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mRNA technology: Vaccine biotech has helped repair broken hearts in mice



An illustration of a strand of mRNA

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Immune cells in the bodies of mice have been temporarily reprogrammed to repair damaged hearts by removing scar tissue, thanks to the technology used in the mRNA coronavirus vaccines.

“After you give the treatment, the scar goes away,” says Haig Aghajanian at the University of Pennsylvania.

Genetically engineered immune cells called CAR T-cells are already being used to treat cancer, but this is extremely expensive. The mRNA approach, which involves only temporarily modifying these cells, could dramatically decrease costs.

“CAR-T therapy has been a breakthrough, but it costs a lot,” says Aghajanian. “We’re hoping this is the next step in CAR-T-type technology that will allow more access. This type of thing you can get to developing countries, to remote areas.”

T-cells are immune cells that use receptors on their surface to recognise cells infected with viruses, which they then destroy. T-cells can be reprogrammed to target any desired cell type by giving them the appropriate receptor.

Conventional CAR T-cells are made by taking T-cells from a person’s body, genetically engineering them to add a gene for a “chimeric antigen receptor” – hence the name – and then returning them to that individual’s body. Such treatments can be very effective against cancers of the blood such as leukaemia, but producing the cells in a laboratory isn’t cheap. The first CAR-T treatment to get approved, called Kymriah, cost $475,000.

Aghajanian’s team is instead turning T-cells into CAR T-cells without removing them from the body, by delivering genes in the form of mRNAs. The mRNAs are packaged inside the same fatty balls, called lipid nanoparticles, as is used in the Pfizer/BioNTech and Moderna coronavirus vaccines.

In this case, however, the lipid nanoparticles have antibodies attached to them that bind to T-cells. The team had already been working on their research before the vaccines, but Aghajanian says the mass roll-out of vaccines should make it easier to get other uses of lipid nanoparticles approved by regulators

Some other teams have tried by create CAR T-cells inside the body by using viruses to permanently add DNA genes to the genomes of T-cells. This is potentially risky if something goes wrong.

mRNAs, by contrast, are temporary copies of genes used as templates by protein-making factories. They are not integrated into the genome and only persist for days. This means that adding mRNAs to T-cells doesn’t permanently alter them. In other words, it is a way of creating transient CAR T-cells. “It does its thing for a few days and then it is gone,” says Aghajanian.

His team has used this approach to target the cells that lay down collagen, which our bodies constantly produce, while other cells remove it. What happens after an injury is that the balance changes, because the cells that lay down collagen overproliferate, leading to a scar.

“They start putting down scar faster than other cells can take it up,” says Aghajanian. “If you can get rid of these cells, it goes back into balance and the scar quickly recedes.”

To test the method, his team damaged the hearts of mice in a way that creates a lot of scarring, or fibrosis. This makes the tissue stiffer and impairs the contraction and relaxation of the heart. Two weeks after the infusion of mRNA nanoparticles, the amount of scar tissue in the hearts of the mice was nearly halved of that in untreated animals, and their heart function improved significantly.

Besides treating injured hearts, the same approach might work for treating fibrosis of other organs including the kidney, liver and intestine, says Aghajanian. It might also be possible to treat scars on the skin with local injections. More generally, targeted delivery of mRNA to specific cells could be used to treat all kinds of diseases.

“It’s an encouraging demonstration that T-cells can be modified in vivo,” says Waseem Qasim at the Great Ormond Street Institute of Child Health in London, whose team is carrying out trials of CAR-T therapies.

Journal reference: Science, DOI: 10.1126/science.abm0594

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Solar storms may cause up to 5500 heart-related deaths in a given year



In an approximate 11-year cycle, the sun blasts out charged particles and magnetised plasma that can distort Earth’s magnetic field, which may disrupt our body clock and ultimately affect our heart


17 June 2022

A solar storm

Jurik Peter/Shutterstock

Solar storms that disrupt Earth’s magnetic field may cause up to 5500 heart-related deaths in the US in a given year.

The sun goes through cycles of high and low activity that repeat approximately every 11 years. During periods of high activity, it blasts out charged particles and magnetised plasma that can distort Earth’s magnetic field.

These so-called solar storms can cause glitches in our power grids and bring down Earth-orbiting satellites. A handful of studies have also hinted that they increase the risk of …

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UK Covid infection rate rising, with more than a million cases in England | Coronavirus



Coronavirus infections are rising in the UK, figures have revealed, with experts noting the increase is probably down to the more transmissible BA.4 and BA.5 Omicron variants.

