Category Archives: Minnesota Stem Cells

The immune system overreaction to COVID-19 has become a key target for therapeutic research, including a new trial at the University of Minnesota using stem cells to try to suppress the bodys response to infection and repair the damage it causes.

U researchers have been planning from the start to study the potential therapeutic benefits of mesenchymal stem cells (MSCs) against severe COVID-19.

Food and Drug Administration to test the stem cell therapy in patients who have already been hospitalized for COVID-19 and placed on ventilators due to respiratory distress.

The NK study is more preventive, enrolling patients who have not yet suffered respiratory distress during their COVID-19 hospitalizations but appear at risk.

A COVID-19 Treatment Guidelines team formed by the National Institutes of Health has reviewed evidence for using mesenchymal stem cells to treat this hyperimmune response but does not recommend them outside of clinical trials.

Mesenchymal stem cells are promising for COVID-19 because they gravitate toward the lung tissue that is inflamed by the immune response to the virus and because they target all types of cytokines, said Dr.

The stem cells seem to have a suppressive effect for only 48 hours, so the U trial will provide patients with three infusions during the critical week in which they first suffer respiratory distress.

The end-value of this stem cell therapy could depend on the development of other preventive therapies for COVID-19 or a vaccine, but Wagner said it could end up as a vital treatment option in this pandemic and for other causes of severe respiratory distress.

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University of Minnesota launches stem cell trial against ...

The immune system overreaction to COVID-19 has become a key target for therapeutic research, including a new trial at the University of Minnesota using stem cells to try to suppress the bodys response to infection and repair the damage it causes.

While COVID-19 patients can die from heart disease, stroke or blood clots, many die from respiratory failure caused by a cytokine storm, the release of immune-signaling proteins that can ultimately clog the lungs and cut off the oxygen supply to blood.

Sometimes its the lungs themselves and the cytokine storms, said Dr. David Ingbar, a critical care and pulmonary specialist leading the U trial. Sometimes its making people so weak and ill that they are set up for other complications.

Minnesota has totaled 1,685 COVID-19 deaths along with 62,993 infections with the coronavirus that causes the infectious disease.

The Minnesota Department of Health also reported that 308 people were hospitalized for COVID-19 on Thursday including 154 who needed intensive care due to breathing problems and other complications and that 5,742 people have been hospitalized since the pandemic arrived in the state six months ago.

U researchers have been planning from the start to study the potential therapeutic benefits of mesenchymal stem cells (MSCs) against severe COVID-19. The U pioneered the use of these cells which are produced in bone marrow to repair cartilage and bone in the body in the treatment of other severe immune-related diseases.

The U announced the trial Thursday following approval by the U.S. Food and Drug Administration to test the stem cell therapy in patients who have already been hospitalized for COVID-19 and placed on ventilators due to respiratory distress.

The first enrollee received an infusion Wednesday, though its unclear in the comparative blind trial whether that person received the stem cells or a non-medicating placebo.

The study is the second this month announced by the U to target the cytokine storm reaction. The other seeks to use a therapy derived from natural killer cells, the sentry dogs of the immune system that attack viruses while tailored antibody responses are developed.

The NK study is more preventive, enrolling patients who have not yet suffered respiratory distress during their COVID-19 hospitalizations but appear at risk.

While there are many types of cytokines, the commonality is that they are released as signals to the immune system of what to target and how forcefully to respond. The release of excessive cytokines can be toxic to the lungs on its own, but it also dilates the blood vessels, which leak fluid that can build up in the lungs and inhibit oxygen flow.

Many patients are full of virus but dont show severe symptoms until after the immune system response, said Dr. Frank Rhame, a virologist for Allina Health in Minneapolis. That really sharply illustrates that its the reaction, not the illness, that does this.

A COVID-19 Treatment Guidelines team formed by the National Institutes of Health has reviewed evidence for using mesenchymal stem cells to treat this hyperimmune response but does not recommend them outside of clinical trials.

Its very much not ready for clinical implementation and clinical use, said Dr. Jason Baker, a Hennepin Health doctor who is part of the NIH review team. There is potential, but it very much needs to be proven.

COVID-19 research so far has shown that the drug remdesivir has antiviral properties that can prevent severe respiratory symptoms if given early in hospitalizations, and that the steroid dexamethasone may fight inflammation in severe cases and reduce the risk of death.

The U was involved in the national remdesivir trial and also conducted trials that found that hydroxychloroquine did not prevent the onset of symptoms in people exposed to the coronavirus. The U also is continuing a COVID-19 trial of losartan, a drug usually administered to treat high blood pressure.

One of the Us first successes with mesenchymal stem cells was in the treatment of graft-versus-host disease, a condition in which the bodys immune system rejects transplanted organs.

Mesenchymal stem cells are promising for COVID-19 because they gravitate toward the lung tissue that is inflamed by the immune response to the virus and because they target all types of cytokines, said Dr. John Wagner, director of the Us Institute for Cell, Gene and Immunotherapy.

The reason we believe this might be a better approach to inhibiting the cytokine storm is because it tackles all of them simultaneously, he said.

The U had been an early user of a cancer drug, tocilizumab, as an immune-fighting therapy including in the treatment of a young Ironman athlete in March who was Minnesotas first COVID-19 case to be placed on a ventilator and into a medically induced coma. That drug targets a single cytokine, IL-6, that appears to play a key role in the immune response to COVID-19.

