacology and Translational Therapeutics. “In just a few short years since we began this work, we are now on the brink of mapping out ways to test it in clinical trials.”

The researchers found that RH drug carriers injected intravenously increased drug uptake by about 40-fold in the lungs compared to absorption of freely circulating drug carriers in blood. In addition, injecting the RH drug carriers into the carotid artery (a major blood vessel in the neck that delivers blood to the brain, neck, and face) delivers 10 percent of the injected dose to the brain, which is about 10 times higher than what is achieved through older methods such using antibodies to guide drugs to their intended targets. Such impressive drug delivery to the brain could be used to treat acute strokes, the fourth leading cause of death in the U.S.

Development of RH technology has also revealed a potentially fundamental process that hold enormous clinical promise. “The body’s largest surface area of cell-to-cell interaction is observed between red blood cells and blood vessel linings, so it is intriguing to think that our RH technology has uncovered a phenomenon in which RBCs naturally transport cargo on their surfaces,” said Muzykantov.

Source: https://www.pennmedicine.org/