Sticker on the Skin Provides Clear Image of Heart, Lungs

Ultrasound imaging is a safe and noninvasive window into the body’s workings, providing clinicians with live images of a patient’s internal organs. To capture these images, trained technicians manipulate ultrasound wands and probes to direct sound waves into the body. These waves reflect back out to produce high-resolution images of a patient’s heart, lungs, and other deep organs.

Currently, ultrasound imaging requires bulky and specialized equipment available only in hospitals and doctor’s offices. But a new design by MIT engineers might make the technology as wearable and accessible as buying Band-Aids at the pharmacy. In a paper appearing today in Science, the engineers present the design for a new ultrasound sticker — a stamp-sized device that sticks to skin and can provide continuous ultrasound imaging of internal organs for 48 hours.

The researchers applied the stickers to volunteers and showed the devices produced live, high-resolution images of major blood vessels and deeper organs such as the heart, lungs, and stomach. The stickers maintained a strong adhesion and captured changes in underlying organs as volunteers performed various activities, including sitting, standing, jogging, and biking. The current design requires connecting the stickers to instruments that translate the reflected sound waves into images. The researchers point out that even in their current form, the stickers could have immediate applications: For instance, the devices could be applied to patients in the hospital, similar to heart-monitoring EKG stickers, and could continuously image internal organs without requiring a technician to hold a probe in place for long periods of time.

If the devices can be made to operate wirelessly — a goal the team is currently working toward — the ultrasound stickers could be made into wearable imaging products that patients could take home from a doctor’s office or even buy at a pharmacy.

We envision a few patches adhered to different locations on the body, and the patches would communicate with your cellphone, where AI algorithms would analyze the images on demand,” says the study’s senior author, Xuanhe Zhao, professor of mechanical engineering and civil at MIT. “We believe we’ve opened a new era of wearable imaging: With a few patches on your body, you could see your internal organs.

The study also includes lead authors Chonghe Wang and Xiaoyu Chen, and co-authors Liu Wang, Mitsutoshi Makihata, and Tao Zhao at MIT, along with Hsiao-Chuan Liu of the Mayo Clinic in Rochester, Minnesota.


Saudi Arabia to Spend $1 billion a Year to Slow Aging

Anyone who has more money than they know what to do with eventually tries to cure aging. Google founder Larry Page has tried it. Jeff Bezos has tried it. Tech billionaires Larry Ellison and Peter Thiel have tried it. Now the kingdom of Saudi Arabia, which has about as much money as all of them put together, is going to try it. The Saudi royal family has started a not-for-profit organization called the Hevolution Foundation that plans to spend up to $1 billion a year of its oil wealth supporting basic research on the biology of aging and finding ways to extend the number of years people live in good health, a concept known as “health span.”

The sum, if the Saudis can spend it, could make the Gulf state the largest single sponsor of researchers attempting to understand the underlying causes of aging—and how it might be slowed down with drugs. The foundation hasn’t yet made a formal announcement, but the scope of its effort has been outlined at scientific meetings and is the subject of excited chatter among aging researchers, who hope it will underwrite large human studies of potential anti-aging drugs. The fund is managed by Mehmood Khan, a former Mayo Clinic endocrinologist and the onetime chief scientist at PespsiCo, who was recruited to the CEO job in 2020. ““Our primary goal is to extend the period of healthy lifespan,” Khan said in an interview. “There is not a bigger medical problem on the planet than this one.

The idea, popular among some longevity scientists, is that if you can slow the body’s aging process, you can delay the onset of multiple diseases and extend the healthy years people are able to enjoy as they grow older. Khan says the fund is going to give grants for basic scientific research on what causes aging, just as others have done, but it also plans to go a step further by supporting drug studies, including trials of “treatments that are patent expired or never got commercialized.”

We need to translate that biology to progress towards human clinical research. Ultimately, it won’t make a difference until something appears in the market that actually benefits patients,” Khan says.

Khan says the fund is authorized to spend up to $1 billion per year indefinitely, and will be able to take financial stakes in biotech companies. By comparison, the division of the US National Institute on Aging that supports basic research on the biology of aging spends about $325 million a year.

Hevolution hasn’t announced what projects it will back, but people familiar with the group say it looked at funding a $100 million X Prize for age reversal technology and has reached a preliminary agreement to fund a test of the diabetes drug metformin in several thousand elderly people.

That trial, known as “TAME” (for “Targeting Aging with Metformin”), has been touted as the first major test of any drug to postpone aging in humans, but the study has languished for years without anyone willing to pay for it.


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.


Glue Seals Bleeding Organs in Seconds

Inspired by the sticky substance that barnacles use to cling to rocks, MIT engineers have designed a strong, biocompatible glue that can seal injured tissues and stop bleeding. The new paste can adhere to surfaces even when they are covered with blood, and can form a tight seal within about 15 seconds of application. Such a glue could offer a much more effective way to treat traumatic injuries and to help control bleeding during surgery, the researchers say.

