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/

Scientists Have Possibly Cured HIV

An American research team reported that it has possibly cured HIV in a woman for the first time. Building on past successes, as well as failures, in the HIV-cure research field, these scientists used a cutting-edge stem cell transplant method that they expect will expand the pool of people who could receive similar treatment to several dozen annually.

Their patient stepped into a rarified club that includes three men whom scientists have cured, or very likely cured, of HIV. Researchers also know of two women whose own immune systems have, quite extraordinarily, apparently vanquished the virus. Carl Dieffenbach, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, one of multiple divisions of the National Institutes of Health that funds the research network behind the new case study, told NBC News that the accumulation of repeated apparent triumphs in curing HIV “continues to provide hope.”

It’s important that there continues to be success along this line,” he said.

In the first case of what was ultimately deemed a successful HIV cure, investigators treated the American Timothy Ray Brown for acute myeloid leukemia, or AML. He received a stem cell transplant from a donor who had a rare genetic abnormality that grants the immune cells that HIV targets natural resistance to the virus. The strategy in Brown’s case, which was first made public in 2008, has since apparently cured HIV in two other people. But it has also failed in a string of others. This therapeutic process is meant to replace an individual’s immune system with another person’s, treating their cancer while also curing their HIV. First, physicians must destroy the original immune system with chemotherapy and sometimes irradiation. The hope is that this also destroys as many immune cells as possible that still quietly harbor HIV despite effective antiretroviral treatment. Then, provided the transplanted HIV-resistant stem cells engraft properly, new viral copies that might emerge from any remaining infected cells will be unable to infect any other immune cells.

Source: https://www.nbcnews.com/

HIV Vaccine Uses mRNA technology

An experimental HIV vaccine that uses the same technology as the COVID-19 mRNA vaccines from Moderna and Pfizer is showing promising results in both monkeys and mice. A press release from the National Institute of Allergy and Infectious Diseases (NIAID) explained that monkeys who received a multiple doses of the experimental vaccine had their chances of contracting an HIV-like virus lowered by 79%.

Scientists have spent decades struggling to create an HIV vaccine due to the speed at which the virus mutates and its remarkable ability to evade the immune system. Dr. Anthony Fauci, president of NIAID, leader of the United States’ battle against COVID-19, and a co-author of this HIV vaccine study published in Nature Medicine, expressed optimism about the progress made by the mRNA technology.

Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains an elusive goal,” Fauci said. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.”

The trial involved a series of booster shots in macaques over the course of an entire year. The authors explained that not only did the trial yield a positive immune response, but also that “the vaccine was well tolerated with only mild adverse events after each inoculation,” with the most common side effect being loss of appetite.

Now the researchers are working on refining the process so less rounds of shots are needed, as they noted in Nature Medicine that “a vaccination regimen encompassing seven or more sequential immunizations would be difficult to implement in humans.” The study’s leader Dr. Paolo Lusso, said that if the team is successful at reducing the number of boosters in a safe and effective way, they will then move on to a phase 1 trial of the vaccine in adult humans.

Source: https://www.lgbtqnation.com/

mRNA Vaccines will Soon Prevent Cancer

In the early 1990s, mRNA technology emerged as an alternative to traditional vaccine development, building on research conducted by Wolff et al. involving direct gene transfer into mouse muscle in vivo. Initially, mRNA technology came with drawbacks as it caused severe inflammation upon administration, degraded quickly in the body and was difficult to move across the membrane into the cell. However, breakthroughs using nanotechnology overcame some of these challenges; scientists encased the RNA and used synthetic RNA that the body’s immune system recognizes.

Other major technological innovation and research investment has improved the delivery, translation and stability, enabling mRNA to become a promising tool for vaccine development. These breakthroughs have allowed further research and development of mRNA vaccines, particularly against viruses such as HIV and influenza. In 2020, when the COVID-19 pandemic hit, several human clinical trials were underway to test mRNA vaccines against influenza and HIV. As a result of the pandemic, research efforts, funding and facilities prioritized the development of mRNA vaccines for COVID-19. Combined efforts of global research teams working on COVID-19 mRNA vaccinations accelerated the field of research, improving the knowledge, understanding and methods of mRNA vaccine technology. This allowed the progression of mRNA vaccines for other diseases, such as cancer, and clinical trials for mRNA cancer vaccinations are now underway. The MD Anderson Cancer Center (TX, USA) is conducting a clinical trial to test whether mRNA technology can be used to prevent the recurrence of colorectal cancer.


