Category Archives: Pennsylvania Stem Cells

Blood vessels are supposed to act like trees, pumping in oxygen tissues need to grow and immune cells required to clear out pathogens. But in tumors, the forest can go a bit haywire. Vessels grow prodigiously and bulge and twist at abrupt points, making it difficult to even tell whats a vein and whats an artery. It starts to look less like a forest and more like a gnarled root floor. A disorganized labyrinth, one oncologist has called it.

For cancer, chaos is a virtue. That gnarled root floor insulates solid tumors from immune cells and, in recent years, has flustered drug developers best attempts at developing therapies meant to rev up the immune system and direct it toward the tumors.

Researchers at the University of Pennsylvania, however, think they may have stumbled onto a solution, a way of whipping the blood vessels back into proper shape. If it works, experts say, it could pave the way for CAR-T treatments that attack solid tumors and potentially improve the effectiveness for more traditional approaches, such as radiation and chemotherapy.

Its a really novel and potentially important approach, Patrick Wen, a neuro-oncologist at Dana-Farber who was not involved in the work, told Endpoints News. They really did good work. This is a very different way of improving immunotherapy.

Yi Fan, a radiation oncologist at Penns School of Medicine, has been working for the last few years to understand why the labyrinth appears in the first place. Researchers had previously circled in on the so-called growth factors that stimulate blood vessel formation. Attempts to block these factors, though, disappointed; Avastin, an antibody against the factor VEGF, became a blockbuster but has continually failed to improve survival on a range of malignancies.

Scientists would have to go more fundamental. In a pair of 2018 papers, Fan showed that part of the problem is a process called endothelial cell transformation. Cells lining the blood vessels around the tumor acquire stem cell-like properties that allow them to reproduce and expand rapidly, as stem cells do.

Theres a genetic reprogramming, Fan told Endpoints. Theyll become really aggressive.

But how did that reprogramming happen? If Fan could pin down the pathway, he figured he could then devise a way to block it. He started knocking out kinases the cellular engines that can drive epigenetic change, or reprogramming one by one in endothelial cells isolated from patients with an aggressive brain cancer called glioblastoma. Out of 518, 35 prevented transformation and one did so particularly well: PAK4.

Then they injected tumors into mice, some who had PAK4 and some who had the kinase genetically removed: Eighty percent of the mice who had PAK4 removed lived for 60 days, while all of the wild-type mice died within 40. Fans team also showed that T cells infiltrated the tumors more easily in the PAK4-less mice.

It was a fortuitous finding: Drug companies had developed several PAK inhibitors a decade ago, when kinase inhibitors were the flashiest thing in pharma. Many had been abandoned, but Karyopharm had recently brought a PAK4 blocker into Phase I.

To see whether drug developers could exploit this finding, Fan and his team removed T cells from mice and developed a CAR-T therapy to attack the tumors.

They gave mice three different regimens. The CAR-T therapy on its own failed to reduce tumor size, apparently unable to reach through the vessels. The Karyopharm drug also had little effect on its own. But combined, they managed to reduce tumor size by 80% after five days. They published the results in Nature Cancer this week.

It is a really eye-opening result, Fan said. I think we see something really dramatic.

That, of course, is just in mice, but Fan already has strong supporting evidence for PAK4s role in cancer. Last December, while Fan was still completing his experiment, Nature Cancer published a paper from Antoni Ribas UCLA lab suggesting that PAK4 inhibitors can help T cells infiltrate around various solid tumors. They showed that the same Karyopharm inhibitor could boost the effects of PD-1 inhibitors in mice, allowing activated T cells to better reach tumors.

That work has already translated into the clinic; weeks after it came out, Karyopharm added an arm to their Phase I study of the drug that will look at the PAK4 inhibitor in combination with the PD-1 blocker Opdivo.

Ribas said that Fans work is compelling and helps confirm the role of PAK4, but he said a CAR-T therapy would face a much longer path to the clinic. Its simply much easier to combine an approved drug with an experimental one than to devise a new CAR-T therapy, mix it with the unapproved inhibitor (and all the other things, such as bone marrow-clearing chemotherapy, CAR-T recipients receive) and then deduce what effect each is having.

It will a take a while, Ribas told Endpoints. But I hope this is right and its developed clinically.

There are also other unresolved obstacles for CAR-T in solid tumors, Wen said. Developers still struggle to find targets that wont also send the super-charged T cells after healthy tissue. And tangled blood vessels are just one of several mechanisms tumors have of defending themselves. They can, for example, turn tumor-eating immune cells into tumor-defending ones.

Still, Wen said, in the short term, the approach offered a path toward boosting the efficacy of radiation, chemotherapy and other small molecule drugs. Although Fan focused on glioblastoma, researchers agreed PAK4 likely plays the same vessel-warping role in many other solid tumors.

Theres a lot of things you could look at, he said.

In a January review, Jessica Fessler and Thomas Gajewski at the University of Chicago said Ribas paper pointed towards a path for improving PD-1 and overcoming resistance in some tumors. But they also raised questions about the Karyopharm drug, noting that it hits other proteins besides PAK4. That could mean other mechanisms are also at play and that the drug could affect other tissues in humans.

Ribas agreed that Karyopharms drug might not be the perfect molecule but said others could be on their way. He serves as a scientific advisor to Arcus, the Terry Rosen startup that is now working on developing its own PAK4 inhibitor.

If they can develop a very selective PAK4 inhibitor, he said, it may be a more direct way of testing the role of PAK4.

Tests with that drug, in turn, could help clear up a biological mystery that emerged out of Fans and Ribas papers. Although both investigators zeroed in on PAK4, each of them suggested very different mechanisms by which PAK4 kept immune cells out of the tumor. Ribas suggested it directly suppresses T cells, while Fan found it led to those transformations inside the blood vessels near the tumor.

Kinases are versatile proteins and both researchers said its possible that PAK4 is doing both. Its also possible, they said, that one is more important than the other, or simply that one of them is just wrong.

When you start with completely new biology, its hard to get it right the first time, Ribas said.

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Penn researchers find a way through the labyrinth keeping CAR-T from solid tumors - Endpoints News

A world-first light bulb moment discovery by a modest Queensland scientist could deliver the ultimate gift in modern science - a way to reverse the ageing process.

On a lab bench at the University of Queensland, Professor Justin Cooper-White, a chemical engineer, is working on an incredible project that will one day help peel back the years and allow older people to live a more youthful, active life and ultimately look younger.

This Benjamin Button-effect is just one of the areas of regenerative science that will change the world of healthcare.

"It's fantastical to think that a 70 year old will suddenly have the youth of a 20 year old that's not going to happen but there is very real evidence that it will be possible to slow ageing and revert cells in the body that are "frustrated" due to age into more calm cells that will allow easier movement, better breathing and faster healing," Prof Cooper-White said.

Professor Justin Cooper-White at UQs Robotic Stem Cell Engineering Facility.

"I can't say that people will look younger but it's possible. When a person is active and living life to the full they generally look better. The focus is not necessarily about prolonging life span, it's more about prolonging health span. Our work is not a silver bullet, exercise and nutrition will all play a part," he said.

Prof Cooper-White made the discovery that body tissues are not just elastic and solid but also work a bit like a liquid and now his team is investigating how the viscoelasticity of bodies change over time and ways to reverse the process.

"Viscoelasticity describes the way materials, like our skin, muscles, bones or even our organs, respond to being 'stressed', through pushing, pulling or shearing, the forces that our tissues experience in everyday life," he said.

