Category Archives: Texas Stem Cells

22 Jun 2020

Why do some people with AD slide rapidly into severe dementia, while others decline gradually over more than a decade? Part of the answer could come down to which biochemical forms of tau inhabit a persons brain, suggests a study published June 22 in Nature Medicine. Among postmortem brain samples from people with advanced AD, Bradley Hyman at Massachusetts General Hospital in Charlestown and colleagues found a striking variability in taus ability to seed aggregation. The scientists tied aggregation-prone forms of tau in the postmortem brain to a more rapid course of disease during life. They pegged large, soluble tau oligomersphosphorylated on specific residuesas the most hazardous species. Antibodies trained against these types of tau stopped its aggregation. The findings cast taus behavior as a major prognostic determinant for AD, and support the concept of targeting these troublesome forms of the protein with therapeutics.

This is a well-designed study underlining once more the importance of the soluble tau oligomeric assemblies over long tau filaments in Alzheimers disease, as well as heterogeneity in tau oligomers, commented Rakez Kayed of the University of Texas Medical Branch in Galveston.

The study clearly highlights the complexity and heterogeneity of tau proteins in people with AD, noted Hilal Lashuel of cole Polytechnique Fdrale de Lausanne in Switzerland. The complexity calls for cautious interpretation of the findings, Lashuel added, noting that enigmatic tau oligomers are in dynamic equilibrium that can be influenced by disease stage and all manner of other factors. It would be very difficult to identify a specific oligomer species that consistently correlates with tau propagation or disease progression, he said.

Throughout the course of AD, neurofibrillary tangles of tau overtake the brain in a stereotypical sequence (Braak and Braak, 1991). Fueled at least in part by a templated misfolding mechanism, the propagation of tau tangles throughout the brain is tied closely to clinical progression of the disease (Jan 2020 news; May 2019 news;Jun 2019 news).

But even among people with the typical, amnestic form of AD, how aggressively their clinical disease gets worse varies strikingly from one person to the next (Komarova et al., 2011). This not only creates uncertainty for patients and their families, but also poses a risk for clinical trials, whose success depends on being able to measure a treatment effect within a set time, typically six months for Phase 2. Too many slow progressors in a trial cohort can sink a study even if the drug did what it was intended to do. Might molecular variations in tau speciesparticularly those that influence its propagationexplain this clinical heterogeneity?

Diversity of Decline. CDR-SOB scores worsened (increased) at vastly different rates in people who ultimately died with advanced AD. Some never reached the maximum score before they died. [Courtesy of Dujardin et al., Nature Medicine, 2020.]

First author Simon Dujardin and colleagues addressed this question by probing myriad aspects of tau taken from the postmortem brains of 32 people who had died in the advanced stages of AD. At the time of death, each had extensive tau tangles in the brain, at Braak stage V/VI. However, their clinical trajectories had been remarkably variable. Their age at onset ranged from 45 to 81, and the time between symptom onset and when they died ranged from five to 19 years. Their rates of cognitive decline, as gauged by serial tests on the clinical dementia rating scale sum of boxes (CDR-SOB), also varied widely.

The researchers started by measuring the capacity of tau to seed aggregation in biosensor cell lines. Equipped with a tau fragment tagged with fluorescent donor and acceptor molecules, these cells light up when potent seeds spark aggregation (Oct 2014 news). Although the researchers normalized the amount of tau used from each brain, they found wide variation in seeding activity. It ranged by an order of magnitude across samples. Notably, the three samples with the highest seeding activity came from people who carried two copies of ApoE4, suggesting the risk factor influences tau propagation.

Seed Span. When added to biosensor cell lines (left), soluble tau proteins extracted from the brains of people with AD were strikingly heterogeneous in a seeding assay. [Courtesy of Dujardin et al., Nature Medicine, 2020.]

The physiological relevance of this cell-based biosensor assay has been challenged recently (May 2020 news). So as not to rely entirely on this assay as a proxy for taus propagation potential, the researchers also conducted a series of alternative seeding experiments with a subset of the samples deemed low, intermediate, or high seeders based on the biosensor assay. Whether treating primary neuron cultures with these extracts or injecting the extracts directly into the brains of mice expressing P301S tau, the researchers observed similar relative trends in seeding activity among the samples. This suggested that the cell-based biosensor assay provided a meaningful gauge of the relative potency of tau seeds in each sample.

