Articles from April 2023

High-Tech Earbud Detects Alzheimer’s Far Earlier

It is believed that long before Alzheimer’s or Parkinson’s diseases present more obvious symptoms, the disorders may be noticeable in subtle changes to a person’s sleep patterns. A new project aims to see if such telltale changes could be detected by a small earbud-like device, allowing action to be taken much sooner. The four-year PANDA (Progression Assessment in Neurodegenerative Disorders of Aging) project is a collaboration between Denmark’s Aarhus University, Rigshospitalet University, and health tech company T&W Engineering. It’s centered around an experimental device known as the ear-EEG (electroencephalogram). Although the Aarhus-designed wearable looks much like a standard earbud, it actually monitors electrical activity in the brain by measuring minuscule voltage changes on the surface of the skin within the ear canal. It’s also equipped with an oximeter for measuring blood oxygen levels, a thermometer for measuring body temperature, and a microphone for monitoring heart rate and respiration.

Unlike existing sleep-monitoring systems, which typically require people to sleep a few nights in a clinic while hard-wired to numerous electrodes, the ear-EEG could be used over longer periods in people’s own homes. Additionally, because it’s much less obstructive than traditional setups, it should give a better indication of its wearer’s natural, normal sleep patterns. Plans call for the device to be tested on groups of volunteers both with and without Alzheimer’s and Parkinson’s, to see if consistently detectable patterns emerge in the sleep patterns of those groups. Should the study be successful, it is hoped that people who are at risk of the diseases could eventually use an ear-EEG to monitor their sleep patterns for several days or weeks on an annual basis.

Alzheimer’s and Parkinson’s are diseases that creep up over many years,” said Aarhus University‘s Prof. Preben Kidmose. “Diagnosis is generally so late that the only treatment option is to treat the symptoms. In the project, we’re going to try to identify signs of the two diseases 10 to 15 years before the first problems begin to occur, and if we can, far better treatment options will be possible.”


New Gene Therapy Could Stop Parkinson’s

In almost 70 years, our understanding of how Parkinson’s disease wreaks havoc on the nervous system has grown tremendously. Advances in genetic sequencing, for instance, have revealed that up to 15 percent of all cases of Parkinson’s can be attributed to inherited mutations in a person’s DNA. But large gaps in our understanding remain, including what causes the majority of cases and how to definitively test for the disease. Most astonishingly, today’s gold standard treatment for Parkinson’slevodopa medications—was discovered 68 years ago. Levodopa is effective at reducing Parkinson’s hallmark symptoms like tremors, slowness, and stiffness. The underlying theory is that Parkinson’s patients lose cells that make dopamine, and levodopa acts as a substitute.

Crucially, however, levodopa cannot stop or slow the progression of the neurodegenerative disease—merely provide some respite to the symptoms. Many researchers hope to find a more permanent cure by targeting the source and directly fixing mistakes in patients’ genes that lead to Parkinson’s in the first place. In a new study published April 19 in the journal Science Advances, one group reports having acquired the ability to overcome a (literal) barrier holding genetic intervention back.

New ways to treat Parkinson’s disease can’t come fast enough. More than 8.5 million people worldwide have the disease, and it’s the fastest-growing neurological cause of disability and death. Not only can these new findings introduce a new generation of Parkinson’s treatments, it could fundamentally change the way we treat diseases of the brain.

Our ultimate goal is to treat neurological diseases, such as Parkinson’s, early and non-invasively,” José Obeso, a neurologist at the Abarca Campal Integral Neuroscience Center in Spain and the senior author of the new research, told Spanish newspaper El País. “If all goes well, we could start testing on patients in the summer of 2024.”

Though the roots of Parkinson’s disease remain mysterious, researchers have figured out that dopamine is central to the puzzle. You may know this chemical as a pleasure hormone, but more generally it’s a key component of neurons’ messaging system. A structure in humans’ midbrain called the substantia nigra controls movement and coordination through cells that release dopamine. But in Parkinson’s patients, 80 percent or more of these cells are killed off.


A Simple Test Diagnoses Early Cancer

MIT engineers have designed a new nanoparticle sensor that could enable early diagnosis of cancer with a simple urine test. The sensors, which can detect many different cancerous proteins, could also be used to distinguish the type of a tumor or how it is responding to treatment. The new diagnostic, which is based on analysis of urine samples, could also be designed to reveal whether a tumor has metastasized. The nanoparticles are designed so that when they encounter a tumor, they shed short sequences of DNA that are excreted in the urine. Analyzing these DNAbarcodes” can reveal distinguishing features of a particular patient’s tumor. The researchers designed their test so that it can be performed using a strip of paper, similar to an at-home Covid test, which they hope could make it affordable and accessible to as many patients as possible.