"All tissues in the body are viscoelastic - it is an intrinsic property of them. We age because our body gets less viscoelastic. This is something we are focusing on now. Maybe it's just because I am getting older. As we age, daily ailments cause inflammation. Inflammation in one area is carried around the whole body by our blood vessels, causing the extracellular matrix of all our tissues to become stiff and corrupted, or 'fibrotic'. This corrupts the stem cell 'niches', the homes of stem cells that live next to our blood vessels," he said.

"We're investigating what happens when those tissues become less viscoelastic and how we might reverse that," Professor Cooper-White said.

Professor Cooper-White says allowing people to live full lives into old age would be a good investment.

Since the scientist and his team from UQ's Australian Institute for Bioengineering and Nanotechnology (AIBN) unit first flagged the importance of viscoelasticity on stem cell behaviours in 2011, researchers around the world have been working to confirm those findings and probe other related mechanical properties of cells, building an in-depth body of knowledge that can be used to inform biological, medical and engineering research.

"We have been working on the ageing area for the last four or five years and making progress," the professor said.

Late this year Prof Cooper-White joined the world's top tissue engineering experts from Stanford University, Harvard University and University of Pennsylvania to review the works investigating viscoelasticity.

The latest research in their field was published in the prestigious scientific journal Nature.

"There is a lot of work to be done and I would estimate we are talking at least a couple of decades before therapeutics would even be available. We would have to look at trials in small animals, larger animals and then human trials. But this is very important science. We are looking at a future where Australia will have a very high percentage of older people. It would make sense for more investment to be put into allowing older people to live life to the full and have a long health span. Doesn't that make more sense that putting all the money into programs to look after people after they end up decrepit?" the chemical engineer said.

"This has not come to the public eye as much as I would have expected it to, given how important it is," the professor said.

Brad Pitt in a scene from The Curious Case of Benjamin Button. Picture: AP Photo

It is predicted that almost one quarter of Australians will be over 65 by June 2050 and other countries will have an even bigger aged population.

"We are not talking about offering the fountain of life but regenerative science is a key area of research for the future. It's exciting what we have found so far," Prof Cooper-White said. Leading them into work in engineering of healthy ageing with stem cells, the team at UQ works on artificially creating new tissue like recreating breast tissue for women who have had a mastectomy. It was this work into body tissues that lead to the professor's world stopping discovery in regenerative medicine.

Originally published as 'Benjamin Button' discovery could reverse ageing process

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'Benjamin Button' discovery could reverse ageing process - Queensland Times

ANDOVER, Mass. The liquid that many hope could help end the Covid-19 pandemic is stored in a nondescript metal tank in a manufacturing complex owned by Pfizer, one of the worlds biggest drug companies. There is nothing remarkable about the container, which could fit in a walk-in closet, except that its contents could end up in the worlds first authorized Covid-19 vaccine.

Pfizer, a 171-year-old Fortune 500 powerhouse, has made a billion-dollar bet on that dream. So has a brash, young rival just 23 miles away in Cambridge, Mass. Moderna, a 10-year-old biotech company with billions in market valuation but no approved products, is racing forward with a vaccine of its own. Its new sprawling drug-making facility nearby is hiring workers at a fast clip in the hopes of making history and a lot of money.

In many ways, the companies and their leaders couldnt be more different. Pfizer, working with a little-known German biotech called BioNTech, has taken pains for much of the year to manage expectations. Moderna has made nearly as much news for its stream of upbeat press releases, executives stock sales, and spectacular rounds of funding as for its science.

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Each is well-aware of the other in the race to be first.

But what the companies share may be bigger than their differences: Both are banking on a genetic technology that has long held huge promise but has so far run into biological roadblocks. It is called synthetic messenger RNA, an ingenious variation on the natural substance that directs protein production in cells throughout the body. Its prospects have swung billions of dollars on the stock market, made and imperiled scientific careers, and fueled hopes that it could be a breakthrough that allows society to return to normalcy after months living in fear.

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Both companies have been frequently name-checked by President Trump. Pfizer reported strong, but preliminary, data on Monday, and Moderna is expected to follow suit soon with a glimpse of its data. Both firms hope these preliminary results will allow an emergency deployment of their vaccines millions of doses likely targeted to frontline medical workers and others most at risk of Covid-19.

There are about a dozen experimental vaccines in late-stage clinical trials globally, but the ones being tested by Pfizer and Moderna are the only two that rely on messenger RNA.

For decades, scientists have dreamed about the seemingly endless possibilities of custom-made messenger RNA, or mRNA.

Researchers understood its role as a recipe book for the bodys trillions of cells, but their efforts to expand the menu have come in fits and starts. The concept: By making precise tweaks to synthetic mRNA and injecting people with it, any cell in the body could be transformed into an on-demand drug factory.

But turning scientific promise into medical reality has been more difficult than many assumed. Although relatively easy and quick to produce compared to traditional vaccine-making, no mRNA vaccine or drug has ever won approval.

Even now, as Moderna and Pfizer test their vaccines on roughly 74,000 volunteers in pivotal vaccine studies, many experts question whether the technology is ready for prime time.

I worry about innovation at the expense of practicality, Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and an authority on vaccines, said recently. The U.S. governments Operation Warp Speed program, which has underwritten the development of Modernas vaccine and pledged to buy Pfizers vaccine if it works, is weighted toward technology platforms that have never made it to licensure before.

Whether mRNA vaccines succeed or not, their path from a gleam in a scientists eye to the brink of government approval has been a tale of personal perseverance, eureka moments in the lab, soaring expectations and an unprecedented flow of cash into the biotech industry.

It is a story that began three decades ago, with a little-known scientist who refused to quit.

Before messenger RNA was a multibillion-dollar idea, it was a scientific backwater. And for the Hungarian-born scientist behind a key mRNA discovery, it was a career dead-end.

Katalin Karik spent the 1990s collecting rejections. Her work, attempting to harness the power of mRNA to fight disease, was too far-fetched for government grants, corporate funding, and even support from her own colleagues.

It all made sense on paper. In the natural world, the body relies on millions of tiny proteins to keep itself alive and healthy, and it uses mRNA to tell cells which proteins to make. If you could design your own mRNA, you could, in theory, hijack that process and create any protein you might desire antibodies to vaccinate against infection, enzymes to reverse a rare disease, or growth agents to mend damaged heart tissue.

In 1990, researchers at the University of Wisconsin managed to make it work in mice. Karik wanted to go further.

The problem, she knew, was that synthetic RNA was notoriously vulnerable to the bodys natural defenses, meaning it would likely be destroyed before reaching its target cells. And, worse, the resulting biological havoc might stir up an immune response that could make the therapy a health risk for some patients.

It was a real obstacle, and still may be, but Karik was convinced it was one she could work around. Few shared her confidence.

Every night I was working: grant, grant, grant, Karik remembered, referring to her efforts to obtain funding. And it came back always no, no, no.

By 1995, after six years on the faculty at the University of Pennsylvania, Karik got demoted. She had been on the path to full professorship, but with no money coming in to support her work on mRNA, her bosses saw no point in pressing on.

She was back to the lower rungs of the scientific academy.

Usually, at that point, people just say goodbye and leave because its so horrible, Karik said.

Theres no opportune time for demotion, but 1995 had already been uncommonly difficult. Karik had recently endured a cancer scare, and her husband was stuck in Hungary sorting out a visa issue. Now the work to which shed devoted countless hours was slipping through her fingers.

I thought of going somewhere else, or doing something else, Karik said. I also thought maybe Im not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.

In time, those better experiments came together. After a decade of trial and error, Karik and her longtime collaborator at Penn Drew Weissman, an immunologist with a medical degree and Ph.D. from Boston University discovered a remedy for mRNAs Achilles heel.

