Reprogramming Aging Bodies Back to Youth

A little over 15 years ago, scientists at Kyoto University in Japan made a remarkable discovery. When they added just four proteins to a skin cell and waited about two weeks, some of the cells underwent an unexpected and astounding transformation: they became young again. They turned into stem cells almost identical to the kind found in a days-old embryo, just beginning life’s journey.
At least in a petri dish, researchers using the procedure can take withered skin cells from a 101-year-old and rewind them so they act as if they’d never aged at all.

You must be logged in to view this content.

Anti-inflammatory Molecules Decline in the Aging Brain

Aging involves complicated plot twists and a large cast of characters: inflammation, stress, metabolism changes, and many others.

Now, a team of Salk Institute and UC San Diego scientists reveal another factor implicated in the aging process—a class of lipids called SGDGs (3-sulfogalactosyl diacylglycerols) that decline in the brain with age and may have anti-inflammatory effects.

 

The research, published in Nature Chemical Biology, helps unravel the molecular basis of brain aging, reveals new mechanisms underlying age-related neurological diseases, and offers future opportunities for therapeutic intervention.

You must be logged in to view this content.

Personalized Skin Cancer Vaccine

Two major pharmaceutical companies are testing a personalized vaccine that might prevent the recurrence of a specific type of skin cancer. Moderna, one of the companies behind the COVID-19 vaccine, and Merck, an enterprise focused largely on oncology and preventative medicines, are teaming up to see if they can reduce the public’s risk of re-developing the deadliest form of skin cancer: melanoma.

The vaccine essentially combines two medical technologies: the mRNA vaccine and Merck’s Keytruda. As with the COVID-19 vaccine, mRNA shots don’t require an actual virus. Instead, they use a disease’s genetic code to “teach” the immune system to recognize and fight that particular illness. This makes it relatively easy and inexpensive for scientists to develop mRNA vaccines and edit them if a new form of the disease emerges. Keytruda, meanwhile, is a prescription medication that helps prevent melanoma from coming back after known cancer cells have been surgically removed.

Moderna and Merck are testing the feasibility of not only creating a two-in-one drug with both technologies but also customizing individual vaccines to suit their respective patients. Each vaccine is engineered to activate the patient’s immune system, which in turn deploys T cells (a type of white blood cell known to fight cancer) that go after the specific mutations of a patient’s tumor. Keytruda assists this effort by barring certain cell proteins from getting in the way of T cells’ intervention.

The experimental drug is currently in its second clinical trial out of three. The trial involves 157 participants with high-risk melanoma who just successfully underwent surgical removal. Some of the participants were given the personalized vaccine, while others were given Keytruda alone. Moderna and Merck will observe whether the participants’ melanoma returns over the span of approximately one year, with primary data expected at the end of this year.

If a vaccine preventing the recurrence of melanoma does in fact become commercially available, it could prevent more than 7,000 deaths per year in the US alone.

Source: https://www.extremetech.com/

Human Brain Cells Transplanted into Baby Rats’ Brains

Human neurons transplanted into a rat’s brain continue to grow, forming connections with the animals’ own brain cells and helping guide their behavior, new research has shown. In a study published in the journal Nature today, lab-grown clumps of human brain cells were transplanted into the brains of newborn rats. They grew and integrated with the rodents’ own neural circuits, eventually making up around one-sixth of their brains. These animals could be used to learn more about human neuropsychiatric disorders, say the researchers behind the work.

It’s an important step forward in progress into [understanding and treating] brain diseases,” says Julian Savulescu, a bioethicist at the National University of Singapore, who was not involved in the study. But the development also raises ethical questions, he says, particularly surrounding what it means to “humanizeanimals.

Sergiu Pașca at the University of Stanford has been working for more than a decade with neural organoids—small clumps of neurons, grown in a dish, that resemble specific brain regions. These organoids are often created from human skin cells, which are first made into stem cells. The stem cells can then be encouraged to form neurons in the lab, under the right conditions. The resulting organoids can be used to study how brain cells fire and communicate—and how they malfunction in some disorders.