Planting the Seed. Tau extracted from human brain samples with low, moderate, or high seeding activity on biosensor assays triggered similar trends of tau aggregation when injected into the P301S mouse brain. [Courtesy of Dujardin et al., Nature Medicine, 2020.]

To figure out what about tau determines its seeding potency, the researchers subjected tau in the brain extracts to a barrage of biochemical assays and cross-referenced the results with the seeding activity gleaned from biosensor assays. They report that seeding activity correlated not with a persons amount of total tau, but with levels of oligomeric, hyperphosphorylated tau in each sample. Compared with intermediate or low "seeders," high seeders had an abundance of soluble, high-molecular-weight tau oligomers.

Using mass spectrometry, the researchers mapped the phosphorylation landscape of tau across samples, noting that tau doubly phosphorylated on Thr231 and Ser235, or singly phosphorylated on Ser262, correlated with seeding activity. Curiously, neither ptau-181 nor ptau-217the species that rise in the cerebrospinal fluid in the preclinical stages of ADwere significantly tied to seeding activity (Mar 2020 news; Apr 2020 conference news).

Does tau seeding activity, or any of its biochemical correlates, relate to a patients clinical progression? Indeed, the researchers found that the higher the tau seeding activity, the steeper the persons rate of decline on the CDR-SOB, and the younger his or her age at symptom onset. The abundance of oligomeric, hyperphosphorylated species of tau also correlated with disease progression, as did levels of the same phospho-tau species that associated with seeding activity.

Collectively, tau seeding activity accounted for about 25 percent of the clinical heterogeneity among people with typical AD, the researchers reported. This suggests that tau antibodies that block tau seeding might also stem clinical progression of the disease. To identify antibodies that might do the trick, the researchers used a panel of seven antibodies trained against different parts of the tau protein, or against specific phospho-residues, to deplete tau from the brain extracts, then tested the remaining seeding activity. They found that some antibodies quashed seeding more effectively than others, and that there was significant variability between samples. Overall, antibodies such as AT8 and PHF1, which bind to pathological forms of tau, inhibited seeding most consistently across samples.

At first glance, the heterogeneity in taus seeding capacity and biochemical forms across AD brains may seem at odds with cryo-electron microscopy studies, which identified two predominant conformations of tau fibrils in people with AD (Jul 2017 news). Thats not the case, Dujardin noted. Soluble tau oligomersnot fibrilsare the source of taus biochemical variability in this postmortem study. He said it would be fascinating to examine tau oligomers via cryo-EM.

Lashuel noted that the researchers did not analyze insoluble fractions of tau in their assays, biasing them to zero in on soluble species. He suggested that attention be paid to understanding the near-total lack of seeding activity in the "low seeders," who still ultimately developed AD. Perhaps more answers would be found in insoluble fractions, he said.

Why is one persons tau not like anothers? Dujardin suspects genetic differences that influence cellular processes such as degradation and autophagy, which may selectively degrade certain forms of tau. Though microglial function theoretically influences these pathways, Dujardin noted that inflammatory markers in the 32 brains did not correlate with seeding activity, at least at this end stage of disease. Individual differences in kinase activity could also influence which phosphorylations tau accumulates over a persons lifetime.

How might researchers leverage the findings to inform a persons prognosis? Dujardin noted several possibilities. A handful of studies have managed to detect seeding activity in tau derived from CSF, though Dujardin noted that these assays need to become more sensitive (Takeda et al., 2016). In lieu of directly measuring seeding activity, perhaps quantification of tau oligomers, and/or specific phospho-tau species associated with seeding activity, could serve the same purpose.Jessica Shugart

See more here:
Tau: Why Alzheimer's Worsens Fast in Some, Slowly in Others - Alzforum

In retrospect, December 2019 seems like an altogether different era now. For most of the U.S. population, at least, those were the halcyon days when students were doggedly completing final exams and papers, teachers were grading and looking forward to winter break, shoppers were checking off gift lists online and in stores, the faithful were making pilgrimages to holy sites, families were crisscrossing states and oceans to visit loved ones, football fans were celebrating the NFL playoffs, tourists were crowding into theaters on and off Broadway, crafters were selling their wares at holiday bazaars, farmers were repairing their equipment, and friends were meeting up for peppermint and eggnog latts.

On New Years Eve, meanwhile, the China Country Office of the World Health Organization (WHO) received reports that a cluster of pneumonia cases had presented in the city of Wuhan, in Hubei Provinceplace names that have since become ominously familiar but were then still unknown to many Americans. Six days later, the cause of the illness was still obscure, but by January 7, 2020, scientists in China had already isolated the pathogen and shared its full genetic sequence with the global scientific community. They identified it as a novel coronavirus (2019-nCoV).