The stumbling block, as Kariks many grant rejections pointed out, was that injecting synthetic mRNA typically led to that vexing immune response; the body sensed a chemical intruder, and went to war. The solution, Karik and Weissman discovered, was the biological equivalent of swapping out a tire.

Every strand of mRNA is made up of four molecular building blocks called nucleosides. But in its altered, synthetic form, one of those building blocks, like a misaligned wheel on a car, was throwing everything off by signaling the immune system. So Karik and Weissman simply subbed it out for a slightly tweaked version, creating a hybrid mRNA that could sneak its way into cells without alerting the bodys defenses.

That was a key discovery, said Norbert Pardi, an assistant professor of medicine at Penn and frequent collaborator. Karik and Weissman figured out that if you incorporate modified nucleosides into mRNA, you can kill two birds with one stone.

That discovery, described in a series of scientific papers starting in 2005, largely flew under the radar at first, said Weissman, but it offered absolution to the mRNA researchers who had kept the faith during the technologys lean years. And it was the starter pistol for the vaccine sprint to come.

And even though the studies by Karik and Weissman went unnoticed by some, they caught the attention of two key scientists one in the United States, another abroad who would later help found Moderna and Pfizers future partner, BioNTech.

Derrick Rossi, a native of Toronto who rooted for the Maple Leafs and sported a soul patch, was a 39-year-old postdoctoral fellow in stem cell biology at Stanford University in 2005 when he read the first paper. Not only did he recognize it as groundbreaking, he now says Karik and Weissman deserve the Nobel Prize in chemistry.

If anyone asks me whom to vote for some day down the line, I would put them front and center, he said. That fundamental discovery is going to go into medicines that help the world.

But Rossi didnt have vaccines on his mind when he set out to build on their findings in 2007 as a new assistant professor at Harvard Medical School running his own lab.

He wondered whether modified messenger RNA might hold the key to obtaining something else researchers desperately wanted: a new source of embryonic stem cells.

In a feat of biological alchemy, embryonic stem cells can turn into any type of cell in the body. That gives them the potential to treat a dizzying array of conditions, from Parkinsons disease to spinal cord injuries.

But using those cells for research had created an ethical firestorm because they are harvested from discarded embryos.

Rossi thought he might be able to sidestep the controversy. He would use modified messenger molecules to reprogram adult cells so that they acted like embryonic stem cells.

He asked a postdoctoral fellow in his lab to explore the idea. In 2009, after more than a year of work, the postdoc waved Rossi over to a microscope. Rossi peered through the lens and saw something extraordinary: a plate full of the very cells he had hoped to create.

Rossi excitedly informed his colleague Timothy Springer, another professor at Harvard Medical School and a biotech entrepreneur. Recognizing the commercial potential, Springer contacted Robert Langer, the prolific inventor and biomedical engineering professor at the Massachusetts Institute of Technology.

On a May afternoon in 2010, Rossi and Springer visited Langer at his laboratory in Cambridge. What happened at the two-hour meeting and in the days that followed has become the stuff of legend and an ego-bruising squabble.

Langer is a towering figure in biotechnology and an expert on drug-delivery technology. At least 400 drug and medical device companies have licensed his patents. His office walls display many of his 250 major awards, including the Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers.

As he listened to Rossi describe his use of modified mRNA, Langer recalled, he realized the young professor had discovered something far bigger than a novel way to create stem cells. Cloaking mRNA so it could slip into cells to produce proteins had a staggering number of applications, Langer thought, and might even save millions of lives.

I think you can do a lot better than that, Langer recalled telling Rossi, referring to stem cells. I think you could make new drugs, new vaccines everything.

Langer could barely contain his excitement when he got home to his wife.

This could be the most successful company in history, he remembered telling her, even though no company existed yet.

Three days later Rossi made another presentation, to the leaders of Flagship Ventures. Founded and run by Noubar Afeyan, a swaggering entrepreneur, the Cambridge venture capital firm has created dozens of biotech startups. Afeyan had the same enthusiastic reaction as Langer, saying in a 2015 article in Nature that Rossis innovation was intriguing instantaneously.

Within several months, Rossi, Langer, Afeyan, and another physician-researcher at Harvard formed the firm Moderna a new word combining modified and RNA.

Springer was the first investor to pledge money, Rossi said. In a 2012 Moderna news release, Afeyan said the firms promise rivals that of the earliest biotechnology companies over 30 years ago adding an entirely new drug category to the pharmaceutical arsenal.

But although Moderna has made each of the founders hundreds of millions of dollars even before the company had produced a single product Rossis account is marked by bitterness. In interviews with the Globe in October, he accused Langer and Afeyan of propagating a condescending myth that he didnt understand his discoverys full potential until they pointed it out to him.

Its total malarkey, said Rossi, who ended his affiliation with Moderna in 2014. Im embarrassed for them. Everybody in the know actually just shakes their heads.

Rossi said that the slide decks he used in his presentation to Flagship noted that his discovery could lead to new medicines. Thats the thing Noubar has used to turn Flagship into a big company, and he says it was totally his idea, Rossi said.

Afeyan, the chair of Moderna, recently credited Rossi with advancing the work of the Penn scientists. But, he said, that only spurred Afeyan and Langer to ask the question, Could you think of a code molecule that helps you make anything you want within the body?

Langer, for his part, told STAT and the Globe that Rossi made an important finding but had focused almost entirely on the stem cell thing.

Despite the squabbling that followed the birth of Moderna, other scientists also saw messenger RNA as potentially revolutionary.

In Mainz, Germany, situated on the left bank of the Rhine, another new company was being formed by a married team of researchers who would also see the vast potential for the technology, though vaccines for infectious diseases werent on top of their list then.

A native of Turkey, Ugur Sahin moved to Germany after his father got a job at a Ford factory in Cologne. His wife, zlem Treci had, as a child, followed her father, a surgeon, on his rounds at a Catholic hospital. She and Sahin are physicians who met in 1990 working at a hospital in Saarland.

The couple have long been interested in immunotherapy, which harnesses the immune system to fight cancer and has become one of the most exciting innovations in medicine in recent decades. In particular, they were tantalized by the possibility of creating personalized vaccines that teach the immune system to eliminate cancer cells.

Both see themselves as scientists first and foremost. But they are also formidable entrepreneurs. After they co-founded another biotech, the couple persuaded twin brothers who had invested in that firm, Thomas and Andreas Strungmann, to spin out a new company that would develop cancer vaccines that relied on mRNA.

That became BioNTech, another blended name, derived from Biopharmaceutical New Technologies. Its U.S. headquarters is in Cambridge. Sahin is the CEO, Treci the chief medical officer.

We are one of the leaders in messenger RNA, but we dont consider ourselves a messenger RNA company, said Sahin, also a professor at the Mainz University Medical Center. We consider ourselves an immunotherapy company.

Like Moderna, BioNTech licensed technology developed by the Pennsylvania scientist whose work was long ignored, Karik, and her collaborator, Weissman. In fact, in 2013, the company hired Karik as senior vice president to help oversee its mRNA work.

But in their early years, the two biotechs operated in very different ways.

In 2011, Moderna hired the CEO who would personify its brash approach to the business of biotech.

Stphane Bancel was a rising star in the life sciences, a chemical engineer with a Harvard MBA who was known as a businessman, not a scientist. At just 34, he became CEO of the French diagnostics firm BioMrieux in 2007 but was wooed away to Moderna four years later by Afeyan.