But there’s only so much a clump of cells in the lab can tell you. When it comes down to it, these cells don’t really replicate what is happening in our brains—which is why Pașca and many others in the field avoid the commonly used term “mini-brains. The organoid cells can’t form the same complex connections. They don’t fire in the same way, either. And they aren’t as big as the cells in our brains. “Even when we kept human neurons for hundreds of days … we noticed that human neurons don’t grow to the size to which a human neuron in a human brain would grow,” says Pașca.

It is also impossible to tell how changes to neurons in the lab might lead to symptoms of a neuropsychiatric disorder. If cells in a dish show a change in their shape, the way they fire, or the proteins they make, what does that mean for a person’s memory or behavior, for example? To get around these issues, Pașca and his colleagues transplanted organoids into the brains of living rats—specifically, newborn rats. The brains of very young animals undergo extensive growth and rewiring as they develop. Neurons transplanted at such an early stage should have the best chance of being integrated with the rats’ own brain circuits, Pașca reasoned.

The team used organoids made from skin cells. These cells were made into stem cells in the lab before being encouraged to form layers of cells that resemble those in the human cortex, the folded outer part of the brain that contains regions responsible for thought, vision, hearing, memory, and sensing the environment, among other things. This process took around two months in the lab. The resulting three-dimensional organoids were then injected into the brains of days-old rats through an incision in the skull. The organoids were transplanted into the sensory cortex, a region that plays a role in helping animals sense their environment.

Within four months, brain scans showed that the organoids had grown to around nine times their original volume—and made up around a third of one brain hemisphere. The cells appeared to have formed connections with rat brain cells and been incorporated into brain circuits.

How to Diagnose Alzheimer’s Through Retina

The onset of Alzheimer’s disease can be diagnosed by examining proteins in the retina instead of complicated and invasive PET scans or cerebrospinal fluid analysis. Alzheimer’s disease – the progressive neurological disorder that causes the brain to shrink and brain cells to die – is the most common cause of dementia. The disease causes a continuous decline in thinking, behavior and social skills that affect a person’s ability to function independently.

But while the disorder is incurable, it is important to diagnose it as rapidly as possible so measures can be taken to slow the decline. Doctors hope to eventually develop treatments to reduce the risk of developing Alzheimer’s disease.

But now, doctors in the ophthalmology department of the Samson Assuta-Ashdod University Hospital suggest a much simpler way to diagnose Alzheimer’s – by looking for beta-amyloid plaques and abnormal tau proteins in the retina of the eye. The advantage is the accessibility of the retina for direct visualization by non-invasive means.

The retina is a component of the central nervous system that can easily be accessed by technology used routinely by ophthalmologists, they wrote. Photoreceptors in this “screen” at the back of the eye absorb light and transfer data to the retinal ganglion cell layer. Axons (long, slender nerve fibers) in this layer accumulate along the retinal nerve fiber layer and transfer the data to the brain via the optic nerve connected to the eye.

Since the retina is connected to the brain, it seems that changes in this part of the eye reflect pathological processes in the brain, the authors wrote, including the development of Alzheimer’s disease. Amyloid-beta plaques have been found in the retina of cadavers in autopsies of people who died of Alzheimer’s.

Turmeric is a natural, intensely yellow-colored spice that attaches itself to plaques of amyloid-beta. Ten Alzheimer’s patients and six healthy controls were asked to swallow turmeric capsules. A few days later, their retinas were examined. The yellow spice was found to stick to the retinal cells in Alzheimer’s patients but not in the healthy controlsOther non-invasive tests of the retina – including optical coherence tomography and optical coherence tomography angiography – were also conducted and found to point to the early development of Alzheimer’s, the authors wrote. Still, larger tests must be conducted with these means before they can be implemented clinically. A clear biomarker must also be found in the individual to be sure the patient is developing Alzheimer’s and sent for treatments, they concluded.

The research, just published in the latest issue of Harefuah – the Hebrew-language journal of the Israel Medical Association – was conducted by Drs. Keren Wood of the Samson Assuta Ashdod Hospital and Ben-Gurion University of the Negev, Idit Maharshak of Wolfson Medical Center in Holon and Tel Aviv University’s Sackler Faculty of Medicine, and Yosef Koronyo and Maya Koranyo-Hamaoui of the Cedars-Sinai Medical Center in Los Angeles, California.

Source: https://www.jpost.com/

How to Train AI to Generate Medicines and Vaccines

Scientists have developed artificial intelligence software that can create proteins that may be useful as vaccines, cancer treatments, or even tools for pulling carbon pollution out of the air. This research was led by the University of Washington School of Medicine and Harvard University.