We are trying to innovate in a context of making technology available to low- and middle-resource settings. Putting this diagnostic on paper is part of our goal of democratizing diagnostics and creating inexpensive technologies that can give you a fast answer at the point of care,” says Sangeeta Bhatia, Professor of Health Sciences at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

In tests in mice, the researchers showed that they could use the sensors to detect the activity of five different enzymes that are expressed in tumors. They also showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample, using a microfluidic device to analyze the samples.

Bhatia is the senior author of the paper, which appears today in Nature Nanotechnology. Liangliang Hao, a former MIT research scientist who is now an assistant professor of biomedical engineering at Boston University, is the lead author of the study.


New Gel Stops Brain Tumors

Medication delivered by a novel gel cured 100% of mice with an aggressive brain cancer, a striking result that offers new hope for patients diagnosed with glioblastoma, one of the deadliest and most common brain tumors in humans.

Despite recent technological advancements, there is a dire need for new treatment strategies,” said Honggang Cui, a Johns Hopkins University chemical and biomolecular engineer who led the research. “We think this hydrogel will be the future and will supplement current treatments for brain cancer.”

Cui’s team combined an anticancer drug and an antibody in a solution that self-assembles into a gel to fill the tiny grooves left after a brain tumor is surgically removed. The gel can reach areas that surgery might miss and current drugs struggle to reach to kill lingering cancer cells and suppress tumor growth.

The gel also seems to trigger an immune response that a mouse’s body struggles to activate on its own when fighting glioblastoma. When the researchers rechallenged surviving mice with a new glioblastoma tumor, their immune systems alone beat the cancer without additional medication. The gel appears to not only fend off cancer but help rewire the immune system to discourage recurrence with immunological memory, researchers said.

Still, surgery is essential for this approach, the researchers said. Applying the gel directly in the brain without surgical removal of the tumor resulted in a 50% survival rate.

The surgery likely alleviates some of that pressure and allows more time for the gel to activate the immune system to fight the cancer cells,” Cui said.

The gel solution consists of nano-sized filaments made with paclitaxel, an FDA-approved drug for breast, lung, and other cancers. The filaments provide a vehicle to deliver an antibody called aCD47. By blanketing the tumor cavity evenly, the gel releases medication steadily over several weeks, and its active ingredients remain close to the injection site.

The results are published in Proceedings of the National Academy of Sciences.


How a Microwave-Sized Device Could Heal a Third of Myelomas

Under CEO Paul Stoffels, Belgian biotech Galapagos is testing a device that manufactures CAR-T cancer therapies in hospitals, bringing down the wait time and price. When it works, CAR-T cancer therapy can appear miraculous. With a single infusion of their own immune T-cellsgenetically modified to find and kill cancer in the blood—about half of patients with leukemia and lymphoma, and about a third with myeloma, have a complete remission, achieving a functional “cure.” For the most prevalent type of pediatric cancer, acute lymphoblastic leukemia, CAR-T therapy has demonstrated complete remission rates as high as 90%. The first two patients treated with CAR-T therapy, in 2010—adult men who had end-stage chronic lymphocytic leukemia—were still in remission a decade later. The U.S. Food and Drug Administration has approved a total of six CAR-T therapies since 2017, all for the treatment of blood cancers.

A 2022 survey by Mayo Clinic researchers found that the median time on the waiting list for CAR-T therapy was six months, and that only a quarter of patients eventually received it.

Unlike regular drugs, so-called autologous CAR-T infusions are “living medicines,” custom-made for each patient. Typically, patients will get blood drawn in a hospital or special center. The T cells are separated out, and shipped refrigerated or frozen to a central biomanufacturing facility where they’re genetically  “reprogrammed” to express a tumor-seeking molecule, called a chimeric antigen receptor, or CAR, on their surface. The modified cells are “expanded” in an incubator for a few days or weeks to boost their numbers enough to create a therapeutic dose. After several quality testing steps, the modified CAR-T cells are frozen and sent back to the hospital to deliver to the patient. The process typically takes at least two weeks and up to eight weeks, “vein to vein.”

