Simple Eye Test Uses AI To Predict Death From a Heart Condition

A simple eye test that predicts death from cardiovascular disease has been developed by British scientists. It combines artificial intelligence (AI) with scans of the retina – a membrane at the back of peepers that contains light sensitive cells. The technique could lead to a screening programme – enabling drugs and lifestyle changes to be prescribed decades before symptoms emerge. Lead author Professor Alicja Regina Rudnicka, of St George’s University of London, said the test is inexpensive, accessible and non-invasive. People at risk of stroke, heart attack and other circulatory conditions could undergo RV (artificial intelligence enabled retinal vasculometry) during routine visits to the optician.

Prof Rudnicka said: “It has the potential for reaching a higher proportion of the population in the community because of ‘high street’ availability. “RV offers an alternative predictive biomarker to traditional risk-scores for vascular health – without the need for blood sampling or blood pressure measurement. “It is highly likely to help prolong disease-free status in an ever-aging population with increasing comorbidities, and assist with minimising healthcare costs associated with lifelong vascular diseases.”

An algorithm called QUARTZ was developed based on retinal images from tens of thousands of Britons aged 40 to 69. It focused on the width, area and curvature, or tortuosity, of tiny blood vessels called arterioles and venules. The performance of QUARTZ was compared with the widely used Framingham Risk Scores framework – both separately and jointly.

The health of all the participants was tracked for an average of seven to nine years, during which time there were 327 and 201 circulatory disease deaths among 64,144 UK Biobank and 5,862 EPIC-Norfolk participants respectively. In men, arteriolar and venular width, tortuosity, and width variation emerged as important predictors of death from circulatory disease. In women, arteriolar and venular area and width and venular tortuosity and width variation contributed to risk prediction.

The predictive impact of retinal vasculature on circulatory disease death interacted with smoking, drugs to treat high blood pressure, and previous heart attacks. Overall, these predictive models, based on age, smoking, medical history and retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk.

Source: https://www.mirror.co.uk/

Dissolving Implantable Device Relieves Pain Without Drugs

A Northwestern University-led team of investigators has developed a small, soft, flexible implant that relieves pain on demand and without the use of drugs. Described in a study published in Science, the first-of-its-kind device could provide a much-needed alternative to opioids and other highly addictive medications.

The biocompatible, water-soluble device works by softly wrapping around nerves to deliver precise, targeted cooling, which numbs nerves and blocks pain signals to the brain. An external pump enables the user to remotely activate the device and then increase or decrease its intensity. After the device is no longer needed, it naturally absorbs into the body bypassing the need for surgical extraction.

The scientists believe the device will be most valuable for patients who undergo routine surgeries or even amputations that commonly require post-operative medications. Surgeons could implant the device during the procedure to help manage the patient’s post-operative pain.

A Northwestern University-led team has developed a small, pain-relieving implant that could provide a much-needed alternative to opioids and other highly addictive medications.

Although opioids are extremely effective, they also are extremely addictive,” said John Rogers, PhD, Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery, who led the device’s development. Jonathan Reeder, former postdoctoral fellow in the Rogers laboratory, is the paper’s first author.

As engineers, we are motivated by the idea of treating pain without drugs — in ways that can be turned on and off instantly, with user control over the intensity of relief,” said Rogers, who is also the founding director of the Querrey Simpson Institute for Bioelectronics.The technology reported here exploits the mechanism that causes your fingers to feel number when cold. Our implant allows that effect to be produced in a programmable way, directly and locally to targeted nerves, even those deep within surrounding soft tissues.

While other cooling therapies and nerve blockers have been tested experimentally, all have limitations that the new device overcomes. Previously, scientists have explored cryotherapies, for example, which are injected with a needle. Instead of targeting specific nerves, these imprecise approaches cool large areas of tissue, potentially leading to unwanted effects such as tissue damage and inflammation.