Small studies out of China and Italy raised the prospect of some benefit in the use of MSCs against COVID-19, but they enrolled few patients and had no placebo comparison.

The stem cells seem to have a suppressive effect for only 48 hours, so the U trial will provide patients with three infusions during the critical week in which they first suffer respiratory distress.

Timing will be crucial, because the deterioration can be rapid, Ingbar said. Consent will often have to come via video from the patients designated medical decisionmakers, because patients will be on ventilators and unable to give the OK on their own.

The end-value of this stem cell therapy could depend on the development of other preventive therapies for COVID-19 or a vaccine, but Wagner said it could end up as a vital treatment option in this pandemic and for other causes of severe respiratory distress.

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University of Minnesota launches stem cell trial against severe COVID-19 - Minneapolis Star Tribune

When Ralph Fisher, a Texas cattle rancher, set eyes on one of the worlds first cloned calves in August 1999, he didnt care what the scientists said: He knew it was his old Brahman bull, Chance, born again. About a year earlier, veterinarians at Texas A&M extracted DNA from one of Chances moles and used the sample to create a genetic double. Chance didnt live to meet his second self, but when the calf was born, Fisher christened him Second Chance, convinced he was the same animal.

Scientists cautioned Fisher that clones are more like twins than carbon copies: The two may act or even look different from one another. But as far as Fisher was concerned, Second Chance was Chance. Not only did they look identical from a certain distance, they behaved the same way as well. They ate with the same odd mannerisms; laid in the same spot in the yard. But in 2003, Second Chance attacked Fisher and tried to gore him with his horns. About 18 months later, the bull tossed Fisher into the air like an inconvenience and rammed him into the fence. Despite 80 stitches and a torn scrotum, Fisher resisted the idea that Second Chance was unlike his tame namesake, telling the radio program This American Life that I forgive him, you know?

In the two decades since Second Chance marked a genetic engineering milestone, cattle have secured a place on the front lines of biotechnology research. Today, scientists around the world are using cutting-edge technologies, from subcutaneous biosensors to specialized food supplements, in an effort to improve safety and efficiency within the $385 billion global cattle meat industry. Beyond boosting profits, their efforts are driven by an imminent climate crisis, in which cattle play a significant role, and growing concern for livestock welfare among consumers.

Gene editing stands out as the most revolutionary of these technologies. Although gene-edited cattle have yet to be granted approval for human consumption, researchers say tools like Crispr-Cas9 could let them improve on conventional breeding practices and create cows that are healthier, meatier, and less detrimental to the environment. Cows are also being given genes from the human immune system to create antibodies in the fight against Covid-19. (The genes of non-bovine livestock such as pigs and goats, meanwhile, have been hacked to grow transplantable human organs and produce cancer drugs in their milk.)

But some experts worry biotech cattle may never make it out of the barn. For one thing, theres the optics issue: Gene editing tends to grab headlines for its role in controversial research and biotech blunders. Crispr-Cas9 is often celebrated for its potential to alter the blueprint of life, but that enormous promise can become a liability in the hands of rogue and unscrupulous researchers, tempting regulatory agencies to toughen restrictions on the technologys use. And its unclear how eager the public will be to buy beef from gene-edited animals. So the question isnt just if the technology will work in developing supercharged cattle, but whether consumers and regulators will support it.

Cattle are catalysts for climate change. Livestock account for an estimated 14.5 percent of greenhouse gas emissions from human activities, of which cattle are responsible for about two thirds, according to the United Nations Food and Agriculture Organization (FAO). One simple way to address the issue is to eat less meat. But meat consumption is expected to increase along with global population and average income. A 2012 report by the FAO projected that meat production will increase by 76 percent by 2050, as beef consumption increases by 1.2 percent annually. And the United States is projected to set a record for beef production in 2021, according to the Department of Agriculture.

For Alison Van Eenennaam, an animal geneticist at the University of California, Davis, part of the answer is creating more efficient cattle that rely on fewer resources. According to Van Eenennaam, the number of dairy cows in the United States decreased from around 25 million in the 1940s to around 9 million in 2007, while milk production has increased by nearly 60 percent. Van Eenennaam credits this boost in productivity to conventional selective breeding.

You dont need to be a rocket scientist or even a mathematician to figure out that the environmental footprint or the greenhouse gases associated with a glass of milk today is about one-third of that associated with a glass of milk in the 1940s, she says. Anything you can do to accelerate the rate of conventional breeding is going to reduce the environmental footprint of a glass of milk or a pound of meat.

Modern gene-editing tools may fuel that acceleration. By making precise cuts to DNA, geneticists insert or remove naturally occurring genes associated with specific traits. Some experts insist that gene editing has the potential to spark a new food revolution.

Jon Oatley, a reproductive biologist at Washington State University, wants to use Crispr-Cas9 to fine tune the genetic code of rugged, disease-resistant, and heat-tolerant bulls that have been bred to thrive on the open range. By disabling a gene called NANOS2, he says he aims to eliminate the capacity for a bull to make his own sperm, turning the recipient into a surrogate for sperm-producing stem cells from more productive prized stock. These surrogate sires, equipped with sperm from prize bulls, would then be released into range herds that are often genetically isolated and difficult to access, and the premium genes would then be transmitted to their offspring.

