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/

Milking Cow Cells in a Lab for Animal-Free Dairy

In a lab in Boston, a startup has spent the last few months cultivating mammary cells from a cow—and recently succeeded in finding the perfect conditions to get those cells to produce real cow milk without an animal.  “We spend a lot of time trying to understand how the biology works in a cow, and then trying to do that,” says Sohail Gupta, CEO and cofounder of the startup, called Brown Foods, which makes a product that it calls UnReal Milk.

The startup, which operates in India and the U.S., just completed a stint at the tech accelerator Y Combinator. Alternative-dairy sales keep growing: In 2020, according to the most recent data available, sales of oat, soy, almond, and other alt-milk products made up 15% of all milk sales in the U.S., a 27% growth over the previous two years. But Brown Foods, like others in the space, recognized that plant-based milk still can’t replicate traditional dairy.

They’re not yet there in terms of taste and texture,” Gupta says. They also often have less protein and other nutrients. He argues that other new milk alternatives, including those that use precision fermentation to make animal-free dairy proteins, also can’t perfectly match dairy since they still use plant ingredients for fat and other components. There are multiple reasons to move away from traditional dairy, including the fact that cows raised for milk and meat are responsible for around 30% of the world’s emissions of methane,a potent greenhouse gas. But Gupta thinks that it makes sense to stay as close to the natural process as possible. Mammary cells “have evolved naturally over centuries to produce milk in mammals,” he says. “So these cells have the entire genetic architecture to produce the fats, the carbs, the proteins.

The company’s biochemical engineers have been studying how the cells behave, what they need nutritionally to survive, and what triggers lactation. “We’re trying to emulate nature and understand what kind of chemical signals are released in a mammal to trigger the cells to lactate and start secreting milk and get into the lactation phase,” he says. Now that they’ve shown that it can work at the small scale in the lab, they’re beginning to prepare for commercial production in larger bioreactors. The company believes that it can eventually reach price parity with conventional milk. In early calculations, it says that it could cut the greenhouse gas emissions from milk by 90%. (Unlike lab-grown meat, which requires an energy-intensive process of growing cells, producing milk just requires keeping cells alive, and has a far smaller footprint.)

Source: https://www.fastcompany.com/

27 Proteins that May Predict Heart Disease Risk

In a new study, scientists have reported findings that show a blood test can be used to predict Cardiac Vascular Disease (CVD). The research, published in the journal Science Translational Medicine, opens the door to more individualized treatment plans for CVD. It may also improve the speed at which new CVD drugs can be identified and developed. When a new drug is developed, scientists have to make sure that it is both effective and safe. This is a rigorous process that can often take many years. While important, this significantly slows down the speed at which new drugs can be developed, and also increases the costs.

One way of increasing the speed and reducing the cost of drug development without sacrificing efficacy or safety is to use a surrogate biomarker as a predictor of risk. If a surrogate can reliably predict risk, then some stages of clinical trials can be streamlinedFinding a surrogate that can accurately predict the risk of certain diseases can also benefit patients directly. If a clinician can measure a reliable surrogate they can potentially prevent a disease before it has developed, reducing the risks to the patient.

For situations where clinical cardiovascular outcomes studies are required today, a surrogate enables unsafe or ineffective candidate drugs to be terminated early and cheaply and supports the acceleration of safe and effective drugs. Participants in the trials do not have to have events or die in order to contribute to the signal.” said Dr. Stephen Williams — Chief Medical Officer at SomaLogic, and the corresponding author of the present study. “In personalized medicine, a surrogate enables cost-effective allocation of treatments to the people who need them the most, and potentially increases the uptake of newer more effective drugs so that outcomes are improved,” said Dr. Williams.

In 2004 the United States Food and Drug Administration (FDA) published a report Trusted Source recommending that researchers identify biomarker surrogates that could help in CVD drug development and improve individualized patient care.

Nano-Robots Injected into your Bloodstream to Fight Disease

What if there was a magical robot that could cure any disease? Don’t answer that. It’s a stupid question. Everyone knows there’s no one machine that could do that. But maybe a swarm made up of tens of thousands of tiny autonomous micro-bots could? That’s the premise laid out by proponents of nanobot medical technology. In science fiction, the big idea usually involves creating tiny metal robots via some sort of magic-adjacent miniaturization technology.

Luckily for us, the reality of nanobot tech is infinitely cooler. A team of researchers from Australia have developed a mind-blowing prototype that could work as a proof-of-concept for the future of medicine. Called “autonomous molecular machines,” the new nanotechnology eschews the traditional visage of microscopic metal automatons in favor of a more natural approach.