At its widest point, the tiny device is just five millimeters wide. One end is curled into a cuff that softly wraps around a single nerve, bypassing the need for sutures. By precisely targeting only the affected nerve, the device spares surrounding regions from unnecessary cooling, which could lead to side effects.

You don’t want to inadvertently cool other nerves or the tissues that are unrelated to the nerve transmitting the painful stimuli,” MacEwan said. “We want to block the pain signals, not the nerves that control motor function and enable you to use your hand, for example.”

Source: https://news.feinberg.northwestern.edu/

Ultrasound to Command Bacteria to Nuke Tumors

Scientists at Caltech have genetically engineered, sound-controlled bacteria that seek and destroy cancer cells. In a new paper appearing in the journal Nature Communications, researchers from the lab of Mikhail Shapiro, professor of chemical engineering and Howard Hughes Medical Institute investigator, show how they have developed a specialized strain of the bacteria Escherichia coli (E. coli) that seeks out and infiltrates cancerous tumors when injected into a patient’s body. Once the bacteria have arrived at their destination, they can be triggered to produce anti-cancer drugs with pulses of ultrasound.

The goal of this technology is to take advantage of the ability of engineered probiotics to infiltrate tumors, while using ultrasound to activate them to release potent drugs inside the tumor,” Shapiro says.

The starting point for their work was a strain of E. coli called Nissle 1917, which is approved for medical uses in humans. After being injected into the bloodstream, these bacteria spread throughout the body. The patient’s immune system then destroys them—except for those bacteria that have colonized cancerous tumors, which offer an immunosuppressed environment.

To turn the bacteria into a useful tool for treating cancer, the team engineered them to contain two new sets of genes. One set of genes is for producing nanobodies, which are therapeutic proteins that turn off the signals a tumor uses to prevent an anti-tumor response by the immune system. The presence of these nanobodies allow the immune system to attack the tumor. The other set of genes act like a thermal switch for turning the nanobody genes on when the bacteria reaches a specific temperature.

By inserting the temperature-dependent and nanobody genes, the team was able to create strains of bacteria that only produced the tumor-suppressing nanobodies when warmed to a trigger temperature of 42–43 degrees Celsius. Since normal human body temperature is 37 degrees Celsius, these strains do not begin producing their anti-tumor nanobodies when injected into a person. Instead, they quietly grow inside the tumors until an outside source heats them to their trigger temperature.

But how do you heat bacteria that are located in one specific location, potentially deep inside the body where a tumor is growing? For this, the team used focused ultrasound (FUS). FUS is similar to the ultrasound used for imaging internal organs, or a fetus growing in the womb, but has higher intensity and is focused into a tight point. Focusing the ultrasound on one spot causes the tissue in that location to heat up, but not the tissue surrounding it; by controlling the intensity of the ultrasound, the researchers were able to raise the temperature of that tissue to a specific degree.

Source: https://www.caltech.edu/

Regenerative Therapy Reverses Hearing Loss

The biotechnology company Frequency Therapeutics is seeking to reverse hearing lossnot with hearing aids or implants, but with a new kind of regenerative therapy. The company uses small molecules to program progenitor cells, a descendant of stem cells in the inner ear, to create the tiny hair cells that allow us to hearHair cells die off when exposed to loud noises or drugs including certain chemotherapies and antibiotics. Frequency’s drug candidate is designed to be injected into the ear to regenerate these cells within the cochlea. In clinical trials, the company has already improved people’s hearing as measured by tests of speech perception—the ability to understand speech and recognize words.

Speech perception is the No. 1 goal for improving hearing and the No. 1 need we hear from patients,” says Frequency co-founder and Chief Scientific Officer Chris Loose Ph.D.

In Frequency’s first clinical study, the company saw statistically significant improvements in speech perception in some participants after a single injection, with some responses lasting nearly two years. The company has dosed more than 200 patients to date and has seen clinically meaningful improvements in speech perception in three separate clinical studies, with some improvements lasting nearly two years after a single injection. Another study failed to show improvements in hearing compared to the placebo group, but the company attributes that result to flaws in the design of the trial. Now Frequency is recruiting for a 124-person trial from which preliminary results should be available early next year.