The proteins we find in nature are amazing molecules, but designed proteins can do so much more,” said senior author David Baker, a professor of biochemistry at UW Medicine. “In this work, we show that machine learning can be used to design proteins with a wide variety of functions.

For decades, scientists have used computers to try to engineer proteins. Some proteins, such as antibodies and synthetic binding proteins, have been adapted into medicines to combat COVID-19. Others, such as enzymes, aid in industrial manufacturing. But a single protein molecule often contains thousands of bonded atoms; even with specialized scientific software, they are difficult to study and engineer. Inspired by how machine learning algorithms can generate stories or even images from prompts, the team set out to build similar software for designing new proteins. “The idea is the same: neural networks can be trained to see patterns in data. Once trained, you can give it a prompt and see if it can generate an elegant solution. Often the results are compelling — or even beautiful,” said lead author Joseph Watson, a postdoctoral scholar at UW Medicine.

The team trained multiple neural networks using information from the Protein Data Bank, which is a public repository of hundreds of thousands of protein structures from across all kingdoms of life. The neural networks that resulted have surprised even the scientists who created them.

Deep machine learning program hallucinating new ideas for vaccine molecules

The team developed two approaches for designing proteins with new functions. The first, dubbed “hallucination” is akin to DALL-E or other generative A.I. tools that produce new output based on simple prompts. The second, dubbed “inpainting,” is analogous to the autocomplete feature found in modern search bars and email clients.

Most people can come up with new images of cats or write a paragraph from a prompt if asked, but with protein design, the human brain cannot do what computers now can,” said lead author Jue Wang, a postdoctoral scholar at UW Medicine. “Humans just cannot imagine what the solution might look like, but we have set up machines that do.

To explain how the neural networkshallucinate’ a new protein, the team compares it to how it might write a book: “You start with a random assortment of words — total gibberish. Then you impose a requirement such as that in the opening paragraph, it needs to be a dark and stormy night. Then the computer will change the words one at a time and ask itself ‘Does this make my story make more sense?’ If it does, it keeps the changes until a complete story is written,” explains Wang.

Both books and proteins can be understood as long sequences of letters. In the case of proteins, each letter corresponds to a chemical building block called an amino acid. Beginning with a random chain of amino acids, the software mutates the sequence over and over until a final sequence that encodes the desired function is generated. These final amino acid sequences encode proteins that can then be manufactured and studied in the laboratory.

The research is published in the journal Science.

Source: https://newsroom.uw.edu/

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/

Milking Cow Cells in a Lab for Animal-Free Dairy

In a lab in Boston, a startup has spent the last few months cultivating mammary cells from a cow—and recently succeeded in finding the perfect conditions to get those cells to produce real cow milk without an animal.  “We spend a lot of time trying to understand how the biology works in a cow, and then trying to do that,” says Sohail Gupta, CEO and cofounder of the startup, called Brown Foods, which makes a product that it calls UnReal Milk.

The startup, which operates in India and the U.S., just completed a stint at the tech accelerator Y Combinator. Alternative-dairy sales keep growing: In 2020, according to the most recent data available, sales of oat, soy, almond, and other alt-milk products made up 15% of all milk sales in the U.S., a 27% growth over the previous two years. But Brown Foods, like others in the space, recognized that plant-based milk still can’t replicate traditional dairy.

They’re not yet there in terms of taste and texture,” Gupta says. They also often have less protein and other nutrients. He argues that other new milk alternatives, including those that use precision fermentation to make animal-free dairy proteins, also can’t perfectly match dairy since they still use plant ingredients for fat and other components. There are multiple reasons to move away from traditional dairy, including the fact that cows raised for milk and meat are responsible for around 30% of the world’s emissions of methane,a potent greenhouse gas. But Gupta thinks that it makes sense to stay as close to the natural process as possible. Mammary cells “have evolved naturally over centuries to produce milk in mammals,” he says. “So these cells have the entire genetic architecture to produce the fats, the carbs, the proteins.