Moderna made a splash in 2012 with the announcement that it had raised $40 million from venture capitalists despite being years away from testing its science in humans. Four months later, the British pharmaceutical giant AstraZeneca agreed to pay Moderna a staggering $240 million for the rights to dozens of mRNA drugs that did not yet exist.

The biotech had no scientific publications to its name and hadnt shared a shred of data publicly. Yet it somehow convinced investors and multinational drug makers that its scientific findings and expertise were destined to change the world. Under Bancels leadership, Moderna would raise more than $1 billion in investments and partnership funds over the next five years.

Modernas promise and the more than $2 billion it raised before going public in 2018 hinged on creating a fleet of mRNA medicines that could be safely dosed over and over. But behind the scenes the companys scientists were running into a familiar problem. In animal studies, the ideal dose of their leading mRNA therapy was triggering dangerous immune reactions the kind for which Karik had improvised a major workaround under some conditions but a lower dose had proved too weak to show any benefits.

Moderna had to pivot. If repeated doses of mRNA were too toxic to test in human beings, the company would have to rely on something that takes only one or two injections to show an effect. Gradually, biotechs self-proclaimed disruptor became a vaccines company, putting its experimental drugs on the back burner and talking up the potential of a field long considered a loss-leader by the drug industry.

Meanwhile BioNTech has often acted like the anti-Moderna, garnering far less attention.

In part, that was by design, said Sahin. For the first five years, the firm operated in what Sahin called submarine mode, issuing no news releases, and focusing on scientific research, much of it originating in his university lab. Unlike Moderna, the firm has published its research from the start, including about 150 scientific papers in just the past eight years.

In 2013, the firm began disclosing its ambitions to transform the treatment of cancer and soon announced a series of eight partnerships with major drug makers. BioNTech has 13 compounds in clinical trials for a variety of illnesses but, like Moderna, has yet to get a product approved.

When BioNTech went public last October, it raised $150 million, and closed with a market value of $3.4 billion less than half of Modernas when it went public in 2018.

Despite his role as CEO, Sahin has largely maintained the air of an academic. He still uses his university email address and rides a 20-year-old mountain bicycle from his home to the office because he doesnt have a drivers license.

Then, late last year, the world changed.

Shortly before midnight, on Dec. 30, the International Society for Infectious Diseases, a Massachusetts-based nonprofit, posted an alarming report online. A number of people in Wuhan, a city of more than 11 million people in central China, had been diagnosed with unexplained pneumonia.

Chinese researchers soon identified 41 hospitalized patients with the disease. Most had visited the Wuhan South China Seafood Market. Vendors sold live wild animals, from bamboo rats to ostriches, in crowded stalls. That raised concerns that the virus might have leaped from an animal, possibly a bat, to humans.

After isolating the virus from patients, Chinese scientists on Jan. 10 posted online its genetic sequence. Because companies that work with messenger RNA dont need the virus itself to create a vaccine, just a computer that tells scientists what chemicals to put together and in what order, researchers at Moderna, BioNTech, and other companies got to work.

A pandemic loomed. The companies focus on vaccines could not have been more fortuitous.

Moderna and BioNTech each designed a tiny snip of genetic code that could be deployed into cells to stimulate a coronavirus immune response. The two vaccines differ in their chemical structures, how the substances are made, and how they deliver mRNA into cells. Both vaccines require two shots a few weeks apart.

The biotechs were competing against dozens of other groups that employed varying vaccine-making approaches, including the traditional, more time-consuming method of using an inactivated virus to produce an immune response.

Moderna was especially well-positioned for this moment.

Forty-two days after the genetic code was released, Modernas CEO Bancel opened an email on Feb. 24 on his cellphone and smiled, as he recalled to the Globe. Up popped a photograph of a box placed inside a refrigerated truck at the Norwood plant and bound for the National Institute of Allergy and Infectious Diseases in Bethesda, Md. The package held a few hundred vials, each containing the experimental vaccine.

Moderna was the first drug maker to deliver a potential vaccine for clinical trials. Soon, its vaccine became the first to undergo testing on humans, in a small early-stage trial. And on July 28, it became the first to start getting tested in a late-stage trial in a scene that reflected the firms receptiveness to press coverage.

The first volunteer to get a shot in Modernas late-stage trial was a television anchor at the CNN affiliate in Savannah, Ga., a move that raised eyebrows at rival vaccine makers.

Along with those achievements, Moderna has repeatedly stirred controversy.

On May 18, Moderna issued a press release trumpeting positive interim clinical data. The firm said its vaccine had generated neutralizing antibodies in the first eight volunteers in the early-phase study, a tiny sample.

But Moderna didnt provide any backup data, making it hard to assess how encouraging the results were. Nonetheless, Modernas share price rose 20% that day.

Some top Moderna executives also drew criticism for selling shares worth millions, including Bancel and the firms chief medical officer, Tal Zaks.

In addition, some critics have said the government has given Moderna a sweetheart deal by bankrolling the costs for developing the vaccine and pledging to buy at least 100 million doses, all for $2.48 billion.

That works out to roughly $25 a dose, which Moderna acknowledges includes a profit.

In contrast, the government has pledged more than $1 billion to Johnson & Johnson to manufacture and provide at least 100 million doses of its vaccine, which uses different technology than mRNA. But J&J, which collaborated with Beth Israel Deaconess Medical Centers Center for Virology and Vaccine Research and is also in a late-stage trial, has promised not to profit off sales of the vaccine during the pandemic.

Over in Germany, Sahin, the head of BioNTech, said a Lancet article in January about the outbreak in Wuhan, an international hub, galvanized him.

We understood that this would become a pandemic, he said.

The next day, he met with his leadership team.

I told them that we have to deal with a pandemic which is coming to Germany, Sahin recalled.

He also realized he needed a strong partner to manufacture the vaccine and thought of Pfizer. The two companies had worked together before to try to develop mRNA influenza vaccines. In March, he called Pfizers top vaccine expert, Kathrin Jansen.

Go here to read the rest:
The story of mRNA: From a loose idea to a tool that may help curb Covid - STAT

Dr. Andreas Sauerbrey believes the most important factor in getting efficient and correct orthopaedic treatment is having the right diagnosis.

You need to come to a specialist who can give you the options for that diagnosis, he said.

Dr. Sauerbrey, who specializes in shoulder and upper-extremity surgery, sports medicine, and joint restoration at Steamboat Orthopaedic and Spine Institute (SOSI), is proud of the access the institute provides to so many fellowship-trained surgeons. This extra level of training and experience provides the community with orthopaedic care that is truly world class.

When you come to see us, youll get the right diagnosis, but it doesnt mean you have to have surgery, he said.

Shoulder, elbow and hand

Dr. Sauerbrey is fellowship trained in shoulder and elbow surgery from the University of Pennsylvania and in hand surgery from Thomas Jefferson University in Philadelphia. He also holds a Sports Medicine Specialty Certificate.

Dr. Sauerbrey is particularly skilled in shoulder arthroscopy and reconstruction, and biologic treatments such as platelet-rich plasma (PRP) and growth factors.

For the past 20 years, Dr. Sauerbrey has performed 300 to 400 shoulder surgeries annually. He does just about every orthopaedic procedure, including knee and hip replacements, but about 60% of his work focuses on shoulders.

People have options within our practice, he said. If they dont come see me, they should see one of my partners. Theres really no reason to go out of town.

A progressive approach

Dr. Sauerbrey has been performing PRP injections since 2008. Hes particularly enthusiastic about how biomedicine has evolved in orthopaedic medicine during that time.