The company’s founders, including Loose, MIT Institute Professor Robert Langer, CEO David Lucchino MBA, Senior Vice President Will McLean Ph.D., and Harvard-MIT Health Sciences and Technology affiliate faculty member Jeff Karp, are already gratified to have been able to help people improve their hearing through the clinical trials. They also believe they’re making important contributions toward solving a problem that impacts more than 40 million people in the U.S. and hundreds of millions more around the world.

Hearing is such an important sense; it connects people to their community and cultivates a sense of identity,” says Karp, who is also a professor of anesthesia at Brigham and Women’s Hospital. “I think the potential to restore hearing will have enormous impact on society.

Source: https://www.frequencytx.com/
AND
https://neurosciencenews.com/

Engineering an “Invisible Cloak” for Bacteria to Deliver Cancer Drugs

Scientists exploring a novel but highly promising avenue of cancer treatment have developed a type of “invisibility cloak” that helps engineered bacteria sneak through the body’s immune defenses. The result is more powerful delivery of anti-cancer drugs and shrinking of tumors in mice, with the scientists hopeful the approach can overcome toxicity issues that have plagued these techniques so far.

Traditional forms of cancer treatment – radiotherapy, chemotherapy and immunotherapy – each have their own strengths when it comes to combating tumors, and what’s known as therapeutic bacteria could bring its own set of skills into the mix. Bacteria itself can have powerful anti-tumor effects, but genetic engineering could allow it to take on entirely new capabilities, including releasing specific compounds or carrying potent anti-cancer drugs. There are a number of challenges in using bacteria for this purpose, however, with the issue of toxicity chief among them. Living bacteria can grow rapidly in the body, and because the body’s immune system sees them as a threat, too many can trigger an extreme inflammatory response.

In clinical trials, these toxicities have been shown to be the critical problem, limiting the amount we can dose bacteria and compromising efficacy,” said Columbia University‘s Jaeseung Hahn, who co-led the research. “Some trials had to be terminated due to severe toxicity.

Addressing this toxicity problem would mean finding (or engineering) bacteria that can evade the body’s immune system and safely make it to a tumor to fulfill their anti-cancer potential. Hahn’s team has made new inroads in this space by turning to sugar polymers called capsular polysaccharides (CAP), which naturally coat bacterial surfaces and protect them from immune attacks.

We hijacked the CAP system of a probiotic E. coli strain Nissle 1917,” said Tetsuhiro Harimoto, the study’s co-lead author. “With CAP, these bacteria can temporarily evade immune attack; without CAP, they lose their encapsulation protection and can be cleared out in the body. So we decided to try to build an effective on/off switch.”

Source: https://www.engineering.columbia.edu/

New Drug Could Protect Against Aging

Senolytics are an emerging class of drugs designed to target zombie-like cells that have stopped dividing and build up in the body as we age, and the past few years have seen some exciting discoveries that demonstrate their potential. Adding another to the list are Mayo Clinic researchers, who have shown that these drugs can protect against aging and its related diseases, by acting on a protein long associated with longevity. The zombie-like cells involved in this research are known as senescent cells, and their accumulation during aging is associated with a range of diseases. Recent studies have shown that using senolytics to clear them out could serve as new and effective treatments for dementia and diabetes, and also improve health and lifespan more broadly.

The Mayo Clinic team were exploring how senolytics can influence levels of a protein called a-klotho, known to help protect older people from the effects of aging. The role of this protein in the aging process is well established and has placed it at the center of much research in this space, with studies demonstrating how it could help reverse osteoarthritis and regenerate old musclesLevels of a-klotho are also known to decrease with age, and studies have shown these declines shorten the lifespan of mice. Conversely, inserting genes that encode for the protein has been shown to increase the lifespan of mice by 30 percent. Boosting its levels in humans has been problematic, however, as its larger size would require it to be administered intravenously. But now the Mayo Clinic scientists believe they have found another route, as senolytic drugs can be administered orally.