Furthermore, surrogate sires would enable ranchers to introduce desired traits without having to wrangle their herd into one place for artificial insemination, says Oatley. He envisions the gene-edited bulls serving herds in tropical regions like Brazil, the worlds largest beef exporter and home to around 200 million of the approximately 1.5 billion head of cattle on Earth.

Brazils herds are dominated by Nelore, a hardy breed that lacks the carcass and meat quality of breeds like Angus but can withstand high heat and humidity. Put an Angus bull on a tropical pasture and hes probably going to last maybe a month before he succumbs to the environment, says Oatley, while a Nelore bull carrying Angus sperm would have no problem with the climate.

The goal, according to Oatley, is to introduce genes from beefier bulls into these less efficient herds, increasing their productivity and decreasing their overall impact on the environment. We have shrinking resources, he says, and need new, innovative strategies for making those limited resources last.

Oatley has demonstrated his technique in mice but faces challenges with livestock. For starters, disabling NANOS2 does not definitively prevent the surrogate bull from producing some of its own sperm. And while Oatley has shown he can transplant sperm-producing cells into surrogate livestock, researchers have not yet published evidence showing that the surrogates produce enough quality sperm to support natural fertilization. How many cells will you need to make this bull actually fertile? asks Ina Dobrinski, a reproductive biologist at the University of Calgary who helped pioneer germ cell transplantation in large animals.

But Oatleys greatest challenge may be one shared with others in the bioengineered cattle industry: overcoming regulatory restrictions and societal suspicion. Surrogate sires would be classified as gene-edited animals by the Food and Drug Administration, meaning theyd face a rigorous approval process before their offspring could be sold for human consumption. But Oatley maintains that if his method is successful, the sperm itself would not be gene-edited, nor would the resulting offspring. The only gene-edited specimens would be the surrogate sires, which act like vessels in which the elite sperm travel.

Even so, says Dobrinski, Thats a very detailed difference and Im not sure how that will work with regulatory and consumer acceptance.

In fact, American attitudes towards gene editing have been generally positive when the modification is in the interest of animal welfare. Many dairy farmers prefer hornless cowshorns can inflict damage when wielded by 1,500-pound animalsso they often burn them off in a painful process using corrosive chemicals and scalding irons. In a study published last year in the journal PLOS One, researchers found that most Americans are willing to consume food products from cows genetically modified to be hornless.

Still, experts say several high-profile gene-editing failures in livestock and humans in recent years may lead consumers to consider new biotechnologies to be dangerous and unwieldy.

In 2014, a Minnesota startup called Recombinetics, a company with which Van Eenennaams lab has collaborated, created a pair of cross-bred Holstein bulls using the gene-editing tool TALENs, a precursor to Crispr-Cas9, making cuts to the bovine DNA and altering the genes to prevent the bulls from growing horns. Holstein cattle, which almost always carry horned genes, are highly productive dairy cows, so using conventional breeding to introduce hornless genes from less productive breeds can compromise the Holsteins productivity. Gene editing offered a chance to introduce only the genes Recombinetics wanted. Their hope was to use this experiment to prove that milk from the bulls female progeny was nutritionally equivalent to milk from non-edited stock. Such results could inform future efforts to make Holsteins hornless but no less productive.

The experiment seemed to work. In 2015, Buri and Spotigy were born. Over the next few years, the breakthrough received widespread media coverage, and when Buris hornless descendant graced the cover of Wired magazine in April 2019, it did so as the ostensible face of the livestock industrys future.

But early last year, a bioinformatician at the FDA ran a test on Buris genome and discovered an unexpected sliver of genetic code that didnt belong. Traces of bacterial DNA called a plasmid, which Recombinetics used to edit the bulls genome, had stayed behind in the editing process, carrying genes linked to antibiotic resistance in bacteria. After the agency published its findings, the media reaction was swift and fierce: FDA finds a surprise in gene-edited cattle: antibiotic-resistant, non-bovine DNA, read one headline. Part cow, part bacterium? read another.

Recombinetics has since insisted that the leftover plasmid DNA was likely harmless and stressed that this sort of genetic slipup is not uncommon.

Is there any risk with the plasmid? I would say theres none, says Tad Sonstegard, president and CEO of Acceligen, a Recombinetics subsidiary. We eat plasmids all the time, and were filled with microorganisms in our body that have plasmids. In hindsight, Sonstegard says his teams only mistake was not properly screening for the plasmid to begin with.

While the presence of antibiotic-resistant plasmid genes in beef probably does not pose a direct threat to consumers, according to Jennifer Kuzma, a professor of science and technology policy and co-director of the Genetic Engineering and Society Center at North Carolina State University, it does raise the possible risk of introducing antibiotic-resistant genes into the microflora of peoples digestive systems. Although unlikely, organisms in the gut could integrate those genes into their own DNA and, as a result, proliferate antibiotic resistance, making it more difficult to fight off bacterial diseases.

The lesson that I think is learned there is that science is never 100 percent certain, and that when youre doing a risk assessment, having some humility in your technology product is important, because you never know what youre going to discover further down the road, she says. In the case of Recombinetics. I dont think there was any ill intent on the part of the researchers, but sometimes being very optimistic about your technology and enthusiastic about it causes you to have blinders on when it comes to risk assessment.