A B cell displays antibodies specific to antigens on a colorectal cancer cell and signals killer T cells to destroy it.

People with colorectal cancer often undergo surgery to remove the cancerous tumor; however, cancer cells remain in the body and shed DNA into the bloodstream, which is known as circulating tumor DNA (ctDNA) and can cause further complications and metastasis. Van Morris and Scott Kopetz are leading the Phase II trial (NCT04486378) for a personalized mRNA cancer vaccine. People who have stage II or III colorectal cancer are given a blood test after their surgery to check for ctDNA. The patient’s tumor tissue is genetically profiled to identify mutations that fuel cancer growth. The tumor mutations are then ranked from the most to the least common to create a personalized mRNA vaccine for the patient. “We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient,” explains Morris.

Source: https://www.future-science.com/

Moderna to Trial HIV and Flu Vaccines With mRNA Technology

The astonishing success of COVID-19 vaccines may signal a breakthrough in disease prevention technologyModerna is developing influenza and HIV vaccines using mRNA technology, the backbone of its effective COVID-19 vaccine. The biotech company is expected to launch phase 1 trials for its mRNA flu and HIV vaccines this year. If successful, mRNA may offer a silver lining to the decades-long fight against HIV, influenza, and other autoimmune diseases. Traditional vaccines often introduce a weakened or inactive virus to one’s body. In contrast, mRNA technology uses genetic blueprints, which build proteins to train the immune system to fight off the virus. Since mRNA teaches the body to recognize a virus, it can be effective against multiple strains or variants as opposed to just one.

The mRNA platform makes it easy to develop vaccines against variants because it just requires an update to the coding sequences in the mRNA that code for the variant,”  said Rajesh Gandhi, MD, an infectious diseases physician at Massachusetts General Hospital and chair of HIV Medicine association.

Future mRNA vaccines have the potential to ward off multiple diseases with one shot, according to the Centers for Disease Control and Prevention (CDC).  Current mRNA vaccines, as demonstrated in their use against COVID-19, already appear to be less susceptible to new variants. “Based on its success in protecting against COVID-19, I am hopeful that mRNA technology will revolutionize our ability to develop vaccines against other pathogens, like HIV and influenza,” Gandhi says.

Moderna’s flu and HIV vaccines are still in early development stages, having yet to undergo their clinical trials. Still, if they prove successful, the mRNA-based treatment could dramatically change health care — both in expediting the route to immunity and by providing a solution to illnesses that have been around for decades. Scientists currently make annual alterations to the typical flu shot to keep up with the viruses in circulation. But a successful mRNA vaccine could provide a far more effective alternative.

An approved mRNA flu vaccine could be administered every other year rather than annually, explained virologist Andrew Pekosz, PhD. This is because mRNA accounts for variants and produces a stronger and longer-lasting immune response than that of the current flu vaccine, he says. The influenza vaccine is similar to the COVID-19 vaccine because the viruses have similar characteristics and necessary treatments, according to Pekosz.

However, a potential concern lies in the level of public immunity prior to receiving a vaccine. Since the flu has been around since the early 1900s, an mRNA vaccine could potentially boost older or less effective antibody responses rather than targeting current strains, Pekosz adds. “There’s no way to answer that question except to do some clinical trials, and see what the results tell us”.

Source: https://www.verywellhealth.com/

1st Long-acting HIV Drug Combo

U.S. regulators have approved the first long-acting drug combo for HIV, monthly shots that can replace the daily pills now used to control infection with the AIDS virus. The approval of the two-shot combo called Cabenuva is expected to make it easier for people to stay on track with their HIV medicines and to do so with more privacy. It’s a huge change from not long ago, when patients had to take multiple pills several times a day, carefully timed around meals.

That will enhance quality of life” to need treatment just once a month, said Dr. Steven Deeks, an HIV specialist at the University of California, San Francisco, who has no ties to the drug’s makers. “People don’t want those daily reminders that they’re HIV infected.”