Combining visual metaphor and perhaps not a little irony, coronaviruses are named for their crown- or halo-like appearance when peered at through an electron microscope; corona in Latin denotes an honorific garland worn on the head or else a halo encircling a celestial body, such as the sun. The pathogens, of which there are currently four main types known to affect humans, were first characterized in 1965 and are the source of mild to serious upper respiratory syndromes; some coronaviruses, for example, are known to cause the common cold (as do more than 200 other viruses, such as rhinoviruses). This newest coronavirus, however, had within a week caused 44 patients to seek in-hospital care, with 11 reported as severely ill.

Back in Georgetown, Texas, microbiologist Martn Gonzalez was just one Southwestern scientist who was carefully following updates on the epidemic as news emerged each day in the popular media and within the scholarly community. A novel virus is always cause for keen interest among researchers and healthcare practitioners alike, certainly, but its not necessarily a source of surprise. After all, in reflecting on the long history of human disease, researchers started predicting a pandemic like COVID-19 decades ago and more recently in articles such as The Next Plague Is Coming; Is America Ready? by science journalist Ed Yong and in the 2020 Netflix documentary series Pandemic: How to Prevent an Outbreak (whose first episode, Gonzalez says, is the one to watch if you want an accessible explanation of how a global disease affects communities, how researchers and healthcare providers approach them, and how difficult it is to develop vaccines).

With all the past epidemics and pandemics that weve seen, this was only a matter of time, Gonzalez says. I think most people in the sciences realized this was the case.

Gonzalez was teaching microbiology in January. On the first day of class, he posed the same question he asks at the beginning of every lecture: Has anybody heard anything going on in science? That day, he received a lot of blank stares; his students, like most people across the nation, had not yet started paying attention to the 2019-nCoV coverage, blissfully unaware of how the virus and the disease it causes would soon take center stage during classroom discussions and, of course, disrupt their very lives. But Gonzalez knew that the virus was one to watch: the first case of a 2019-nCoV infection in the U.S. was confirmed on January 20, in Snohomish County, Washington; by the end of the same month, the infected were numbering nearly 10,000 in at least 21 countries, and the WHO had declared a public health emergency of international concern. So he asked his students to start sharing the latest information at the top of each class meeting.

It didnt take long, he says, for students to start realizing that this was going to be much bigger than we originally thought.

Transmission electron microscopic image of an isolate from the first U.S. case of COVID-19. The spherical viral particles, colorized blue, contain a cross-section through the viral genome, seen as black dots. Credit: CDC Image Library, ID# 23354.

On February 11, 2020, the International Committee on Taxonomy of Viruses (ICTV) announced that, given the genetic relationship between the novel coronavirus and the coronavirus responsible for the 2003 outbreak of SARS, the new pathogen would be named severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. The same day, the WHO christened the disease caused by SARS-CoV-2 coronavirus disease 2019, or COVID-19.

Meanwhile, Gonzalez and his students discussed how viruses, the smallest of all microbes, consist of DNA or RNA surrounded by a protein coat called a capsid and sometimes, as with SARS-CoV-2, by a lipid envelope that can be dissolved with soap, thereby destroying the entire particle (TL;DR? wash those hands!). They knew how viruses attach to the plasma membranes of living host cells and hack the cells mechanisms to replicate before detaching and invading other cells, usually destroying those cells, damaging tissues, and sickening or even killing the host organism. They discussed how viruses spread through the human population in many ways. For example, some can be passed on by skin-to-skin contact. Others can be transmitted via contaminated surfaces (disinfect those countertops!). They can spread through exposure to others bodily fluids and secretions, such as through sharing needles, sexual contact, or coughing and sneezing (again, wash those hands! but also wear masks to keep from infecting others!). And viruses can be carried by vectors, or disease-bearing organisms, such as mosquitoes, fleas, or bats, the last of which may have served as a reservoir for SARS-CoV-2 before it jumped to an intermediate host and then eventually infected humanswho are also possible vectors.

It was a great learning experience, Gonzalez reflects.

But he noticed that as the days went by, his students began expressing frustration about the governmental and public responses to the outbreak. By late February, the number of confirmed cases of COVID-19 had topped approximately 84,000 in at least 56 countries, and the death toll had climbed to 3,900, but many nations, including the U.S., were slow to react and failed to implement a unified, strategic approach to testing and prevention based on classic epidemiological models.