The biggest changes in orthopaedic medicine have been in biologics its just blown up in the last 10 years, he said.

Dr. Sauerbrey works with some of the most advanced orthopaedic companies to deliver the latest methods and treatments, which include PRP and stem cells.

The companies we use are very progressive, surgeon-driven, constantly innovating, he says. Its remarkable how much is out there, and SOSI offers it all.

PRP, the most popular injection, releases growth factors that trick the body into creating a healing response. Dr. Sauerbrey says he frequently does PRP injections in knees, shoulders and elbows. While its not going to fix mechanical injuries (such as an ACL tear), PRP, when used in the right context, can relieve pain and improve mobility.

My intention is to bring state-of-the-art medicine to Steamboat in an efficient and affordable way, he said. Together, we ensure the latest, most innovative technology available for both operative and non-operative procedures. We believe patients and their families should have the best care possible at all times.

Destined for orthopaedics

Dr. Sauerbreys brain was always mechanically oriented, so its no surprise he chose a medical field that would allow him to practice that skill on the human body.

Being good with your hands you either have it or you dont, he said. For me, it probably goes back to the days of wrenching on cars with my dad.

One of the first major decisions that medical students make about their future careers is whether they will become surgeons. For Sauerbrey, that happened by his second year of medical school. Having a mother who worked as an orthopaedic nurse for 20 years and getting the mechanical practice he did while working with his father, Sauerbrey was practically destined to become an orthopaedic surgeon.

I knew I had to do procedures, he said. Once you decide that, it eliminates half the field of potential specialties.

Community driven

With a belief that good health care should never be hard to find, Dr. Sauerbrey has committed himself to building an orthopaedic practice that puts the community first. Most of the SOSI physicians have been practicing in Yampa Valley for many years, and thats a testament to their high quality of care.

You cannot survive in a community like this if youre not doing a good job its not going to happen, he says. Youre operating on your friends and neighbors, and you have to be comfortable with that.

With an extremely active and motivated population that demands to be fixed back up so that they can return to their beloved outdoor activities, theres a real motivation to help patients get through their injuries and come out stronger on the other side.

We fix people so they can go back to what they love, Dr. Sauerbrey said. Were accountable socially here in Steamboat.

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New Delhi: Human immunity and its components have never been the topic of such breathless discussion for such a long time. But then, there has never been a time like the Covid-19 pandemic.

Between serological surveys (that check the level of antibodies against the SARS-CoV-2 virus in blood), rapid antigen tests (that test for the part of the virus that kickstarts immune mechanisms) and the quest for vaccines, the immune system is very much in.

That is also why lymphocytes (a class of white blood cells), especially the ones known as T-cells are the flavour of the season. They are probably the single most important component of the immune system; though given the perfectly synchronised working of the defence mechanism of the body, it may be a little unfair to designate any one as more important than the another.

T-cells play a plethora of roles in immunity as killer cells that can attack an infected cell and kill it along with the infecting agent, and as suppressor cells that modulate the level of functioning of other lymphocytes. They also have a starring role in the production of antibodies, a function performed by the other variant of lymphocytes called the B cells.

Latest research in Nature shows that presence of T-cells from earlier encounters with coronaviruses could have an important role to play in the bodys immune response, and therefore, a better understanding of it is crucial for the development of a vaccine.

The published data discussed here indicate that patients with severe COVID-19 can have either insufficient or excessive T cell responses. It is possible, therefore, that disease might occur in different patients at either end of this immune response spectrum, in one case from virus-mediated pathology and in the other case from T cell-driven immunopathology.

However, it is unclear why some patients respond too little and some patients too much, and whether the strength of the T cell response in the peripheral blood reflects the T cell response intensity in the respiratory tract and other SARS-CoV-2-infected organs, wrote the researchers from the University of Pennsylvania. They called for more research on the topic.

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Turns out, antibodies may or may not last, but T-cells are the new superheroes with the potential to possibly save the planet.

Also read: T Cells the unsung immune warriors that takeover after coronavirus antibodies wane

Immunity is of two kinds innate and acquired.

The defence mechanisms that the body is born with is known an innate immunity. This includes something as simple as the ability of the skin to prevent inner, more vulnerable tissues, from coming in contact with the external environment.

Acquired immunity, as the name suggests, is something that develops over time through exposure to pathogens or disease causing agents like virus and bacteria. Acquired immunity kicks in either through antibodies (this is known as humoral immunity) or through cells programmed to destroy invading organisms by causing the dissolution of the very cells that have been infected.

White blood cells (WBC) play a crucial role in immunity. There are five different kinds of WBCs eosinophil, basophil, neutrophil, monocyte and lymphocyte. Among these, the most important are lymphocytes, which include the T lymphocytes and the B lymphocytes. However, the others also have important roles to play as supporting cast. For the present discussion, we are concentrating on lymphocytes.

Also read: Immunity boosters are a myth why you shouldnt believe claims that promise to fight Covid

Structurally, under a microscope, very little differentiates a T-lymphocyte from a B lymphocyte. Both varieties are formed in the bone marrow from stem cells, get trained in different organs and then lodge themselves in the lymph nodes from where they are deployed when the occasion arises.

The training is important. It teaches the cells not to start attacking the bodys own cells. T-cells get trained antenatally (during pregnancy) and for some time after that in the thymus, a small gland present between the lungs only till puberty. B cells are trained in the foetal liver and bone marrow.

When a pathogen invades, specific chemicals unique to it (often proteins or complex carbohydrates) activate the bodys immune system. This activator, which is a unique feature of the invading pathogen, is the antigen. This is what the rapid antigen test looks for.

When an antigen has been detected, the T-cells troop out of the lymph node in an activated form and travel to the affected areas to take on the infection. The activated cells, called the Killer T cells, attach themselves to the membrane of the infected cell and with help of cytotoxic chemicals, kill the cell and destroy the invader with it. This is cell-mediated immunity. It is the basis of what happens when transplanted organs are rejected.

The thymus training teaches T-cells to ignore the antigens that are present within the body and not attack them. When that lesson is forgotten, because of genetic or environmental reasons, an autoimmune disorder is triggered.

Antigens set in motion a different pathway in the B lymphocytes. These enlarge and start duplicating very rapidly to form many clones, all of which, on maturity, start producing antibodies. The whole process happens very fast.

Antibodies are protein molecules that are present in the plasma, the matrix of the blood in which the cells float. Not all T-cells though turn into cytotoxic killers. Some become what are known as helper T cells, to go and further activate B lymphocytes to produce antibodies. In fact, without these helper cells, the antibody output is not quite sufficient to combat the invading particle.

Antibodies can directly kill the invader using a number of different mechanisms at their disposal. They can also activate a set of proteins present in the blood plasma that in turn can attack the invader using their own pathways.

Once the infection has been tackled, some of the B lymphocytes are tucked away with information about how this was done. These are memory cells that remain dormant until the next invasion happens. These ensure that when an infection recurs, the response is expedited, magnified and is longer lasting. This is the principle behind vaccination to teach the body to identify and combat a pathogen so that when a future infection happens, the response is stronger.

Also read:An Oxford immunologist breaks down how the universitys vaccine works against Covid-19

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T cells, B cells and the range of the human bodys immune response A simple decoder - ThePrint

While humans are all too familiar with the ravages of getting older, many trees seem to handle ageing a lot better.

Certain trees can live for thousands of years and appear to be immortal.

But not everyone is convinced these old timers can escape death due to old age.

Regardless, could humans with their relatively puny lifespans have something to learn from these ancient trees? Some scientists think so.

Establishing how old the oldest living tree is depends a bit on which plants are in the running for the title.