They first showed that senescent cells reduce levels of a-klotho in human cells. They then demonstrated that using a combination of senolytic drugs on three different types of mice could counter this and increase levels of a-klotho. This effect was then observed in follow-up experiments on patients with idiopathic pulmonary fibrosis, a lung disease that can cause breathing difficulty, frailty and death.

“We show that there is an avenue for an orally active, small-molecule approach to increase this beneficial protein and also to amplify the action of senolytic drugs,” says James Kirkland, M.D., Ph.D., a Mayo Clinic internist and senior author of the study.

Source: https://www.thelancet.com/

Antibody-Drug Delivery System Kills Cancer Cells With Extreme Precision

It sounds like the stuff of science fiction: a man-made crystal that can be attached to antibodies and then supercharge them with potent drugs or imaging agents that can seek out diseased cells with the highest precision, resulting in fewer adverse effects for the patient.

However, that is precisely what researchers from the Australian Centre for Blood Diseases at Monash University in collaboration with the TU Graz (Austria) have developed: the world’s first metal-organic framework (MOFs) antibody-drug delivery system that has the potential to fast-track potent new therapies for cancer, cardiovascular and autoimmune diseases.

Schematic illustration of the new MOF Antibody crystals and their ability to specifically seek out cancer cells to detect them and deliver highly potent drugs with unprecedented precision

The in vitro study showed that when MOF antibody crystals bind to their target cancer cells and if exposed to the low pH in the cells, they break down, delivering the drugs directly and solely to the desired area.

The metal-organic framework, a mixture of metal (zinc) and carbonate ions, and a small organic molecule (an imidazole, a colourless solid compound that is soluble in water) not only keeps the payload attached to the antibody but can also acts as a reservoir of personalised therapeutics. This is a benefit with the potential to become a new medical tool to target specific diseases with customised drugs and optimised doses.

The findings are now published in the world-leading journal Advanced Materials.

Source: https://www.monash.edu/

How to Program DNA Robots

Scientists have worked out how to best get DNA to communicate with membranes in our body, paving the way for the creation of ‘mini biological computers’ in droplets that have potential uses in biosensing and mRNA vaccinesUNSW’s Dr Matthew Baker and the University of Sydney’s Dr Shelley Wickham co-led the study, published recently in Nucleic Acids Research.

It discovered the best way to design and build DNA ‘nanostructures’ to effectively manipulate synthetic liposomes tiny bubbles which have traditionally been used to deliver drugs for cancer and other diseases. By modifying the shape, porosity and reactivity of liposomes, there are far greater applications, such as building small molecular systems that sense their environment and respond to a signal to release a cargo, such as a drug molecule when it nears its target.

Lead author Dr Matt Baker from UNSW’s School of Biotechnology and Biomolecular Sciences says the study discovered how to buildlittle blocks” out of DNA and worked out how best to label these blocks with cholesterol to get them to stick to lipids, the main constituents of plant and animal cells.

The study discovered the best way to design and build DNA ‘nanostructures’ to effectively manipulate synthetic liposomes (pictured) – tiny bubbles which have traditionally been used to deliver drugs for cancer and other diseases

One major application of our study is biosensing: you could stick some droplets in a person or patient, as it moves through the body it records local environment, processes this and delivers a result so you can ‘read out’ the local environment,” Dr Baker says.

Liposome nanotechnology has shot into prominence with the use of liposomes alongside RNA vaccines such as the Pfizer and Moderna COVID-19 vaccines. “This work shows new ways to corral liposomes into place and then pop them open at just the right time,” Dr Baker says. “What is better is because they are built from the bottom-up out of individual parts we design, we can easily bolt in and out different components to change the way they work.”