Gonzalezs students wanted to know why. And I told them, We can talk about politics, but I have no idea why were approaching this the way we are, he remembers.

They also wondered aloud whether the novel coronavirus was something to be worried about considering comparisons that were being drawn between COVID-19 and seasonal influenza. Gonzalezs response was to remind them of the flus grave statistics: the Centers for Disease Control and Prevention (CDC), for example, estimates that in the U.S. in 20162017 alone, 29 million people contracted symptoms of the seasonal flu, with 14 million seeking medical care, 500,000 requiring hospitalization, and 38,000 dying. Moreover, many people worldwide have developed immunity to seasonal flu strains, and flu vaccines exist to combat infection. By contrast, although mortality rates are impossible to confirm while an epidemic or pandemic is ongoing, the risk of death from COVID-19 appears to be higher than that from the flu. In addition, it remains unclear even now whether those who have survived COVID-19 have developed immunity, how long that immunity lasts, when a safe vaccine will be available, and when a large enough swathe of the global population will be inoculated to develop herd immunity.

Gonzalez says that his students became more educated in all this. They became aware of the power of knowledge. And they became aware of the stress of knowledge.

Given the store of knowledge scientists have developed based on previous epidemics, including the more recent outbreaks of coronavirus-caused diseases such as SARS (in 2003) and MERS (Middle East respiratory syndrome, in 2012), you would think that we would have been more prepared and known how to respond more quickly. And countries such as Taiwan, New Zealand, Costa Rica, Iceland, Norway, and Denmark have been highly successful in limiting both infection and mortality because they relied on science, prioritized public health, coordinated responses among institutions, acted swiftly, and garnered the trust and cooperation of its citizens.

But elsewhere, as in the U.S., Gonzalez says, its been clear we havent learned the lessons of past outbreaks. A significant etiology of the chaotic and ineffective response has been misinformation, and he believes that platforms such as Nextdoor, Facebook, Twitter are just some of the vectors to blame for the spread of false or misleading information. One of the things that concerns me is were very much a social-media society now, he explains. Social media can be an incredible tool to get your message out, but if your message is filled with misinformation, its devastating to the cause . Lives are at stake here.

Social media can be an incredible tool to get your message out, but if your message is filled with misinformation, its devastating to the cause . Lives are at stake here.

Ironically, one flagrant inaccuracy Gonzalez saw floating about was a comment about vaccines in which the poster opined that scientists were lying. Understandably, Gonzalez had to refrain from responding, and he now limits his media diet to reporting by the CDC and the BBC, the British news channel. I havent checked it recently, but I can imagine my blood pressure is up a little bit, he laughs.

In the absence of accurate and clear communicationnot to mention the lack of other standard epidemiological strategies, including widespread reliable testing, quick diagnosis and quarantine, and contact tracing and isolationthe U.S. federal response to the disaster has been, well, disastrous. The most glaring symptom of this failure is that the countrys tally of infections and deaths far surpasses that of any other country: on May 24, the U.S. exceeded 1.6 million confirmed cases and 100,000 deaths, and at the time of this publication, a day shy of one month later, that death toll has risen to 120,225, with well more than 2.29 million confirmed cases. Another complication of the U.S.s messy response has been a host of avoidable draconian interventions with wide-ranging impacts on human behavior and the economy, such as social distancing, stay-at-home mandates, and school and business closuressacrifices that became necessary to flatten the curve (i.e., reduce the number of infections to prevent overburdening the healthcare system) but would also lead to upheaval in the lives and learning of Southwesterns own staff, faculty, and students.

But one other adverse effect of the lack of a coordinated national response has been a shortage of life-saving medical supplies. States, for example, were left to compete for ventilators, and healthcare providers were forced to reuse or go without personal protective equipment (PPE), jeopardizing the lives of the very people who can actually treat the disease. I think what is most frustrating is were putting people on the frontlines of this pandemic in danger, Gonzalez shares. He felt so strongly about the supply crisis, in fact, that he broached to his colleagues in the Biology Department a way they could help. I said, We have all these gloves were not going to be using because were not having labs or classes, and we have a good stock, so we can donate them! he recalls. The biology faculty consulted with Southwesterns administration, and their colleagues in the Chemistry Department volunteered to donate their equipment as well. Its one of those things where youre saying, I shouldnt have to be doing this, but were doing it, Gonzalez adds.