You could argue that Australia's Wollemi pine, which has been cloning itself for more than 60 million years, deserves the title. But that's kind of cheating because this involves multiple stems growing from the one rootstock.

This is why the oldest tree in the world is generally regarded as a single-stemmed bristlecone pine called Pinus longaeva.

This species can live to around 5,000 years and does well where most other plants cannot even grow in rocky, dry, high-altitude areas in the United States.

What's amazing is that scientists have not so far been able to show that getting older directly affects the health of such millennial trees, plant biologist Sergi Munne-Bosch from the University of Barcelona says.

It's because of this, some have suggested these trees are essentially immortal.

But in a recent article, Professor Munne-Bosch argues that it's likely even ancient trees could die from old age assuming something else doesn't kill them first.

He emphasises that there's a difference between ageing, which is about how long an organism has lived, and age-related deterioration, which is referred to as senescence.

"Just because we can't track senescence in long-lived trees doesn't mean they are immortal."

Professor Munne-Bosch points to recent research on centuries-old Ginkgo biloba trees that found no evidence of senescence.

The study was the first to look for evidence of age-related changes in cells of the cambium, a layer just beneath the bark that contains cells that can produce new tissue throughout the plant's life.

It confirmed the long-lived trees, which in this case were up to 667 years old, were just as healthy as younger ones says Professor Munne-Bosch.

"They grow very well, they produce seeds, they produce flowers, so they are healthy."

He points out that even though a 667-year-old tree seems old when compared to a human, it is relatively young for a ginkgo.

"This species can live for more than two millennia."

Professor Munne-Bosch argues that the ginkgo researchers' data shows that older trees had thinner vascular tissue and that this hints at possible age-related deterioration that would be more obvious in even older trees.

Yet despite this deterioration, he says these trees are more likely to die from insects, disease, fire, drought or loggers, than old age.

"For a species that can live for millennia, aging is not really a problem in evolutionary terms because they are much more likely to die of something else."

The problem is there are so few of these long-lived trees that it's hard to get the data to know for certain whether they can die of old age.

"We cannot prove it either way," Professor Munne-Bosch says, adding that age-related deterioration is likely to happen in these trees at such a different pace compared to in humans.

"For a Ginkgo biloba, six centuries is not as physiologically relevant as it is to us."

Brenda Casper, a professor of biology at the University of Pennsylvania says it's not clear that the changes found in the older Ginkgo biloba trees were necessarily detrimental to the tree.

But she agrees the low number of millennial trees makes it hard to study their longevity.

"It's difficult to find statistical evidence for senescence."

Even if there were enough trees, she says some of the age-related deterioration may be hard to detect, or we may not know what to look for.

"It's not just internal physiology per se but it's the interaction of the tree with its environment."

For example, she says it would be hard to measure whether age had made a tree more susceptible to disease, or less structurally sound so it's more likely to fall over in a windstorm.

Even if the jury is out on whether millennial trees are immortal, some experts say their longevity could be inspirational for medical research.

Professor Munne-Bosch says such trees can draw on a bag of tricks to help them "postpone death".

First is having a simple body plan with modular-like branches and roots. This means they can compartmentalise any damaged or dead roots or branches and work around them.

"They can lose part of leaves or roots and continue to be healthy..

And he says although 95 per cent of the trunk of a tree might be dead, the living cambium just beneath the bark is "one of the secrets of longevity" in trees.

Millennial trees have used the combination of these features to their best advantage and Professor Munne-Bosch says these tricks are providing a model for scientists researching the negative effects of ageing.

"Imagine if we could regenerate our lungs or circulatory system every year, we would be much healthier than we are."

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Professor of biomedical engineering at the University of New South Wales, Melissa Knothe Tate is one researcher who is inspired by millennial trees.

"They have units and if one unit breaks you can replace it with another unit."

Only a small percentage of an individual long-lived tree may be alive, but she argues it's all about survival of the cells that are able to regenerate the tree.

"Those that survive best, survive longest."

"Millennial trees are the best survivors because they've seen a lot."

While a tree and a human might seem worlds apart, Professor Knothe Tate sees the similarities, pointing to the role of stem cells in maintaining bones in humans.

She says cells add new layers to bone, like tree rings, to increase girth and when bone is injured, stem cells quickly help repair it.

"We're constantly renewing our bones and trees do something similar."

Professor Knothe Tate says she is using stem cells and new biomaterials that emulate tree cambium, to create replacement tissue in the lab, and has several patents for the work.

"I think about plants a lot when I'm up in the mountains and amongst the trees."

Professor Knothe Tate, who draws on her training in philosophy, biology and mechanical engineering for her work, sees other similarities that can inspire research.

For example, she likens the human brain to the network of roots and branches that helps a tree remain resilient if one part is damaged, another part can sometimes take up the slack.

"As parts of the brain are injured or die, it's remarkable what functionality we can retain,

"If we knew which of the brain's networks were essential for certain functions, we may be able to grow them."

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Professor Knothe Tate also set up a science education project for girls that explores the parallels between the biomechanics of trees and bones. It was inspired by her observation of how huge trees sway like a blade of grass in the wind.

She has high hopes for the potential of regenerative medicine research that draws on knowledge from other disciplines like plant biology to extend human life.

"We can then start to think about making ourselves immortal."

Plant biologist Professor Munne-Bosch is also enthusiastic.

"The future of medicine is very similar to what has evolved in millennial trees."

But while regenerating tissues will help humans live much longer, he doubts we will ever be immortal.

"It won't be forever, because we are more likely to die of something else, whether it be an accident or a pandemic."

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Are very long-lived trees immortal and what can they teach humans? - ABC News

For Australias balding community, letting your hair down is just an idiom.

But soon, it may be a reality.

In a breakthrough in the battle against baldness, researchers from the University of Pennsylvania have managed to grow skin that develops distinct layers, including hair follicles,from stem cells.

Scientists were already able to grow skin cells, but recreating the complex, multi-layered skin structure has been a major challenge.

As the largest human organ, the skin has multiple functions including temperature regulation and bodily fluid retention to the sensing of touch and pain that increases the difficulty of synthesising it, researchers say.

But over a four-to-five month period, researchers succeeded in growing complex skin cells and hair follicles, which were grafted onto mice.

More than half of the mice sprouted hair from the process.

Its a development that may also affect those with genetic skin disorders and cancers, as well as those with burns or wounds.

But those who are a little thin on the top shouldnt get excited too fast.

There are several major questions that remain before this approach can become a reality, researchers Leo Wang and George Cotsarelis say.

Several other aspects of the authors approach will also need to be optimised before it can move to the clinic.

The hairs that grew in the current study were small; in future, furtheroptimisation of culture conditions will be needed to form large scalp hairs.

However, the authors conclude: The work holds great promise of clinical translation we are confident that research will eventually see this promise realised.

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Eradicating balding a step closer with new procedure in the cross hairs - The New Daily

Coming Together to Solve COVID-19 Mysteries

As the COVID-19 pandemic began to be felt, scientists at Penn started work todevelop a vaccineandassess possible treatments. But the scope of COVID-19 studies at the University goes much broader. Scientists whose typical work finds them investigating autoimmune disease, influenza, HIV/AIDS, Ebola, cancer, hemophilia and more, are now applying their deep understanding of biology to confront a novel threat.