Cabenuva combines rilpivirine, sold as Edurant by Johnson & Johnson’s Janssen unit, and a new drug — cabotegravir, from ViiV Healthcare. They’re packaged together and given as separate shots once a month. Dosing every two months also is being tested.

The U.S. Food and Drug Administration approved Cabenuva for use in adults who have had their disease well controlled by conventional HIV medicines and who have not shown signs of viral resistance to the two drugs in Cabenuva. The agency also approved a pill version of cabotegravir to be taken with rilpivarine for a month before switching to the shots to be sure the drugs are well toleratedViiV said the shot combo would cost $5,940 for an initial, higher dose and $3,960 per month afterward. The company said that is “within the range” of what one-a-day pill combos cost now. How much a patient pays depends on insurance, income and other things. Studies found that patients greatly preferred the shots.

Even people who are taking one pill once a day just reported improvement in their quality of life to switch to an injection,” said Dr. Judith Currier, an HIV specialist at the University of California, Los Angeles. She consults for ViiV and wrote a commentary accompanying one study of the drug in the New England Journal of Medicine. Deeks said long-acting shots also give hope of reaching groups that have a hard time sticking to treatment, including people with mental illness or substance abuse problems. “There’s a great unmet need” that the shots may fill, he said.

Source: https://www.pbs.org/

COVID: the Risk of Death is 70% Higher for Male than for Female Patients

Evidence increasingly indicates that male sex is a risk factor for more severe disease and death from COVID-19. Male bias in COVID-19 mortality is observed in nearly all countries with available sex-disaggregated data, and the risk of death in males is ∼1.7 times higher than in females. Aging is strongly associated with higher risk of death in both sexes, but at all ages above 30 years, males have a significantly higher mortality risk, rendering older males the most vulnerable group. Sex differences are intertwined with differences in gender roles socially and with behavioral factors, which also influence COVID-19 incidence and outcomes. However, there are also possible biological mechanisms of male sex bias that affect the severity of COVID-19, particularly with respect to immune responses.

Sex differences beyond sex organs are present across species and extend to physiological systems, including the immune system. Infection by different pathogens results in differential immune responses and disease outcomes by sex, and although the pattern depends on age and other host factors, male sex is more often associated with lower immune responses and higher susceptibility and/or vulnerability to infections in animals. This is generally also the case in humans: Male patients have higher viral loads for hepatitis B virus (HBV) and HIV. Conversely, females generally mount a more robust immune response to vaccines, such as influenza vaccines. However, the heightened immune responses in females can also lead to detrimental immunopathology in infections.

The physiological response to virus infection is initiated when virus replication is detected by pattern recognition receptors. This leads to two antiviral programs by the infected cells.
Source: https://science.sciencemag.org/

Experimental Treatment May Have Eliminated Man’s HIV

A Brazilian man infected with the AIDS virus has shown no sign of it for more than a year since he stopped HIV medicines after an intense experimental drug therapy aimed at purging hidden, dormant virus from his body, doctors reported Tuesday. The case needs independent verification and it’s way too soon to speculate about a possible cure, scientists cautioned.

These are exciting findings but they’re very preliminary,” said Dr. Monica Gandhi, an AIDS specialist at the University of California, San Francisco (UCSF).This has happened to one person, and one person only,” and it didn’t succeed in four others given the same treatment, she said.

Another UCSF specialist, Dr. Steven Deeks, said: “This is not a cure,” just an interesting case that merits more study.

The case was described at an AIDS conference where researchers also disclosed an important prevention advance: A shot of an experimental medicine every two months worked better than daily Truvada pills to help keep uninfected gay men from catching HIV from an infected sex partner. Hundreds of thousands of people take these “pre-exposure prevention” pills now and the shot could give a new option, almost like a temporary vaccine.

If the Brazil man’s case is confirmed, it would be the first time HIV has been eliminated in an adult without a bone marrow or stem cell transplant. Independent experts want to see whether his remission lasts and for the intense drug combination that he received to undergo more testing.

I’m very moved because it’s something that millions of people want,” said the 35-year-old man, whose spoke to The Associated Press on condition that his name not be published. “It’s a gift of life, a second chance to live.