Inspired by biology, we design and synthesize a DNA origami receptor that exploits multivalent interactions to form stable complexes that are also capable of rapid subunit exchange”, explained the researchers. “DNA nanobots are synthetic nanometer-sized machines made of DNA and proteins. They’re autonomous because DNA itself is a self-assembling machine. Our natural DNA not only carries the code our biology is written in, it also knows when to execute. That’s part of the reason why, for example, your left and right feet tend to grow at roughly the same rate.”

Previous work in the field of DNA nanotechnology has demonstrated self-assembling machines capable of transferring DNA code, much like their natural counterparts. But the new tech out of Australia is unlike anything we’ve ever seen before.
Using the DNA origami receptor to demonstrate stable interactions with rapid exchange of both DNA and protein subunits, thus highlighting the applicability of the approach to arbitrary molecular cargo, an important distinction with canonical toehold exchange between single-stranded DNA. These particular nanobots can transfer more than just DNA information. Theoretically speaking, they could deliver any conceivable combination of proteins throughout a given biological system. To put that in simpler terms: the scientists should be able to eventually program swarms of these nanobots to hunt down bacteria, viruses, and cancer cells inside of our bodies. Each member of the swarm could carry a specific protein and, when they’ve found a bad cell, they could assemble their proteins into a formation designed to eliminate the threat.

Source: https://thenextweb.com/

Two Studies Assess Pfizer’s Effectiveness Against Omicron

The Omicron variant substantially reduced antibody levels generated by the Pfizer-BioNTech COVID-19 vaccine, according to preliminary results from a South African study that’s still awaiting peer review. These are the first laboratory results to see how a COVID-19 vaccine holds up to Omicron. A team of researchers led by Africa Health Research Institute‘s Alex Sigal tested 14 blood samples from 12 people against a live sample of the Omicron variant. All 12 people were vaccinated, and six were previously infected.

Overall, the scientists found a roughly 40-fold reduction in the levels of neutralizing antibodies, the virus-fighting proteins that play a key role in our immune response, compared with the original version of the virus. Omicron did not evade vaccine protection completely, Sigal wrote on Twitter, meaning there’s still benefit to being vaccinated against this new variant. But the marked reduction in antibodies raises questions of how durable vaccine protection will be against Omicron – namely, whether booster shots will sufficiently ward off disease or if new vaccines may eventually be required. Sigal called it a “very large drop in neutralization of Omicron.”

A good booster probably would decrease your chance of infection, especially severe infection leading to more severe disease,” Sigal said in an online presentation of his results on Tuesday, according to Bloomberg. “People who haven’t had a booster should get one, and people who have been previously infected should be vaccinated.”

Shortly after Sigal announced his team’s results, another group of researchers at Sweden‘s Karolinska Institutet disclosed their own findings that suggested a substantial but less dramatic decline in antibody levels. The Karolinska team found a seven-fold reduction across 17 blood samples. They noted the impact of Omicron varied greatly between samples, and they used a version of Omicron that was artificially made in a lab instead of the live virus. A lead researcher for that group said the findings make Omicron “certainly worse than Delta, but, again, not as extreme as we expected.” The results are not finalized and have not been published in a medical journal. Sigal cautioned on Twitter that the findings “are likely to be adjusted as we do more experiments.”

Source: https://www.sciencealert.com/

DNA Is Not the Only Mode of Biological Inheritance

A little over a decade ago, a clutch of scientific studies was published that seemed to show that survivors of atrocities or disasters such as the Holocaust and the Dutch famine of 1944-45 had passed on the biological scars of those traumatic experiences to their children.

The studies caused a sensation, earning their own BBC Horizon documentary and the cover of Time – and no wonder. The mind-blowing implications were that DNA wasn’t the only mode of biological inheritance, and that traits acquired by a person in their lifetime could be heritable. Since we receive our full complement of genes at conception and it remains essentially unchanged until our death, this information was thought to be transmitted via chemical tags on genes called “epigenetic marks” that dial those genes’ output up or down. The phenomenon, known as transgenerational epigenetic inheritance, caught the public imagination, in part because it seemed to release us from the tyranny of DNA. Genetic determinism was dead.

A model of DNA methylation – the process that modulates genes. The influence of environment or lifestyle on this process is being studied

A decade on, the case for transgenerational epigenetic inheritance in humans has crumbled. Scientists know that it happens in plants, and – weakly – in some mammals. They can’t rule it out in people, because it’s difficult to rule anything out in science, but there is no convincing evidence for it to date and no known physiological mechanism by which it could work. One well documented finding alone seems to present a towering obstacle to it: except in very rare genetic disorders, all epigenetic marks are erased from the genetic material of a human egg and sperm soon after their nuclei fuse during fertilisation. “The [epigenetic] patterns are established anew in each generation,” says geneticist Bernhard Horsthemke of the University of Duisburg-Essen in Germany.