The FDA eventually clarified its results, insisting that the study was meant only to publicize the presence of the plasmid, not to suggest the bacterial DNA was necessarily dangerous. Nonetheless, the damage was done. As a result of the blunder,a plan was quashed forRecombinetics to raise an experimental herd in Brazil.

Backlash to the FDA study exposed a fundamental disagreement between the agency and livestock biotechnologists. Scientists like Van Eenennaam, who in 2017 received a $500,000 grant from the Department of Agriculture to study Buris progeny, disagree with the FDAs strict regulatory approach to gene-edited animals. Typical GMOs are transgenic, meaning they have genes from multiple different species, but modern gene-editing techniques allow scientists to stay roughly within the confines of conventional breeding, adding and removing traits that naturally occur within the species. That said, gene editing is not yet free from errors and sometimes intended changes result in unintended alterations, notes Heather Lombardi, division director of animal bioengineering and cellular therapies at the FDAs Center for Veterinary Medicine. For that reason, the FDA remains cautious.

Theres a lot out there that I think is still unknown in terms of unintended consequences associated with using genome-editing technology, says Lombardi. Were just trying to get an understanding of what the potential impact is, if any, on safety.

Bhanu Telugu, an animal scientist at the University of Maryland and president and chief science officer at the agriculture technology startup RenOVAte Biosciences, worries that biotech companies will migrate their experiments to countries with looser regulatory environments. Perhaps more pressingly, he says strict regulation requiring long and expensive approval processes may incentivize these companies to work only on traits that are most profitable, rather than those that may have the greatest benefit for livestock and society, such as animal well-being and the environment.

What company would be willing to spend $20 million on potentially alleviating heat stress at this point? he asks.

On a windy winter afternoon, Raluca Mateescu leaned against a fence post at the University of Floridas Beef Teaching Unit while a Brahman heifer sniffed inquisitively at the air and reached out its tongue in search of unseen food. Since 2017, Mateescu, an animal geneticist at the university, has been part of a team studying heat and humidity tolerance in breeds like Brahman and Brangus (a mix between Brahman and Angus cattle). Her aim is to identify the genetic markers that contribute to a breeds climate resilience, markers that might lead to more precise breeding and gene-editing practices.

In the South, Mateescu says, heat and humidity are a major problem. That poses a stress to the animals because theyre selected for intense productionto produce milk or grow fast and produce a lot of muscle and fat.

Like Nelore cattle in South America, Brahman are well-suited for tropical and subtropical climates, but their high tolerance for heat and humidity comes at the cost of lower meat quality than other breeds. Mateescu and her team have examined skin biopsies and found that relatively large sweat glands allow Brahman to better regulate their internal body temperature. With funding from the USDAs National Institute of Food and Agriculture, the researchers now plan to identify specific genetic markers that correlate with tolerance to tropical conditions.

If were selecting for animals that produce more without having a way to cool off, were going to run into trouble, she says.

There are other avenues in biotechnology beyond gene editing that may help reduce the cattle industrys footprint. Although still early in their development, lab-cultured meats may someday undermine todays beef producers by offering consumers an affordable alternative to the conventionally grown product, without the animal welfare and environmental concerns that arise from eating beef harvested from a carcass.

Other biotech techniques hope to improve the beef industry without displacing it. In Switzerland, scientists at a startup called Mootral are experimenting with a garlic-based food supplement designed to alter the bovine digestive makeup to reduce the amount of methane they emit. Studies have shown the product to reduce methane emissions by about 20 percent in meat cattle, according to the New York Times.

In order to adhere to the Paris climate agreement, Mootrals owner, Thomas Hafner, believes demand will grow as governments require methane reductions from their livestock producers. We are working from the assumption that down the line every cow will be regulated to be on a methane reducer, he told the New York Times.

Meanwhile, a farm science research institute in New Zealand, AgResearch, hopes to target methane production at its source by eliminating methanogens, the microbes thought to be responsible for producing the greenhouse gas in ruminants. The AgResearch team is attempting to develop a vaccine to alter the cattle guts microbial composition, according to the BBC.

Genomic testing may also allow cattle producers to see what genes calves carry before theyre born, according to Mateescu, enabling producers to make smarter breeding decisions and select for the most desirable traits, whether it be heat tolerance, disease resistance, or carcass weight.

Despite all these efforts, questions remain as to whether biotech can ever dramatically reduce the industrys emissions or afford humane treatment to captive animals in resource-intensive operations. To many of the industrys critics, including environmental and animal rights activists, the very nature of the practice of rearing livestock for human consumption erodes the noble goal of sustainable food production. Rather than revamp the industry, these critics suggest alternatives such as meat-free diets to fulfill our need for protein. Indeed, data suggests many young consumers are already incorporating plant-based meats into their meals.

Ultimately, though, climate change may be the most pressing issue facing the cattle industry, according to Telugu of the University of Maryland, which received a grant from the Bill and Melinda Gates Foundation to improve productivity and adaptability in African cattle. We cannot breed our way out of this, he says.

This article was originally published on Undark. Read the original article.