Current CAR-T treatments have list prices in the high $300,000 to high $400,000 range. “The reason it’s so costly,” explains Travis Young, VP of Biologics at the nonprofit California Institute for Biomedical Research (Calibr), “is because every point in that manufacturing process has to be very highly controlled. It requires a technician that has a lot of training, it requires clean rooms, it requires the infrastructure for shipping and cryopreservation, and then the biggest time is the pre-release testing to ensure the sterility and potency of the product.” There are numerous opportunities for glitches. “The supply chain is in its infancy,” Young says. “And it’s not just the infrastructure, it’s the number of people that have the training to do this.”

Companies are hacking away at these challenges in different ways, aiming to reduce the complexity, time, and ultimately cost of delivering CAR-T treatments to more patients. One of the more unlikely contenders is Belgium-based Galapagos NV, which last June announced a bold plan to manufacture these expensive therapies more quickly and affordably, by developing them not in a centralized facility, but at the point of care, using a small, highly automated device the size of a home microwave.


Tiny biobattery Runs on Bacteria

Last fall, Professor Seokheun “Sean” Choi from the Watson College (Binghamton University) and his Bioelectronics and Microsystems Laboratory published their research into an ingestible biobattery activated by the Ph factor of the human intestine. Now, he and PhD student Maryam Rezaie have taken what they learned and incorporated it into new ideas for use outside the body. A new study in the journal Small, which covers nanotechnology, shares the results from using spore-forming bacteria similar to the previous ingestible version to create a device that potentially would still work after 100 years.

The overall objective is to develop a microbial fuel cell that can be stored for a relatively long period without degradation of biocatalytic activity and also can be rapidly activated by absorbing moisture from the air,” said Choi, a faculty member in the Department of Electrical and Computer Engineering at the Thomas J. Watson College of Engineering and Applied Science.

We wanted to make these biobatteries for portable, storable and on-demand power generation capabilities,” Choi said. “The problem is, how can we provide the long-term storage of bacteria until used? And if that is possible, then how would you provide on-demand battery activation for rapid and easy power generation? And how would you improve the power?

The dime-sized fuel cell was sealed with a piece of Kapton tape, a material that can withstand temperatures from -500 to 750 degrees Fahrenheit. When the tape was removed and moisture allowed in, the bacteria mixed with a chemical germinant that encouraged the microbes to produce spores. The energy from that reaction produced enough to power an LED, a digital thermometer or a small clock.

Heat activation of the bacterial spores cut the time to full power from 1 hour to 20 minutes, and increasing the humidity led to higher electrical output. After a week of storage at room temperature, there was only a 2% drop in power generation.


Cutting-Edge Advances In Cancer treatment That Could Change Lives

What if radiation treatments could be given in a handful of seconds rather than weeks of treatments? If surgeons could actually see tumor cells rather than simply hoping they got rid of them all? If scientists could come up with new ways to detect, treat and understand tumors? These were among some of the ideas presented this week in Orlando at the American Association for Cancer Research annual conference, where more than 6,500 scientists shared their work and their hopes for improving the lives of cancer patients. Work against cancer has continued over the last three years, despite the pandemic, said Dr. Robert Vonderheide, the conference’s program committee chair. The thousands of presentations and 20,000-person turnout should convince people of that. Obviously, lots of the research is worth public attention. But with Vonderheide’s guidance, USA TODAY picked three ideas that seemed among the most surprising and hopeful, the kinds of approaches that have the potential to transform cancer treatment and patients’ lives.

The first is “flashradiation, which concentrates weeks of treatments into a few days; the second, an imaging technology that lights up cancer cells to help surgeons track them down.

Two of the most fundamental tools, cancer surgery and cancer radiation, are undergoing before our eyes fundamental changes in their technology,” said Vonderheide, who directs the Abramson Cancer Center at the University of Pennsylvania. “They are each promising better success.” A third line of research is providing insights into the role of the nervous system in cancer, which could eventually be used to help patients sleep better, heal faster and live longer. Researchers typically focus on a tumor, but there are “systemic signals that might tell us how best to treat a patient or that a patient actually has a lurking cancer,” Vonderheide said. Like the immune system, which has increasingly been manipulated to help fight cancer over the last decade, the nervous system monitors the body and remembers what it encounters.

The immune system is probably the first system to know that cancer exists. And probably the nervous system is the next one,” he said. “Maybe there’s new inroads in early detection if we focus on neurological health and immune health.” None of these new approaches is readily available yet, but Vonderheide thinks they’re among the advances worth watching.

At least half of patients with solid tumors endure radiation at some point during their treatment. Radiation typically takes about 15 minutes, though sessions can last an hour or more and are scheduled every weekday for three to nine weeks – requiring a total of 15 to 40 visits. Patients may suffer skin burns, dry mouth, difficulties eating and swallowing, and exhaustion. They must upend their lives and often a loved one’s to get to a clinic so many times.