We are solving an adhesion problem in a challenging environment, which is this wet, dynamic environment of human tissues. At the same time, we are trying to translate this fundamental knowledge into real products that can save lives,” says Xuanhe Zhao, a professor of mechanical engineering and civil and environmental engineering at MIT and one of the senior authors of the study. Finding ways to stop bleeding is a longstanding problem that has not been adequately solved, Zhao says. Sutures are commonly used to seal wounds, but putting stitches in place is a time-consuming process that usually isn’t possible for first responders to perform during an emergency situation. Among members of the military, blood loss is the leading cause of death following a traumatic injury, and among the general population, it is the second leading cause of death following a traumatic injury.

In recent years, some materials that can halt bleeding, also called hemostatic agents, have become commercially available. Many of these consist of patches that contain clotting factors, which help blood to clot on its own. However, these require several minutes to form a seal and don’t always work on wounds that are bleeding profusely. Zhao’s lab has been working to address this problem for several years

For their new tissue glue, the researchers once again drew inspiration from the natural world. This time, they focused their attention on the barnacle, a small crustacean that attaches itself to rocks, ship hulls, and even other animals such as whales. These surfaces are wet and often dirty — conditions that make adhesion difficult. “This caught our eye,” Yuk says. “It’s very interesting because to seal bleeding tissues, you have to fight with not only wetness but also the contamination from this outcoming blood. We found that this creature living in a marine environment is doing exactly the same thing that we have to do to deal with complicated bleeding issues.” The researchers’ analysis of barnacle glue revealed that it has a unique composition. The sticky protein molecules that help barnacles attach to surfaces are suspended in an oil that repels water and any contaminants found on the surface, allowing the adhesive proteins to attach firmly to the surface.

The MIT team decided to try to mimic this glue by adapting an adhesive they had previously developed. This sticky material consists of a polymer called poly(acrylic acid) embedded with an organic compound called an NHS ester, which provides adhesion, and chitosan, a sugar that strengthens the material. The researchers froze sheets of this material, ground it into microparticles, and then suspended those particles in medical grade silicone oil.

Christoph Nabzdyk, a cardiac anesthesiologist and critical care physician at the Mayo Clinic in Rochester, Minnesota, is also a senior author of the paper, which appears today in Nature Biomedical Engineering. MIT Research Scientist Hyunwoo Yuk and postdoc Jingjing Wu are the lead authors of the study.


Early Cancer Detection Test

Mayo Clinic today recognized the debut of a groundbreaking multi-cancer early detection (MCED) test called Galleri™ that can detect more than 50 types of cancers through a simple blood draw. The  Galleri test is intended  to complement U.S. guideline-recommended cancer screenings.

Mayo Clinic Oncologist Minetta Liu, M.D. was involved in the development of the new test. “Today, many cancers are found too late, leading to poor outcomes,” says Dr. Liu. “The ability to detect cancer early is critical to successful treatment.”

Cancer is expected to become the leading cause of death in the U.S. this year. Currently recommended cancer screening tests only cover five cancer types and screen for a single cancer at a time. In fact, there are no recommended early detection screening tests for other cancers, which account for 71% of cancer deaths.

Researchers used the Galleri test in the Circulating Cell-free Genome Atlas (CCGA) Study, a prospective, observational, longitudinal study designed to characterize the landscape of genomic cancer signals in the blood of people with and without cancer. In the study, the Galleri test demonstrated the ability to detect more than 50 types of cancers — over 45 of which have no recommended screening tests today — with a low false-positive rate of less than 1%.

According to Dr. Liu, when a cancer signal is detected, the Galleri test can identify where in the body the cancer is located with high accuracy — a critical component to help enable health care providers to direct diagnostic next steps and care.

We are grateful to Mayo Clinic for its dedication to advancing new technologies for early cancer detection and for playing a pivotal role in the development of Galleri,” says Dr. Josh Ofman, chief medical officer and head of external affairs at GRAIL.“A simple blood test capable of detecting more than 50 cancers is a ground-breaking advancement and could have a tremendous human and economic benefit.

Initial results from the interventional PATHFINDER Study, which involved the return of Galleri test results to providers to communicate to participants, were presented today at the 2021 American Society of Clinical Oncology Annual Meeting. They demonstrate Galleri’s performance in the clinical setting was consistent with findings from previous observational studies, underscoring the potential real-world ability of Galleri to find deadly cancers earlier.


Can Plasma From Recovered Covid-19 Patients Cure Infected Others?

US Food and Drug Administration (FDA) officials announced today they have approved plans for nationwide trials of two treatments for Covid-19, the global pandemic disease caused by the new coronavirus—and for their simultaneous use in perhaps hundreds of hospitals.