Image Credit: RitaE from Pixabay

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Biotechnology Could Change the Cattle Industry. Will It Succeed? - Singularity Hub

SAN DIEGO, April 02, 2020 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, today announced that the first patient has been treated in the Companys first-in-human Phase 1 clinical trial evaluating FT596, the first cell therapy product candidate engineered with three active anti-tumor modalities, in patients with B-cell malignancies and chronic lymphocytic leukemia. FT596 is an off-the-shelf chimeric antigen receptor (CAR) natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a proprietary CD19-targeting CAR, a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, and a unique interleukin-15 receptor fusion (IL-15RF). The hnCD16 Fc receptor enables coincident targeting of additional tumor-associated antigens expressed on cancer cells to overcome antigen escape, and IL-15RF is a potent cytokine complex that promotes survival, proliferation and trans-activation of NK cells and CD8 T cells without the need for systemic cytokine support.

We are pleased to have worked with the Masonic Cancer Center, University of Minnesota to treat the first patient with FT596, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. The COVID-19 pandemic presents unprecedented challenges for clinical trial conduct worldwide, and we anticipate there will be delays across our studies. We are committed to the health and safety of our employees and partners, and have implemented a remote work program to the greatest extent possible while continuing certain activities that can only be completed on-site. We are also working closely with our clinical sites and principal investigators so that we are well positioned to accelerate clinical trial execution when pressures on the health system ease.

In response to the global COVID-19 pandemic, the Company is providing a business update on the conduct of its operations.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

About FT596FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon dual receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in an open-label Phase 1 clinical trial as a monotherapy, and in combination with rituximab, for the treatment of advanced B-cell lymphoma and in combination with obinutuzumab for the treatment of chronic lymphocytic leukemia (NCT04245722).

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About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Companys immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the therapeutic and market potential of the Companys product candidates and iPSC product platform, the advancement of and plans related to the Companys product candidates, clinical studies and preclinical research and development programs, the Companys progress, plans and timelines for conduct of the Companys Phase 1 clinical trials of its product candidates, plans and timelines for submitting INDs for its product candidates, and the Companys plans and expectations in light of and in response to the COVID-19 pandemic and its impacts on the healthcare system and the Companys business. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the disruptions to the Companys business and the healthcare system as a result of the COVID-19 pandemic may be more severe than are anticipated, the risk that results observed in prior studies of the Companys product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Companys product candidates or in the initiation of, or enrollment of patients in, any clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including disruptions to the Companys or third parties operations as a result of the COVID-19 pandemic, requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties or delays in patient enrollment in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that the Companys expenditures may exceed current expectations for a variety of reasons. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

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Fate Therapeutics Announces First Patient Treated in First-in-human Clinical Trial of FT596 and Provides Corporate Update - Yahoo Finance

`It wasnt long after the events of Sept. 11, 2001, that cops, firefighters, first responders and volunteers from across the country and the world were lauded as heroes and temporarily replaced celebrities as the guest stars on talk shows.

The acknowledgment lasted for a while before actors hawking movies and pundits plugging books became the norm again.

As for the most affected first responders those who risked their health and spent weeks sifting through the rubble of the World Trade Center for remains and evidence too many succumbed to cancer and respiratory illnesses that took their lives or permanently scarred them physically and emotionally.

Hopefully, the workers now on the front line of the coronavirus crisis will receive a far more enduring tribute and recognition. Quite a number of them have been infected and some have died while trying to treat patients in their care. They range from the Chinese physician who sounded the first warning of this novel virus to doctors and nurses and others here who have come down with the deadly infection. Add the Italian pastor who died after willingly giving up his ventilator for a younger COVID-19 patient.

I know of this front-line work first hand.

Nine years ago this week on April Fools Day I got the news that I had multiple myeloma, a cancer of the plasma cells. More than 32,000 American adults are diagnosed annually with the incurable disease; more than 12,000 die of complications from it. I was informed I had the worst stage of it. Close to 80 percent of my plasma cells were cancerous. Tests also discovered fractured vertebrae and weakened bones byproducts of the cancer. The average survival rate for Stage III folks like me is 29 months, though treatment protocols have improved over the years.

I went through a year of chemo and a ruptured appendix during aggressive treatment that left me with an ugly but necessary vertical scar that wiped out my belly button. Throw in two autologous stem cell transplants as well as several bouts of pneumonia and other weird respiratory emergencies throughout the years.

Nine years later Im still above ground. I can still work, hoop and salsa, and I checked off some wishes Iike swimming with dolphins and experiencing the worlds second longest zipline. My only treatment since late 2012 is ingesting a daily Revlimid pill that doctors believe is keeping my cancer at below microscopic levels. My gut tells me it might also be the occasional Reeses Pieces, though I place my trust in the medical and scientific communitys assessment.

But Im blessed, thanks to my caretaker wife, the support from my family and friends, and the incredible knowledge and care I was given by those front-line health care workers who were with me step by step. Many are now dealing with the COVID-19 outbreak as well as the normal workload.

They include Dr. Mark Wilkowske, chief of oncology at the Frauenshuh Cancer Center in St. Louis Park, and Drs. Daniel Weisdorf, Philip McGlave and the team at the University of Minnesota Bone Marrow Transplant Program.

But I also am in debt to the long line of physicians, nurses and support staff who have helped me and many others recover from serious illnesses and other medical challenges throughout the years. We now see them profiled on TV sacrificing their own health, rightly pointing out the lack of official preparedness, and working double shifts while juggling family and emotional needs.

I have nothing against well-deserving celebrities. Whether they are musicians, actors or athletes, many have also stepped to the plate to entertain from home, donate to relief efforts or share words of support and solace through social media and other venues. But so have ordinary folks from all corners of the nation.