Radiation therapy is traditionally delivered in small doses over weeks so it can efficiently kills tumor cells while being less toxic to surrounding healthy tissue, said Constantinos Koumenis, a professor of radiation biology at the University of Pennsylvania‘s Perelman School of Medicine. But as many radiation patients can attest, treatments still do plenty of damage to normal tissue. Instead, Koumenis and dozens of other research teams have been testing “flash radiation,” which uses ultra high dose rate beams of energy to zap tumor cells. Patients might get the same amount of radiation in just two to four sessions of less than 1 second each. “The vulnerability of the tumor cells is essentially the same,” Koumenis said. “What’s different is the normal tissue is more resistant to the flash radiation.”


Edible Battery Made Of Almonds For Use In Ingestible Medical Devices

Researchers at the Italian Institute of Technology in Milan have developed the rechargeable prototype out of common-place food stuffs with the hopes of revolutionising ingestible medical devices.

The core of the device is represented by a couple of electrodes… To have it working we are using two materials, two molecules. For the anode, we are using riboflavin which is a vitamin we can find in almonds… and for the Cathode we are using quercetin. It’s sold as a food supplement and can be found in capers,” explained Mario Caironi, the coordinator of the project. Ingestible devices like biosensors, cameras, and drug delivery systems already exist but typically cannot be digested by the human body. Therefore, if complications arise during the digestion process, surgical intervention can be required to remove the device. The advantage of this gadget made from almonds, capers, activated charcoal, seaweed, gold leaf and beeswax, is that it can be digested completely without any health risks.

Other potential applications aside from health devices could include food quality monitoring  edible soft robotics. The battery prototype operates at 0.65 volts, which is too low to cause problems inside the human body. It provides a current of 48 microamps for up to 12 minutes and can power a small LED or other miniature electronic devices. The team is now working to boost capacity as well as shrink the device into a pill-sized container that would be easier to swallow.

The proof-of-concept battery cell was described recently in a paper published in the journal Advanced Materials.


Reversing Age To Treat Alzheimer’s, Cancer and Cardiac Risks

RNA sequencing and gene network data are used to identify candidate genes that could turn back the “transcriptome clock” that reflects the biological age of distinct human cell types.

Technology has the potential to treat major age-related diseases including cardiovascular disease, cardiovascular disease, and cancer. More than 150,000 people die each day across the globe, about two-thirds of them from age-related causes like cancer, neurodegenerative diseases, strokes, and cardiovascular disease. If the process of aging could be slowed or reversed, the incidence of these conditions would be dramatically reduced, and more humans would live longer, healthier lives. However, aging is a complex process involving multiple biological systems – there is no single biomarker for aging. Therefore, developing treatments that target the root causes of aging is very challenging. Ichor is a Validation Project at the Wyss Institute of Harvard that aims to address this problem using high-throughput genetic screening to identify networks of genes that are strongly implicated in aging processes and develop RNA-based therapies that can make old cells young again.

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How to Reverse Alzheimer’s

MIT neuroscientists have found a way to reverse neurodegeneration and other symptoms of Alzheimer’s disease by interfering with an enzyme that is typically overactive in the brains of Alzheimer’s patients. When the researchers treated mice with a peptide that blocks the hyperactive version of an enzyme called CDK5, they found dramatic reductions in neurodegeneration and DNA damage in the brain. These mice also showed improvements in their ability to perform tasks such as learning to navigate a water maze.

We found that the effect of this peptide is just remarkable,” says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the senior author of the study. “We saw wonderful effects in terms of reducing neurodegeneration and neuroinflammatory responses, and even rescuing behavior deficits.

With further testing, the researchers hope that the peptide could eventually be used as a treatment for patients with Alzheimer’s disease and other forms of dementia that have CDK5 overactivation. The peptide does not interfere with CDK1, an essential enzyme that is structurally similar to CDK5, and it is similar in size to other peptide drugs that are used in clinical applicationsPicower Institute Research Scientist Ping-Chieh Pao is the lead author of the paper, which appears this week in the Proceedings of the National Academy of Sciences. Tsai has been studying CDK5’s role in Alzheimer’s disease and other neurodegenerative diseases since early in her career. As a postdoc, she identified and cloned the CDK5 gene, which encodes a type of enzyme known as a cyclin-dependent kinase. Most of the other cyclin-dependent kinases are involved in controlling cell division, but CDK5 is not. Instead, it plays important roles in the development of the central nervous system, and also helps to regulate synaptic function.