The therapeutic agents—convalescent plasma and hyperimmune globulin—are both derived from the blood of people who have recovered from the disease, decoctions of the antibodies that the human immune system makes to fight off germs.


This is an important area of research—the use of products made from a recovered patient’s blood to potentially treat Covid-19,” said FDA commissioner Stephen Hahn in a release announcing the trials. “The FDA had played a key role in organizing a partnership between industry, academic institutions, and government agencies to facilitate expanded access to convalescent plasma. This is certainly a great example of how we can all come together to take swift action to help the American people during a crisis.”

Physicians are already using a somewhat haphazard collection of antiviral and other drugs for people critically ill with Covid-19, because they don’t have any other options. Nothing—no drug, no vaccine—is approved for use specifically against Covid-19 in the United States, so any new possibility is a hopeful one. Convalescent plasma and hyperimmune globulin join the rarified group of therapeutics that scientists are testing, including a trial of the Ebola drug remdesivir and the much-hyped antimalarial/immune suppressants chloroquine and hydroxychloroquine.

Using blood products from people who’ve already beaten a disease is a century-old approach, predating vaccines and antibiotics. Inspired by its use against polio, two physicians at a Naval hospital in Massachusetts tried it on people who had pneumonia as a result of influenza in 1918, with enough success to warrant more tests. The quality of actual studies of efficacy has varied over the decades, but health care workers used convalescent plasma against SARS, MERS, and Ebola. And a couple of studies—small and preliminary—have shown convalescent plasma having some promise against SARS-CoV-2 as well.

It was all promising enough that the FDA wanted to make sure current patients could have access to the plasma at the same time that researchers were starting a more rigorous investigation. “This seems like ancient history, but maybe it isn’t. There have been niche uses of it for a while,” says Michael Joyner, a physiologist at the Mayo Clinic who in March spearheaded the creation of an ad hoc coalition of researchers interested in pursuing the therapy. Joyner is facilitating the 40-center trial of the new therapies approved today by the FDA, with researchers at Johns Hopkins leading the science. (Joyner himself received gamma globulin, a variant of the treatment, as a preventative against hepatitis B in the 1980s, when he was a medical student.)

At Houston Methodist Hospital, James Musser, the chair of Pathology and Genome Medicine, is a friend of Arturo Casadevall, the Johns Hopkins University immunologist who proposed using convalescent serum early in the pandemic. Musser pushed to get his hospital involved, putting out a call for donors—people who had confirmed positive tests for the virus and had gone at least 14 days without symptoms. His hospital is already doing compassionate-use transfusions. “So far, as of yesterday, we’ve transfused four patients,” Musser said on Thursday. He expected a fifth to receive plasma today. And how’d it work?The truth is, it’s far too early,” Musser says. “We, nationally, need to do controlled trials and understand, first and foremost, is this a safe therapeutic? There’s lots of reasons to think it will be, but you never know.”


DNA Nanorobots Target Breast Cancer Cells

According to the Mayo Clinic, about 20% of breast cancers make abnormally high levels of a protein called human epidermal growth factor receptor 2 (HER2). When displayed on the surface of cancer cells, this signaling protein helps them proliferate uncontrollably and is linked with a poor prognosis. Now, researchers have developed a DNA nanorobot that recognizes HER2 on breast cancer cells, targeting them for destruction.

Current therapies for HER2-positive breast cancer include monoclonal antibodies, such as trastuzumab, that bind to HER2 on cells and direct it to the lysosome — an organelle that degrades biomolecules. Lowering the levels of HER2 slows cancer cell proliferation and triggers cell death. Although monoclonal antibodies can lead to the death of cancer cells, they have severe side effects and are difficult and expensive to produce. In a previous study, Yunfeng Lin and colleagues identified a short sequence of DNA, called an aptamer, that recognizes and binds HER2, targeting it for lysosomal degradation in much the same way that monoclonal antibodies do. But the aptamer wasn’t very stable in serum. So the researchers wanted to see if adding a DNA nanostructure, called a tetrahedral framework nucleic acid (tFNA), could increase the aptamer‘s biostability and anti-cancer activity.


To find out, the team designed DNA nanorobots consisting of the tFNA with an attached HER2 aptamer. When injected into mice, the nanorobots persisted in the bloodstream more than twice as long as the free aptamer. Next, the researchers added nanorobots to three breast cancer cell lines in petri dishes, showing that they killed only the HER2-positive cell line. The addition of the tFNA allowed more of the aptamer to bind to HER2 than without tFNA, leading to reduced HER2 levels on cell surfaces. Although the nanorobot is much easier and less expensive to make than monoclonal antibodies, it likely needs further improvement before it could be used to treat breast cancer in the clinic, the researchers say.

The findings are published  in the ACS journal Nano Letters.