What Does SARS COVID-19 Do To Our Lungs? Another respiratory infection, influenza, has been a focus of research led by Andrew Vaughan, Penn Vet assistant professor of biomedical sciences. But Dr. Vaughan didnt hesitate to begin studies of the novel coronavirus once its eventual impact became apparent. Now, graduate students and research specialists in his labworking no more than two together at a time to maximize social distancingare conducting new experiments focused more specifically on the biology of SARS-CoV-2, alongside parallel efforts by Edward Morrissey from PSOM. Knowing that the ACE2 receptor on lung cells is the gateway for the virus into the human body, theyre genetically manipulating alveolar type-two lung cells, which are particularly essential for continuing oxygen exchange deep in the lungs, to alter or block ACE2 gene expression to try to prevent viral entry.

Why are Men Worse Off Than Women? In a separate project, Dr. Vaughan is partnering with Montserrat Anguera, Penn Vet associate professor of biomedical sciences, to explore a curious feature of COVID-19 disease: the fact that more men than women become severely ill and die. A number of hypotheses have been put forward to explain the disparity, but the two labs are investigating one particular possibility.

Dr. Anguera had posted something on Twitter saying that the ACE2 gene happens to be on the X chromosome, meaning that women have two copies of it, said Dr. Vaughan. I immediately texted her and said, I think theres something to that.

Hormone expression levels are another factor that may influence sex differences in disease. Together, Drs. Anguera and Vaughans groups are both studying ACE2 expression and exposing alveolar type-two cells to various hormones to see how expression of viral receptors, ACE2 and others, changes. Ultimately wed like to see if this changes susceptibility to infection, working withSusan Weissand others, said Dr. Vaughan.

Do Genetics Influence Susceptibility? Individual differences in how people respond to infection may be influenced by their unique genomic sequences. PIK Professor Sarah Tishkoff of PSOM and SAS is probing the rich sources of genomic data her group already had in hand to look for patterns that could explain differences in disease susceptibility. Using genomic data from 2,500 Africans collected for another project, Dr. Tishkoffs team is looking for patterns of genetic diversity. Early findings suggest that natural selection may have acted upon on a version of the ACE2 gene, making it more common in some African populations with high exposure to animal viruses.

She is also collaborating withAnurag Vermaand Giorgio Sirugo of Penn Medicine to analyze genetic variation in samples from thePenn Medicine Biobank, looking in particular at people of African descent.

How is the Immune System Reacting? The immune system is what eliminates the virus, saidE. John Wherry, chair of Systems Pharmacology and Translational Therapeutics at PSOM. The immune system is what we need to activate with a good vaccine. But also, especially in many respiratory infections, the immune system is what also causes damage. A healthy outcome means your immune system is striking a balance between killing off the virus and not doing so much damage that it kills you.

Dr. Wherry and Michael Betts, professor of microbiology, have embarked on a study to discern both the magnitude of patients immune responses as well as their flavor, that is, what components in the immune system are being activated by the coronavirus. They are doing so by working with clinicians at HUP and, soon, atPenn Presbyterian Medical Center, to collect blood samples from patients with severe and more mild infections, as well as patients who have recovered from illness, to profile their immune reactions. Variety across patients strongly suggests that the treatments that work for one patient may not for another, Drs. Wherry and Betts note. They are speaking daily with their colleagues on the front lines of COVID-19 care, relaying what theyre finding out in the lab.

The PSOMs Ronald Collman, professor of medicine, andFrederic Bushman, William Maul Measey Professor in Microbiology, have been devoting attention to how the community of bacteria, viruses, fungi and parasites that dwell in the respiratory tract affect health and disease risk. They are now addressing that question in the context of COVID-19. According to Dr. Collman, The microbiome can help set the tone for the immune response to infections, influencing whether a patient ends up with mild or severe disease. And second, the microbiome is where infectious agents that can cause infection can arise from. So if a patient dies of an eventual pneumonia, the pathogen that caused that pneumonia may have been part of that individuals respiratory tract microbiome.

Working with nurses at HUP to collect samples, Drs. Collman and Bushman are analyzing the microbiome of both the upper and lower portions of the respiratory tract of COVID-19 patients. Their labs are using these samples to identify the types and quantities of organisms that compose the microbiome to find patterns in how they correlate with disease.

What Drugs Might Make An Impact? Absent a vaccine, researchers are looking to existing drugssome already approved by the US FDA for other maladiesto help patients recover once infected. Throughout his career,Ronald Harty, Penn Vet professor of pathobiology and microbiology, has worked to develop antivirals for other infections, such as Ebola, Marburg and Lassa Fever.

Though many of the biological details of how SARS-CoV-2 interacts with the human body are distinct from the other diseases Dr. Harty has studied, his group noticed a similarity: A sequence hes targeted in other virusesa motif called PPxYis also present in the spike protein of SARS-CoV-2, which the coronavirus uses to enter cells.

This caught our eye, said Dr. Harty, and piqued our interest in the very intriguing possibility that this PPxY motif could play a role in the severity of this particular virus. He is testing antivirals he has helped identify that block the replication of Ebola, Marburg and other viruses to see if they make a dent on the activity of SARS-CoV-2. Those experiments will be done in collaboration with colleagues whose labs can work in BSL-III or -IV laboratories.

Also of interest is the speculation that the coronavirus might disrupt cell-cell junctions in the human body, making them more permeable for virus spread.

Another faculty member is assessing whether a drug developed for a very different conditionpulmonary arterial hypertension(PAH)could serve coronavirus patients. Henry Daniell, vice-chair and W.D. Miller Professor in Penn Dentals department of basic and translational sciences, shared news that a drug grown in a plant-based platform to boost levels of ACE2 and its protein product, angiotensin (1-7), was progressing to the clinic to treat PAH. Dr. Daniell is now working withKenneth Margulies, PSOM professor of medicine and physiology and research and fellowship director of the Heart Failure and Transplant Program, to explore whether this novel oral therapy can improve the clinical course of patients with symptomatic COVID-19 infection.

Reduced ACE2 expression has been linked to acute respiratory distress, severe lung injury, multi-organ failure and death, especially in older patients. The earlier preclinical studies in PAH animal models showed that orally delivered ACE2 made in plant cells accumulated ten times higher in the lungs than in the blood and safely treated PAH. Now, new clinical studies have been developed to explore whether oral supplementation of ACE2 and angiotensin-1-7 can help mitigate complications of COVID-19 disease. The fact that freeze-dried plant cells can be stored at room temperature for as long as a year and can be taken at home by COVID-19 patients make this novel approach an attractive potential option.

This trial has been given a high priority by the Penn Clinical Trial Working Group, said Dr. Daniell. Im pleased that this looks to be on the cusp of moving forward to help the growing number of COVID-19 patients.

As the coronavirus began to spread in the US, Joshua Plotkin, Walter H. and Leonore C. Annenberg Professor of the Natural Sciences, began to raise alarms about Philadelphias St. Patricks Day parade. His studies of the 1918 flu pandemic had explored disease incidence and spread, and it was hard to avoid noticingthe role of the Liberty Loan paradedown Broad Street in triggering a rampant spread of flu back then. Now, with work conducted with two graduate students and faculty member Simon Levin fromPrinceton University, Dr. Plotkin has mathematically sound advice for policymakers hoping to effectively stem the spread of a pandemic. In apreprint on arXiv.org, they share optimal, near-optimal, and robust strategies.

Their analysis makes the realistic assumption that policymakers can only enforce social distancing for a limited amount of time and aims to minimize the peak incidence of disease. The optimal strategy, they found, is to start by introducing moderate social distancing measures to keep the incidence rate the same for a period of time. This would mean that every person with COVID-19 would infect one additional person. Then the intervention should switch over to a full suppressionthe strongest possible quarantinefor the rest of the period. At the end of that period, all restrictions would be lifted.