Source: https://newsroom.unsw.edu.au/

The Drugmaker Merck Says Its Antiviral Pill Is Effective Against Coronavirus

The drug maker says its pill was shown in a clinical trial to cut the risk of hospitalization or death from the virus in half. Australia is accelerating plans to ease international travel restrictions for its citizens and permanent residents.

The drug maker Merck said on Friday that it would seek authorization for the first antiviral pill for Covid after its drug, known as molnupiravir, was shown in a clinical trial to cut the risk of hospitalization or death in half when given to high-risk people early in their infections.

The treatment could become the first in a wave of antiviral pill products, which experts say could offer a powerful new tool in efforts to tame the pandemic, as they could reach more people than the antibody treatments that are being widely used in the United States for similar patients.

I think it will translate into many thousands of lives being saved worldwide, where there’s less access to monoclonal antibodies, and in this country, too,” said Dr. Robert Shafer, an infectious disease specialist and expert on antiviral therapy at Stanford University.

Late-stage study results of two other antiviral pills, one developed by Pfizer and the other by Atea Pharmaceuticals and Roche, are expected within the next few months.

The Merck drug, which is designed to stop the coronavirus from replicating, is to be taken as four capsules twice a day for five days.

Merck said an independent board of experts monitoring its study data had recommended that its trial be stopped early because the drug’s benefit to patients had proved so convincing. The company said that the Food and Drug Administration had agreed with that decision.

For the research, the monitors looked at data through early August, when the study had enrolled 775 volunteers in the United States and overseas. For volunteers who received the drug, their risk of being hospitalized or dying fell 50 percent, without any concerning side effects, compared with those who received placebo pills, Merck said in a news release announcing the findings.

Seven percent of volunteers in the group that received the drug were hospitalized, and none of them died, compared with a 14 percent rate of hospitalization and death — including eight deaths — in the group that received the placebo.

The Merck pill’s efficacy was lower than that of monoclonal antibody treatments, which mimic antibodies that the immune system generates naturally when fighting the virus. Those drugs have been in high demand recently, but they are expensive, are typically given intravenously, and have proved cumbersome and labor-intensive for hospitals and clinics to administer. Studies have shown that they reduce hospitalizations and deaths 70 to 85 percent in similar high-risk Covid patients.

Source: https://www.nytimes.com/

3 Existing Drugs Fight Coronavirus with ‘almost 100%’ Success

Israeli scientists say they have identified three existing drugs that have good prospects as COVID-19 treatments, reporting that they illustrated high ability to fight the virus in lab tests.

They placed the substances with live SARS‑CoV‑2 and human cells in vitro. The results “showed that the drugs can protect cells from onslaught by the virus with close to 100 percent effectiveness, meaning that almost 100% of the cells lived despite being infected by the virus,” Prof. Isaiah Arkin, the Hebrew University biochemist behind the research, told The Times of Israel.

By contrast, in normal circumstances, around half the cells would have died after two days following contact with the virus.” He added there are strong indications that the drugs will be robust against changing variants.

Arkin, part of a Hebrew University center that specializes in repurposing existing drugs, said that he screened more than 3,000 medicines for suitability, in what he describes as a needle-in-a-haystack search. This approach can provide a fast track to find treatments as the drugs have already been tried and tested, and he hopes to work with a pharmaceutical company to quickly get the medicines he identified clinically tested for COVID-19.

We have the vaccine, but we shouldn’t rest on our laurels, and I would like to see these drugs become part of the arsenal that we use to fight the coronavirus,” he said. When confronting SARS‑CoV‑2, the drugs in question — darapladib, which currently treats atherosclerosis; the cancer drug Flumatinib; and an HIV medicine — don’t target the spike protein. Rather, they target one of two other proteins: the envelope protein and the 3a protein. These proteins — especially the envelope proteinhardly change between variants, and even between diseases from the coronavirus family. As such, drugs that target them are likely to remain effective in spite of mutations, Arkin said.

Source: https://www.timesofisrael.com/