The figures from the Office for National Statistics (ONS), based on swabs collected from randomly selected households, reveal that in the week ending 11 June an estimated one in 50 people in the community in England are thought to have had Covid – around 1.13 million people.

The figure is even higher, at one in 45, in both Wales and Northern Ireland, while it was highest in Scotland where, in the week ending 10 June, one in 30 people are thought to have been infected.

While the figures remain below the peak levels of infection seen earlier this year, when around one in 13 people in England had Covid, the findings are a rise on the previous week where one in 70 people in England were thought to be infected. Furthermore, the data reveals increases in all regions of England, except the north-east, and across all age groups.

Experts say that a key factor in the increase is probably the rise of the Covid variants of concern BA.4 and BA.5.

“Infections have increased across all four UK nations, driven by rising numbers of people infected with the BA.4 and BA.5 Omicron variants,” said Kara Steel, senior statistician for the Covid-19 Infection Survey.

While Steel said it remained too early to say if this was the start of another wave, others have warned it may already have begun, with increased mixing and travelling among other factors fuelling a rise in cases.

Among concerns scientists have raised are that BA.4, BA.5 and another variant on the rise, BA.2.12.1, replicate more efficiently in human lung cells than BA.2.

Prof Azra Ghani, an epidemiologist at Imperial College London, said the latest figures were not surprising, and might rise further.

“This increase in infection prevalence is likely due to the growth of the BA.4 and BA.5 Omicron subvariants, which as we have seen elsewhere in Europe, appear to be able to escape immunity generated from previous Omicron subvariants,” she said.

“It is therefore possible that we will continue to see some growth in infection prevalence in the coming weeks and consequently an increase in hospitalisations, although these subvariants do not currently appear to result in any significantly changed severity profile. This does however serve as a reminder that the Covid-19 pandemic is not over.”

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NHS to offer women in England drug that cuts recurrence of breast cancer | Breast cancer



Thousands of women in England with breast cancer are to benefit from a new pill on the NHS which reduces the risk of the disease coming back.

The National Institute for Health and Care Excellence (Nice) has given the green light to abemaciclib, which cuts the chance of breast cancer returning after a patient has had surgery to remove a tumour.

Trials showed that patients who had the drug with hormone therapy had a more than 30% improved chance of their cancer not coming back after surgery, compared with hormone therapy alone.

“It’s fantastic thousands of women with this type of primary breast cancer will now have an additional treatment option available on the NHS to help further reduce the risk of the disease coming back,” said Delyth Morgan, the chief executive of charity Breast Cancer Now.

“The fear of breast cancer returning or spreading to other parts of their body and becoming incurable can cause considerable anxiety for so many women and their loved ones.

“New effective treatments such as abemaciclib, which can offer more women the chance to further reduce the risk of the disease recurring, are therefore extremely welcome and this is an important step change in the drug options available for this group of patients.”

The twice-a-day pill is suitable for women with hormone receptor-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence who have had surgery. About 4,000 women will benefit initially, Nice said.

Helen Knight, the interim director of medicines evaluation at Nice, said the draft recommendation came less than a month after abemaciclib received its licence.

“The fact that we have been able to produce draft recommendations so quickly is testament to the success of our ambition to support patient access to clinically and cost effective treatments as early as possible,” said Knight. “Until now there have been no targeted treatments for people with this type of breast cancer.

“Abemaciclib with hormone therapy represents a significant improvement in how it is treated because being able to have a targeted treatment earlier after surgery will increase the chance of curing the disease and reduce the likelihood of developing incurable advanced disease.”

Abemaciclib works by targeting and inhibiting proteins in cancer cells which allow the cancer to divide and grow. It normally costs £2,950 for a packet of 56 150mg-tablets, but the manufacturer, Eli Lilly, has agreed an undisclosed discounted price for NHS England.

“Thanks in part to this latest deal struck by NHS England, NHS patients will be able to access another new targeted drug for a common and aggressive form of breast cancer,” said Prof Peter Johnson, the cancer director of NHS England.

“Abemaciclib, when used alongside a hormone therapy, offers a new, doubly targeted, treatment option, helping to increase the chances of beating the cancer for good, as well as meeting the NHS’s commitment to delivering improved cancer care under our long-term plan.”

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