Maybe, when we do get back to normal, if we ever do, lets not forget what these health care folks and support staff are doing now, day in and day out. I know I wont.

Lets make that gratitude and star treatment last longer than it did 19 years ago.

Excerpt from:
A word for those risking their lives amid the coronavirus crisis: Thanks - TwinCities.com-Pioneer Press

Comparing between SARS, MERS and 2019-nCOv

The Wuhan coronavirus or novel 2019 nCoV, has spread like a wildfire across China and reached the shores of 22 countries as of now. In a bid to stem the spread of the disease, countries have resorted to various preventive and arresting measures. Many laboratories are in the process of formulating a vaccine. However, combating this new pathogen is proving to be a global challenge.

A new study by researchers from the University of Minnesota suggests that understanding the Severe acute respiratory syndrome virus (SARS) or SARS-CoV, which caused global panic in 2002-2003 may help combat the new coronavirus.

After a structural study that lasted for ten years, the researchers have been able to demonstrate the manner of interaction between the SARS-CoV and animals, and human hosts that lead to infection in them. The scientists suggest that the mechanism of infection of the Wuhan coronavirus exhibits similarities to the SARS-CoV, which also is a coronavirus.

Using the data and information acquired from multiple strains of SARS-CoV from diverse hosts from different years, and studying the angiotensin-converting enzyme-2 (ACE2) receptors from various species of host animals, the scientists modelled predictions for the Wuhan coronavirus. Normally, the enzyme is associated with the regulation of cardiac functions. However, both these viruses have been found to gain entry into healthy cells by using ACE2.

"Our structural analyses confidently predict that the Wuhan coronavirus uses ACE2 as its host receptor," the researchers wrote in the study. They state that various other structural details of the new coronavirus are consistent with the ability of the SARS-CoV to recognise the ACE2 receptors to infect the cells, playing a determining role in transmission from hosts to human beings, and human to human.

The researchers also stressed that a single mutation has the ability to increase the potency with which the virus can infect humans. "Alarmingly, our data predict that a single mutation [at a specific spot in the genome] could significantly enhance [the Wuhan coronavirus's] ability to bind with human ACE2," they stated in the study.

It is because of this danger that the evolution of the Wuhan virus among patients must be monitored closely to spot novel mutations in its genomes, the scientists add. This continuous examination may help predict the possibility of an outbreak that could be far more serious than the ones being witnessed the authors stress.

"One of the long -term goals of our previous structural studies on SARS -CoV was to build an atomic -level iterative framework of virus-receptor interactions that facilitate epidemic surveillance, predict species-specific receptor usage and identify potential animal hosts and likely animal models of human diseases," highlighted the authors.

They conclude that this study provides translational and public health research communities with a reiterative framework that may help provide predictive insights enabling the better understanding and counter of the novel 2019 -nCoV.

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Coronavirus is similar to SARS and causes infection through a heart regulating enzyme: Study - International Business Times, Singapore Edition

What happened

Shares of Sangamo Therapeutics (NASDAQ:SGMO) were sinking 11.7% lower as of 3:28 p.m. EST on Tuesday. This marked the second consecutive day of double-digit-percentage declines for the biotech stock after Sangamo announced preliminary results on Monday from a phase 1/2 clinical study evaluating experimental gene-editing therapy ST-400 in treating rare blood disease transfusion-dependent beta thalassemia (TDT).

Those preliminary results were for the first three patients in Sangamo's Thales clinical trial targeting beta thalassemia. The good news was that all three patients receiving ST-400 quickly experienced reconstitution of their hematopoietic stem cells after gene editing as well as demonstrating neutrophil engraftment -- the first day where the patients' neutrophil counts were at least 500 cells per microliter for three consecutive days.

Image source: Getty Images.

The not-so-good news related to the adverse effects experienced by the patients. One patient experienced a serious adverse event with hypersensitivity during the ST-400 infusion, although the issue resolved by the end of the infusion. Also, another patient's fetal hemoglobin levels increased by less than 1 gram per deciliter through week 26 of the study. The goal of ST-400 is to boost fetal hemoglobin levels enough to minimize the negative effects of beta thalassemia.

University of Minnesota Associate Professor Angela Smith, a principal investigator of the Thales study, noted that "the full effects of the treatment may take as long as 12 to 18 months or more to manifest." She added, "Longer-term follow-up, including from additional patients, will be necessary to understand the safety profile and potential clinical benefit of ST-400 in beta-thalassemia."

Adrian Woolfson, Sangamo's head of research and development, stated, "Our understanding of ST-400 will continue to evolve as we follow the progress of these and additional patients in the coming year, and those dosed in Sanofi's BIVV003 clinical trial, which is evaluating the same gene-editing approach in sickle cell disease."

This cautious language from both Smith and Woolfson underscores the tentative nature of the preliminary results.

Investors will have to wait a while to learn just how much promise ST-400 holds. Sangamo expects to announce additional study results late next year after enrollment in the Thales study is completed and after all six patients in the study have been observed for longer periods.

Sangamo's last week or so has demonstrated the volatility associated with biotech stocks, especially those with no approved drugs on the market. Sangamo jumped last week on positive results from another study (of hemophilia gene therapy SB-525) but gave up those gains and then some on the news for ST-400.