Different people define epigenetics differently, which is another reason why the field is misunderstood. Some define it as modifications to chromatin, the package that contains DNA inside the nuclei of human cells, while others include modifications to RNA. DNA is modified by the addition of chemical groups. Methylation, when a methyl group is added, is the form of DNA modification that has been studied  most, but DNA can also be tagged with hydroxymethyl groups, and proteins in the chromatin complex can be modified too.

Researchers can generate genome-wide maps of DNA methylation and use these to track biological ageing, which as everyone knows is not the same as chronological ageing. The first such “epigenetic clocks” were established for blood, and showed strong associations with other measures of blood ageing such as blood pressure and lipid levels. But the epigenetic signature of ageing is different in different tissues, so these couldn’t tell you much about, say, brain or liver. The past five years have seen the description of many more tissue-specific epigenetic clocks.

Mill’s group is working on a brain clock, for example, that he hopes will correlate with other indicators of ageing in the cortex. He has already identified what he believes to be an epigenetic signature of neurodegenerative disease. “We’re able to show robust differences in DNA methylation between individuals with and without dementia, that are very strongly related to the amount of pathology they have in their brains,” Mill says. It’s not yet possible to say whether those differences are a cause or consequence of the pathology, but they provide information about the mechanisms and genes that are disrupted in the disease process, that could guide the development of novel diagnostic tests and treatments. If a signal could be found in the blood, say, that correlated with the brain signal they’ve detected, it could form the basis of a predictive blood test for dementia.

Source: https://www.theguardian.com/

White Blood Cells May Be Harnessed To Boost Cancer Immunotherapy

White blood cells called eosinophils can be “summoned” in order to fight cancer by both destroying the cancer cells directly as well as recruiting the immune system’s cancer-fighting T-cells, according to a new study published in the journal of the American Association for Cancer Research.

Eosinophils produce powerful destructive proteins intended for fighting parasites. However, in the modern Western world, where high levels of hygiene have significantly reduced the risk of many parasites, eosinophils can be harmful, inducing allergies and asthma. Considering the destructive power of eosinophils, the researchers decided to test the potential benefits of these white blood cells if turned against cancer cells.

Examining tissue samples of lung metastases taken from breast cancer patients, the researchers found that eosinophils reach the lungs and penetrate cancerous tissues, where they often release their destructive proteins and summon T-cells for reinforcement. Ultimately, T-cells gather in the affected lungs, slowing the growth of tumors. In the absence of eosinophils, lung metastases were much larger than those exposed to the white blood cells. These findings led to the conclusion that eosinophils could serve as a basis for improved immunotherapeutic medications to fight cancer effectively.

An eosinophil, a type of white blood cell. A new study shows these cells can be “summoned” to fight cancer

We chose to focus on lung metastases for two main reasons. First, metastases, and not the primary tumors, are often the main problem in treating cancer, and the lungs are a major target for the metastasis of many types of cancer,” said lead researcher, professor Ariel Munitz of Tel Aviv University’s department of microbiology and clinical immunology.
Second, in a preliminary study we demonstrated that eosinophils gather in tumors developing in mucous tissues like the lungs, and therefore assumed that they would be found in lung metastases as well,”  he said.  Compared to traditional techniques, immunotheraphy generally leads to longer protection from cancer and fewer side effects. This new discovery may contribute to the development of new methods of immunotherapy. “Enhancing the number and power of T-cells is one of the main targets of immunotherapy treatments administered to cancer patients today,” said Munitz.

Source: https://www.zenger.news

How to Use mRNA Technology in Vaccines to Fight Cancer

Until recently, most of the world had never heard of mRNA vaccines. To combat COVID-19, the United States Food and Drug Administration issued emergency use authorization in December 2020 for mRNA vaccines developed by Pfizer-BioNTech and Moderna. While the pandemic brought mRNA vaccines into the limelight, melanoma patient Bobby Fentress had experience with mRNA technology nearly a year prior. mRNA vaccines hold promise for fighting infectious diseases beyond the SARS-CoV-2 virus, including fighting cancer. At age 68, Bobby was an early participant in a clinical trial intended to see whether a vaccine made with mRNA could destroy his cancer cells and prevent recurrence.

Bobby’s story began in 2019. He found an odd bump on his middle finger and assumed it was a wart. After his wife urged him to be seen by a dermatologist, he received a call that he would need a biopsy – which ultimately revealed that he had stage 2c melanoma. Several months later, Bobby had most of his middle finger amputated and was told that there was a 50% possibility that the cancer would reoccur.  That’s when Bobby decided to enroll in a clinical trial with HCA Healthcare’s Sarah Cannon Research Institute in Nashville, Tennessee. He received his first shots of a personalized mRNA vaccine created by Moderna in April 2020. These vaccines are developed from a patient’s specific tumor DNA. The DNA of the tumor is analyzed to determine the differences between the tumor and a patient’s own cells and which proteins might elicit the best immune response. The mRNA vaccine is then developed to instruct the body to make these proteins and stimulate an immune response. Patients such as Bobby then receive a series of these vaccine treatments.