Source: https://www.nbcnews.com/

“Shock And Kill” Strategy To Eliminate HIV

When therapeutics battle HIV, they tend to miss pockets of resistance where HIV can hunker down until it stages a comeback. HIV, then, cannot be defeated until its remnants are roused to action, and its hiding places exposed and eliminated. This two-step strategy is called “shock and kill.” It sounds promising, but shock and kill hasn’t quite worked yet. It still needs the right shock.

Encouragingly, a better shock has been proposed by scientists at Sanford Burnham Prebys Medical Discovery Institute. These scientists, led by Sumit Chanda, PhD, director and professor and Nicholas Cosford, PhD, deputy director of the NCI-designated Cancer Center at Sanford Burnham Prebys and co-senior author of the study, have identified a drug that reawakens the virus without activating the immune system. That is, the drug makes it possible to save the immune system without having to destroy it.

What scientists have found with other ‘shock’ approaches is that they can be too hot and overactivate the immune system, or too cold and don’t wake up the virus,” said Chanda. “Our research identifies a drug that works in the ‘Goldilocks’ zone.”

The drug is a Smac mimetic called Ciapavir (SBI-0953294). Smac mimetics are a class of small-molecule peptidomimetics derived from a conserved binding motif of Smac (second mitochondria-derived activator of caspases), an endogenous protein inhibitor of apoptosis. Originally developed as cancer drugs, Smac mimetics are being evaluated for other purposes, such as fighting HIV.

Repurposed Smac mimetics have had modest success in reversing HIV latency. In hopes of building on this success, Chanda, Cosford, and colleagues decided to experiment with a Smac mimetic optimized to reverse HIV latency. The results of this work appeared June 23 in Cell Reports Medicine, in an article titled, “Pharmacological Activation of Non-canonical NF-κB Signaling Activates Latent HIV-1 Reservoirs In Vivo.” According to this article, Ciapavir is more efficacious as a latency-reversing agent than other drugs of its class.

Ciapavir induced activation of HIV-1 reservoirs in vivo in a bone marrow, liver, thymus (BLT) humanized mouse model without mediating systemic T cell activation,” the article’s authors wrote. “This study provides proof of concept for the in vivo efficacy and safety of Ciapavir and indicates that Smac mimetics can constitute a critical component of a safe and efficacious treatment strategy to eliminate the latent HIV-1 reservoir.”

Source: https://www.genengnews.com/

Coronavirus Uses Same Strategy As HIV To Dodge Immune Response

The novel coronavirus uses the same strategy to evade attack from the human immune system as HIV, according to a new study by Chinese scientists.

Both viruses remove marker molecules on the surface of an infected cell that are used by the immune system to identify invaders, the researchers said in a non-peer reviewed paper posted on preprint website bioRxiv.org on Sunday. They warned that this commonality could mean Sars-CoV-2, the clinical name for the virus, could be around for some time, like HIV.

Virologist Zhang Hui and a team from Sun Yat-sen University in Guangzhou also said their discovery added weight to clinical observations that the coronavirus was showing “some characteristics of viruses causing chronic infection”.

Their research involved collecting killer T cells from five patients who had recently recovered from Covid-19, the disease caused by the virus. Those immune cells are generated by people after they are infected with Sars-CoV-2 – their job is to find and destroy the virus.

The molecule is an identification tag usually present in the membrane of a healthy cell, or in sick cells infected by other coronaviruses such as severe acute respiratory syndrome, or Sars. It changes with infections, alerting the immune system whether a cell is healthy or infected by a virusHIV uses the same strategyMHC molecules are also absent in cells infected with that virusIn contrast, Sars does not make use of this function,” Zhang said.

The coronavirus removes these markers by producing a protein known as ORF8, which binds with MHC molecules, then pulls them inside the infected cell and destroys them, the researchers said. ORF8 is known to play an important role in viral replication, and most commercial test kits target this gene to detect viral loads in nose or oral swabs.

While drugs being used to treat Covid-19 patients mainly targeted enzymes or structural proteins needed for viral replication, Zhang and his team suggested compounds be developedspecifically targeting the impairment of MHC by ORF8, and therefore enhancing immune surveillance for Sars-CoV-2 infection”.

Source: https://www.scmp.com/