Read more from the original source:
Why Sangamo Therapeutics Stock Sank Today - The Motley Fool

U.S. Sen. John Hoeven (R-ND) on Sept. 18 introduced legislation to direct the U.S. Secretary of Veterans Affairs to furnish hyperbaric oxygen therapy to military veterans with traumatic brain injury (TBI) or post-traumatic stress disorder (PTSD).

Sen. Hoeven sponsored the TBI and PTSD Treatment Act, S. 2504, with bill cosponsor U.S. Sen. Kevin Cramer (R-ND) to provide veterans with hyperbaric oxygen therapy (HBOT), which involves breathing pure oxygen in a pressurized room or tube, according to the Mayo Clinic.

Our veterans deserve access to the best possible health care, and that includes alternative options like HBOT when traditional therapies arent delivering the outcomes our veterans need, Sen. Hoeven said.

HBOT is a well-established treatment for several conditions, the Mayo Clinic says, which noted that in a hyperbaric oxygen therapy chamber, the air pressure is increased to three times higher than normal air pressure so that a persons lungs can gather more oxygen, helping to fight bacteria and stimulate the release of substances called growth factors and stem cells, which promote healing.

The legislation would build on the VAs clinical demonstration program for HBOT, which earlier this month was expanded to the Fargo VA Health Care System in Sen. Hoevens home state. The local VA is the fifth location to be added to the HBOT program, joining VA systems in California, Florida, Oklahoma and Texas.

We worked for more than a year to bring HBOT access to veterans in North Dakota and Minnesota under the VAs clinical demonstration program, said Sen. Hoeven. With that program now under way, we are continuing to move the ball forward by advancing this legislation.

The bill has been referred to the U.S. Senate Veterans Affairs Committee for consideration.

Read more here:
Hoeven's bill supports alternative therapy for veterans with PTSD, traumatic brain injury - Ripon Advance

Last fall doctors at the University of Minnesota did a bone marrow transplant on a 2-year-old boy in a risky attempt to treat his devastating genetic skin disease with stem cells. Until then, the technique had only been used in mice.

It worked.

The boy's doctors said Monday they think they have found a cure for the painful disease that, though rare, causes the skin to fall off at the slightest touch and inevitably leads to cancer. Most children who have it do not survive to adulthood.

"Maybe we can take one more disorder off the incurable list," said Dr. John Wagner, a bone marrow specialist and stem cell researcher at the university. He agreed to treat Nate Liao after his mother begged Wagner to try using stem cells as therapy.

"It's not often that it feels like you hit a home run in medical research, but this one feels like it," Wagner said.

It is the first time a bone marrow transplant has been known to effectively treat something other than disorders of the bone marrow or blood, and it may prove useful for a number of both genetic and non-genetic skin disorders, Wagner said.

Nate,who had never been able to eat normal food, is demanding pork chops and Doritos.

On Friday his older brother Jake, who has the same genetic disease, was the second to receive a bone marrow transplant. Later this week a 9-month-old baby from California will be the third in a clinical research trial that will include 30 patients.

Wagner said that as word of the treatment has spread, families from around the world who are affected by the disease are asking him to include their children in the trial.

"I hope that when someone has a baby like this they will see our story and know it doesn't have to be that way," said Theresa Liao, Nate's mother, 37, who lives in Clarksburg, N.J.

The Liao boys have a disease called recessive dystrophic epidermolysis bullosa (RDEB). They were born without the ability to make a protein the body needs to form one of the collagens that hold the layers of skin together. It is rare, occurring in 10 out of every million people. There are other forms of the disease that are not as severe.

The slightest bump or scrape creates huge blisters on the skin that then sloughs off. It also affects the lining of the mouth, esophagus and intestinal tract, making it impossible for children to eat normally. Nate could only eat pureed food, his mother said. There is no treatment, only a constant need for bandages to hold potentially fatal complications at bay.

A mother's quest

Liao met Wagner when he was in New York to give a speech several years ago, and she challenged him to find a way to save her son, Jake, who was born with the disease. Later, he also met Angela Christiano, an expert on genetic skin disorders from Columbia University, and she suggested he could test stem cells by using mice genetically engineered to carry the disease.

Researchers at the university, which specializes in adult stem cells, began experimenting with a variety of stem cells found in bone marrow and blood from umbilical cords. Dr. Jakub Tolar, a blood specialist at the university, said he tried 10 to 15 different classes of cells in the genetically engineered mice in the hopes that one would provide the missing protein.

Finally, one did. Two years ago, Liao received the news that they had found something that might work when she was two weeks away from giving birth to Nate. She already knew he would be the second of her four children to carry the disease.

Tolar and Wagner said they are still not sure exactly which type of cell is the one that fixed the defect in mice. But they also knew it didn't matter. The boy would get the cells he needed in a full transplant using cord blood and bone marrow.

Nate was the first of her two sick children to get a transplant because he was a perfect match to another brother who does not have the disease. The transplant took place last October. Gradually his mother began to notice a difference in his skin.

"He looked thin-skinned and pale. That gradually started to change," Liao said. "My family, we looked at each other and said, 'Do you see this? It's not just me, right?'"

Tests showed that he was developing the missing collagen in his skin and in his intestinal tract. The doctors said that they think that the key stem cells somehow find their way from the bone marrow to the skin when they detect a signal from damaged skin cells. Somehow the stem cells sense what protein is missing and start making it. "We don't know what the cell is or what the signal is, but when it gets there we know what it does," Christiano said.