Bobby finished his year of treatment earlier this spring. While it is too early to know if the therapy will work, Bobby’s oncologist, Dr. Meredith McKean, is optimistic.  Immunotherapy has been a game changer for melanoma. With mRNA, the hope is that personalized therapy would offer additional treatment benefit above our standard treatments that we offer for patients broadly. Even for patients like Bobby that had surgery, ten years ago we wouldn’t be able to give him anything but highly toxic therapy options. It’s refreshing to offer a clinical trial like this. While the trial is not yet complete, we have enough data to be hopeful. It’s a very encouraging area that I’m excited about as a provider,” says Dr McKean, associate director of the melanoma and skin cancer research program at Sarah Cannon Research Institute.

https://hcahealthcaretoday.com/

Jeff Bezos and Yuri Milner fund anti-aging start-up

Billionaires Jeff Bezos an Yuri Milner are reportedly funding a startup biotechnology firm with the aim of discovering a way to reverse aging.  Altos Labs was incorporated in the US and the UK earlier this year, and has raised at least $270million to look into the potential of cell reprogramming technology to turn back the clock in animals, and potentially, humans.

While little is known so far about Altos, early hires give an indication of the kinds of anti-aging techniques the lab might be looking into. They include Dr. Shinya Yamanaka, who pioneered researched into cell reprogramming, earning him the 2012 Nobel Prize for the research. He discovered that by adding just four specific proteins to cells, they can be instructed to revert back into an earlier state with the properties of embryonic stem cells that make up building blocks of new animal life.

He will serve as an unpaid advisor on Altosscientific advisory board, according to MIT Technology Review, which reported on Altos’ formation.

Source:  https://www.dailymail.co.uk/

Our Bodies Age in 3 Distinct Shifts

The carnival worker who tries to guess your age relies on aspects of your appearance, such as your posture and whether any wrinkles emanate from the corners of your eyes and lips. If the carny’s guess is more than a few years off, you win a stuffed koala.

But a team of Stanford University School of Medicine scientists doesn’t need to know how you look to guess your age. Instead, it watches a kind of physiological clock: the levels of 373 proteins circulating in your blood. If the clock is off, you don’t win a plush toy. But you may find out important things about your health.

We’ve known for a long time that measuring certain proteins in the blood can give you information about a person’s health status — lipoproteins for cardiovascular health, for example,” said Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, the D. H. Chen Professor II and co-director of the Stanford Alzheimer’s Disease Research Center. “But it hasn’t been appreciated that so many different proteins’ levels — roughly a third of all the ones we looked at — change markedly with advancing age.

Changes in the levels of numerous proteins that migrate from the body’s  tissues into circulating blood not only characterize, but quite possibly cause, the phenomenon of aging, Wyss-Coray said. A paper describing the research was published Dec. 5 in Nature Medicine. Wyss-Coray is the senior author. The lead author is neurology instructor Benoit Lehallier, PhD.

The researchers analyzed plasma — the cell-free, fluid fraction of blood — from 4,263 people ages 18-95. “Proteins are the workhorses of the body’s constituent cells, and when their relative levels undergo substantial changes, it means you’ve changed, too,” Wyss-Coray said. “Looking at thousands of them in plasma gives you a snapshot of what’s going on throughout the body.”

The study’s results suggest that physiological aging does not simply proceed at a perfectly even pace, but rather seems to chart a more herky-jerky trajectory, with three distinct inflection points in the human life cycle. Those three points, occurring on average at ages 34, 60 and 78, stand out as distinct times when the number of different blood-borne proteins that are exhibiting noticeable changes in abundance rises to a crest. This happens because instead of simply increasing or decreasing steadily or staying the same throughout life, the levels of many proteins remain constant for a while and then at one point or another undergo sudden upward or downward shifts. These shifts tend to bunch up at three separate points in a person’s life: young adulthood, late middle age and old age.

The investigators built their clock by looking at composite levels of proteins within groups of people rather than in individuals. But the resulting formula proved able to predict individuals’ ages within a range of three years most of the time. And when it didn’t, there was an interesting upshot: People whose predicted age was substantially lower than their actual one turned out to be remarkably healthy for their age.

The researchers obtained their samples from two large studies. One of them, known as the LonGenity study, has assembled a registry of exceptionally long-lived Ashkenazi Jews. It was able to provide many blood samples from people as old as 95. On measuring the levels of roughly 3,000 proteins in each individual’s plasma, Wyss-Coray’s team identified 1,379 proteins whose levels varied significantly with participants’ age.

Source: https://med.stanford.edu/
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