This works because you dont want to fully suppress disease spread right off the bat, said Dr. Plotkin, because then at the end, after you remove restrictions, there will be a second peak that is just as large as the first. By employing a moderate suppression at the beginning, youre building up a population of people who are going to recover and become immune, without letting the epidemic get out of control.

Dr. Plotkin and colleagues are hoping to share the findings widely to help navigate a likely second wave of COVID-19.

Adapted from a story by Katie Baillie, Penn TodayVisithttps://tinyurl.com/pennandcovid for the full story.

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Coming Together to Solve COVID-19 Mysteries | University of Pennsylvania Almanac - UPENN Almanac

As an alternative to orthopedic surgery, patients traditionally seek treatments such as an injection of cartilage substitutes or steroids. Despite some short-term relief, steroids actually damage tissues over time and are not a viable long-term option.

Joint Osteoarthritis is the degeneration of the joint components, both cartilage and bone. Experts agree that stem cells may help in the repair of osteoarthritis in many ways, since they may act as anti-inflammatory mediators, or forming new cartilage or bone cells, by differentiation. Each individual patient will be evaluated to determine the potential success with stem cell therapy.

Patients coping with arthritis, sports injuries, tendon strains, sprained ligaments, muscle injuries and more, will be comforted to know that surgery is not the only option of treatment available to them. Faster healing as well as improved functionality both are possible with innovative, cutting- edge adult stem cell treatments.

There are breakthroughs in non-surgical treatments for people suffering from knee pain due to common injuries to the knee meniscus, ACL or MCL. If you are experiencing cartilage damage or degenerative conditions, such as osteoarthritis, traditional options for patients suffering from these conditions include

Now, there are new ways to aid in the destruction of cartilage in your knees. Results show alternatives to surgery and Stem Cell Therapy is being recommended by more scientists and doctors every week. Stem cell research offers unprecedented opportunities for developing new treatments for debilitating diseases for which there are few or no cures. Among the knee injuries and conditions that may be treated with stem cells include:

Osteoarthritis (OA) is a degenerative joint disease that can affect any joint in your body, including your hips. Over time, due to aging, trauma or other factors, the cartilage that cushions your joints starts to break down. Without cartilage, your joint bones rub together when you move. The bone-on-bone action creates pain, stiffness, and can limit your mobility. This is especially true with OA of the hip, as the hip contains large joints that carry your bodys weight with each step you take. Treatment options for hip arthritis range from lifestyle modifications to pain management, exercise programs, and even surgery.

Non-surgical stem cell injection procedures happen within a single day and may offer a viable alternative for those who are facing surgery or hip replacement. Patients are far less vulnerable to the serious risks associated with traumatic hip surgeries, such as infection and blood clots.

Our patients quickly return to normal activity following their procedure and are able to avoid the painful and lengthy rehabilitation periods that are required following hip surgery to help restore

A common sources of shoulder pain is arthritis: which is a degenerative process causing pain, swelling, stiffness, and disability. Minor shoulder issues, for example, sore muscles and a throbbing painfulness, are regular. Shoulder pain develops from ordinary wear and tear, overuse, or a damage.

At PA Stem Cell Centers, we are a leading non-surgical specialist for chronic shoulder pain and injuries from:

As ankle pain and ankle arthritis surgery alternatives, stem cell therapy may help alleviate the cause of pain with simple office injection procedure. Patients are encouraged to walk the same day, and most experience almost no down time after the procedure.

At PA Stem Cell Centers, we are a non-surgical specialists for chronic ankle pain and injuries from:

PA Stem Cell Treatment Centers offer non-surgical, stem cell treatments for patients who are suffering from wrist and hand pain or may be facing wrist or hand surgery due to ligament injury, tendonitis, bone injuries, arthritis, bursitis and other medical conditions.

If you have an injury or pain in your hand or wrist from ligament or tendon sprains or tear, or due to osteoarthritis, you may be a candidate for stem cell therapy. At PA Stem Cell Therapy, we are leading non-surgical specialist for chronic wrist and hand pain and injuries from:

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Orthopedics - Pennsylvania Stem Cell Center

Stem Cell Treatment in Philadelphia, PA

To treat joint and musculoskeletal system injuries, or if you suffer from chronic conditions affecting the joints or bones, there are options other than surgery to treat the issues. At World Wellness Health Institute, Dr. Daniel Lebowitz uses stem cell therapy on people living in and around Bala Cynwyd and Philadelphia, PA, who have chronic conditions and are in need of advanced treatment to heal injuries and relieve pain associated with injuries, arthritis, and other conditions.

Stem cell therapy is a cutting-edge treatment used in orthopedic injuries and other chronic conditions that affect the musculoskeletal system, such as arthritis and neck, back and joint pain. It is now a consideration for treatment instead of surgery. With stem cell therapy, many patients regain full function of the treated area without a lengthy recovery period, unlike with surgery. This type of stem cell therapy is FDA approved and takes stem cells from the patients own adipose tissue. This tissue (fat tissue) is rich in stem cells, primarily mesenchymalstem cells.

Stem cell injections are used primarily to relieve pain in the joints as they provide the following benefits:

With stem cell therapy, fat is harvested in a process called lipoaspiration. The targeted area is numbed with a local anesthetic, then a small needle just a tad larger than a hypodermic needle is injected into the skin to remove about 10 to 20ccs of adipose tissue (fat). Once the fat is removed, it is run through another process called sterile gravity method and combined with high-density PRP (platelet-rich plasma) and injected into the site where the pain occurs. Stem cells stimulate the healing process providing several functions. They can differentiate or even change into the type of cells needed, whether its a ligament, tendon, bone or cartilage, at the injection site to start healing. We prescribe oral anti-anxiety medicine and pain medicines that you can take prior to the procedure. If necessary, Dr. Lebowitz may use local anesthetic to numb the injection sites. You typically need only one treatment but, if necessary, a follow-up treatment may be performed several weeks later.

Much of the preparation for stem cell therapy involves determining if the patient is a good candidate for this type of treatment. It is necessary to stop taking any medications and/or supplements that may thin the blood at least one week prior to the treatment, as well as avoid smoking.

Stem cell therapy treatment is not a painful procedure, as oral pain relievers and local anesthetics are used to numb the treatment areas. It is okay to return to work immediately after the procedure, as well as participate in any activities. Most patients notice improvement after two weeks and continue to experience improvement over the next few months following the treatment.

Stem cell therapy is a relatively new procedure and varies in cost depending on the area to be treated, how many treatments may be required and if it is done at the same time another treatment is performed. We can discuss the cost with you during your consultation, in addition to going over our payment options. We do offerfinancingthrough CareCredit.

If you suffer from osteoarthritis or an injury to the knee, back, neck or other joint, stem cell therapy may be right for you. Stem cell therapy is an alternative to invasive surgery when the injured area is not fully collapsed.

During your consultation to determine if you are a candidate for stem cell therapy, it is necessary for Dr. Lebowitz to examine and evaluate the area of your pain, as well as determine the root cause of the pain. Additionally, he will go over your current health, medical history, and lifestyle in terms of diet, exercise, and more. If you have any questions, he answers them in detail so that you fully understand the treatment plan.

If you are experiencing pain in any joint or other part of the musculoskeletal system as a result of an injury or chronic health condition, stem cell therapy offered at World Wellness Health Institute may be the solution. Dr. Daniel Lebowitz offers several treatments for musculoskeletal therapy to residents in Bala Cynwyd, Philadelphia and the surrounding areas of Pennsylvania.Contact ustoday!*Individual results may vary

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