It's likely, Tolar said, that more than one type of cell is needed. "You need a main population, but also a helping population and together they synergize," he said.

Wagner says he thinks that both brothers will develop enough collagen to have healthy skin and digestive tracts.

Liao is now nursing Jake, 5, through the trauma of a bone marrow transplant. She says she is exhausted and stunned by Minnesota's weather -- the bitter winter and now a seemingly incessant stream of tornados and thunderstorms.

But soon she expects to be as happy as it's possible for a mother to be.

"By the end of year, do I think we will be looking at the best Christmas we could ever have? Yes. I do," she said.

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Stem-cell treatment gives two brothers a future ...

Diabetes

Diabetes has been diagnosed in about 11 million people in the United States. People with diabetes do not properly produce insulin, which is necessary to regulate sugars and starches. While pancreas and islet transplants end reliance on insulin injections for some, there is a shortage of donors. In the United States, there are more than 30,000 new cases of type 1 diabetes each year but only 3,000 potential donors whose pancreases are suitable. Currently, there is no cure for diabetes.

Stem cells offer promise to those with diabetes. If stem cells could be cultivated to become cells that produce insulin, they could solve the problem of donor shortage. If a stem-cell therapy could be developed, it would also help relieve diabetes-related diseases of the kidneys, eyes, nerves, and veins.

To treat diabetes, stem cells need to be cultivated into insulin-producing cells. Once that has been accomplished, researchers expect to transplant stem cells that have been cultivated into insulin-producing cells into diabetic patients. Currently, those who receive transplants must take drugs that suppress the immune system. If a persons own stem cells could be cultivated and used for transplant, those drugs would not be needed. Ultimately, researchers hope to cure diabetes.

Cardiovascular diseases affect nearly 62 million people and is the number-one cause of death in the United States.

Stem cells offer hope to those with heart disease because they might be able to replace damaged cardiac muscle or stimulate the growth of new heart-muscle cells from existing progenitor cells. Because natural regeneration of heart muscle is very inefficient, those who now suffer from a heart attack, from congenital heart disease, or from congestive heart failure have few treatment options. And while heart transplants potentially could help more patients, the supply of organs is limited.

Clinical trials using a patients own stem cells, derived from bone marrow, have already been carried out in United States and Europe, but few grafted cells survive and the benefits are very modest. Current work by stem cell researchers at the University of Minnesota focuses on identifying cardiac progenitor cells and devising new methods to create cardiac progenitor cells from embryonic stem cells or induced pluripotent stem cells.

Liver diseases such as cirrhosis and hepatitis affect 25 million people in the United States and represent the seventh most common cause of death in the United States. Liver transplantation can help some but there is an extreme shortage of transplantable organs. Although more than 18,000 people currently await liver transplantation in the United States, only 5,000 organs will be transplanted in the next year.

Stem cells offer promise both to people born with liver problems and to those who develop liver disease later in life. Those born with liver disease caused by a genetic error potentially could be treated by a relatively small amount of liver cells. These cells could relieve the symptoms of liver disease or the genetic error could potentially be corrected by gene therapy.

In cases of acute liver failure in adults, stem cell therapies might be used to support the liver for a period of time. If the therapy works, patients livers would gain time to recover. There are indications that some forms of viral hepatitis might be treated with stems cells as well.

Researchers at the U are exploring using stem cells in a liver-support device, repairing genes with liver stem cells, and infusing stem cells into liver portal veins. A team focusing on liver disease has made progress in the areas of liver support and gene repair. Some disease treatments may be limited to support but other diseases might be cured with stem cells. Applicable treatments are still five or more years in the future; at this time, there are no plans for human clinical trials.

Theres a mistake in some of these genes. And if we could rewrite that code, Alzheimers, Parkinsons, liver conditionsit would work for all of them. Jakub Tolar, MD, PhD

University of Minnesota researchers are focusing on finding novel treatments for Parkinsons disease using stem cells. Parkinsons disease, which affects a million people in the United States, often begins as a tremor in the hands or feet. Patients later develop trouble with walking and other daily activities as control over the body erodes. While some patients manage their symptoms, there is no cure for Parkinsons disease.

Stem cells offer hope to those with Parkinsons disease, which is caused by the loss of nerve cells in the brain. These nerve cells produce a neurotransmitter called dopamine. If stem cells can be cultivated to become these dopamine-producing nerve cells, researchers believe that they could replace the lost cells.

Other disorders of the brain or nervous system that might be treated with stem cells include stroke, ALS (Lou Gehrigs disease), multiple sclerosis, Huntingtons disease, Alzheimers disease, and spinal cord injuries.

The treatment method being explored is transplanting appropriate cells into the target sites of the brain that need dopamine. Because Parkinsons disease is caused by the failure of one type of cell to do its jobthe dopamine-producing cells in the thalamusParkinsons is believed to be one of the most likely beneficiaries of stem cell research.

Treatments for humans are still years away. At this time, it is hard to pinpoint when human clinical trials might begin, as complex research often encounters unexpected hurdles. With current progress in stem cell research, however, researchers believe they may one day cure Parkinsons disease.

The rest is here:
The Promise of Stem Cells | Stem Cell Institute ...