The company’s biochemical engineers have been studying how the cells behave, what they need nutritionally to survive, and what triggers lactation. “We’re trying to emulate nature and understand what kind of chemical signals are released in a mammal to trigger the cells to lactate and start secreting milk and get into the lactation phase,” he says. Now that they’ve shown that it can work at the small scale in the lab, they’re beginning to prepare for commercial production in larger bioreactors. The company believes that it can eventually reach price parity with conventional milk. In early calculations, it says that it could cut the greenhouse gas emissions from milk by 90%. (Unlike lab-grown meat, which requires an energy-intensive process of growing cells, producing milk just requires keeping cells alive, and has a far smaller footprint.)

Source: https://www.fastcompany.com/

27 Proteins that May Predict Heart Disease Risk

In a new study, scientists have reported findings that show a blood test can be used to predict Cardiac Vascular Disease (CVD). The research, published in the journal Science Translational Medicine, opens the door to more individualized treatment plans for CVD. It may also improve the speed at which new CVD drugs can be identified and developed. When a new drug is developed, scientists have to make sure that it is both effective and safe. This is a rigorous process that can often take many years. While important, this significantly slows down the speed at which new drugs can be developed, and also increases the costs.

One way of increasing the speed and reducing the cost of drug development without sacrificing efficacy or safety is to use a surrogate biomarker as a predictor of risk. If a surrogate can reliably predict risk, then some stages of clinical trials can be streamlinedFinding a surrogate that can accurately predict the risk of certain diseases can also benefit patients directly. If a clinician can measure a reliable surrogate they can potentially prevent a disease before it has developed, reducing the risks to the patient.

For situations where clinical cardiovascular outcomes studies are required today, a surrogate enables unsafe or ineffective candidate drugs to be terminated early and cheaply and supports the acceleration of safe and effective drugs. Participants in the trials do not have to have events or die in order to contribute to the signal.” said Dr. Stephen Williams — Chief Medical Officer at SomaLogic, and the corresponding author of the present study. “In personalized medicine, a surrogate enables cost-effective allocation of treatments to the people who need them the most, and potentially increases the uptake of newer more effective drugs so that outcomes are improved,” said Dr. Williams.

In 2004 the United States Food and Drug Administration (FDA) published a report Trusted Source recommending that researchers identify biomarker surrogates that could help in CVD drug development and improve individualized patient care.

Nano-Robots Injected into your Bloodstream to Fight Disease

What if there was a magical robot that could cure any disease? Don’t answer that. It’s a stupid question. Everyone knows there’s no one machine that could do that. But maybe a swarm made up of tens of thousands of tiny autonomous micro-bots could? That’s the premise laid out by proponents of nanobot medical technology. In science fiction, the big idea usually involves creating tiny metal robots via some sort of magic-adjacent miniaturization technology.

Luckily for us, the reality of nanobot tech is infinitely cooler. A team of researchers from Australia have developed a mind-blowing prototype that could work as a proof-of-concept for the future of medicine. Called “autonomous molecular machines,” the new nanotechnology eschews the traditional visage of microscopic metal automatons in favor of a more natural approach.

Inspired by biology, we design and synthesize a DNA origami receptor that exploits multivalent interactions to form stable complexes that are also capable of rapid subunit exchange”, explained the researchers. “DNA nanobots are synthetic nanometer-sized machines made of DNA and proteins. They’re autonomous because DNA itself is a self-assembling machine. Our natural DNA not only carries the code our biology is written in, it also knows when to execute. That’s part of the reason why, for example, your left and right feet tend to grow at roughly the same rate.”

Previous work in the field of DNA nanotechnology has demonstrated self-assembling machines capable of transferring DNA code, much like their natural counterparts. But the new tech out of Australia is unlike anything we’ve ever seen before.
Using the DNA origami receptor to demonstrate stable interactions with rapid exchange of both DNA and protein subunits, thus highlighting the applicability of the approach to arbitrary molecular cargo, an important distinction with canonical toehold exchange between single-stranded DNA. These particular nanobots can transfer more than just DNA information. Theoretically speaking, they could deliver any conceivable combination of proteins throughout a given biological system. To put that in simpler terms: the scientists should be able to eventually program swarms of these nanobots to hunt down bacteria, viruses, and cancer cells inside of our bodies. Each member of the swarm could carry a specific protein and, when they’ve found a bad cell, they could assemble their proteins into a formation designed to eliminate the threat.

Source: https://thenextweb.com/