Despite his and his students deep concerns about the way the COVID-19 pandemic has been handled, Gonzalez saw some glimmers of positivity and hope when stay-at-home orders were in effectfrom the community wanting to support local restaurants by ordering takeout and neighbors offering to pick up items from the grocery store to help protect those who are greater risk of developing serious illness, such as those 65 years and older or those with underlying medical conditions, such as diabetes, heart disease, or compromised immunity. From that standpoint, its been very uplifting for me, he says. Some of the community is wanting to make a difference and looking to help.

He also celebrates the many breakthroughs of his STEM colleagues around the world, who have worked tirelessly in the past few months to advance knowledge of COVID-19 and over the years and decades to improve our learning about infectious diseases more broadly. He loves seeing publications such as Nature encouraging scientists to share their latest findings to expand our understanding and build this knowledge base. And he looks forward to discoveries that might be just around the corner, such as a universal vaccine that provides long-term immunization against all influenza types or a platform vaccine, long advocated by National Institute of Allergy and Infectious Diseases Director Anthony Fauci, which would enable researchers to begin the first phase of clinical trials for new vaccines within months rather than years. You have no idea how much pride I had when it was less than two weeks after [the COVID-19 pandemic] started rolling that the global scientific community came out with a genetic sequence for [SARS-CoV-2], he says excitedly. Thats why I fell in love with science: its truly a community. When we publish papers, we police each other by doing peer review, and people will try to reproduce some of your results. Weve been doing this for a long time, and its worked. Ive been really happy with that.

You have no idea how much pride I had when it was less than two weeks after [the COVID-19 pandemic] started rolling that the global scientific community came out with a genetic sequence for [SARS-CoV-2].

Gonzalez says that we still have much to learn about SARS-CoV-2 and COVID-19, but even after the current pandemic ends, we cannot be complacent going forward; instead, we must apply the lessons of yesterday and today. We can look at some of the earliest Old World infectious diseasesthings like dengue fever, yellow fever, and malaria. It took something like 300 years for those three diseases to be found on most places on this planet, he explains. And then you look at the global society we are now and look at some of these new emerging infectious diseases, such as West Nile virus, Zika virus, and Chinkungunya virus. Its taken them less than 16 years to be found pretty much on a very large percentage of this Earth.

Moreover, Gonzalez adds, we have yet to fully comprehend the many twists and turns of infectious disease. For example, how might climate change accelerate or exacerbate the spread of such illnesses? When will the next single mutation in a known virus enable the sudden transmission of the pathogen from animals to humans, as was the case of SARS-Co-V-2? We were fortunate that the coronavirus that causes MERS, a disease with a 35% casefatality rate, did not easily transfer between human beings, but what if a more robust MERS-CoV-2 were to emerge? And what if Ebolaa fast-spreading disease with quickly manifesting symptoms and a shocking mortality rate as high as 90% in some WHO estimateswere suddenly contagious when carriers were asymptomatic (i.e., not exhibiting symptoms)?

We need to be prepared for this, he asserts. This is not something where we can sit there and say, As soon as this starts happening, well jump. We need to be working at this right now.

However, scientific discovery and innovation require opportunity and resourcesincluding both money and time. The medias pursuit of big stories and eye-catching headlines might suggest that scientific progress happens by leaps and bounds within days or weeks; the anxious public may be impatient for answers about a public-health crisis that is shaping individual lives. Nevertheless, good science requires time: time for research and development, time for experimentation and failure, time for correcting errors and replicating results, and time for collaboration and peer review. Yes, [scientists] can figure it out, but it takes time, Gonzalez says. Science is not do one experiment and have a result. It just didnt work that way. I wish it did! he laughs.

And with the COVID-19 pandemic, that scientific progress is actually happening fairly quickly, regardless of what naysayers might think or say. But because of the relatively rapid pace of research on SARS-CoV-2 and COVID-19, scientific findings and recommendations shared with the public can change, sometimes in the course of just weeks. After all, scientists are constantly expanding on previous work, discovering new phenomena, and drawing conclusions from the latest evidence. Their work can also be misinterpreted and misreportedaccidentally or intentionallyby journalists, pundits, and social-media frequenters. And in a heightened atmosphere characterized by fear of the unknown and suspicion of the very science we should be relying on, Gonzalez knows moving forward will require a lot of education.

As Ive always said, trust the science, he says. The science will police itself and will let you know if theres something you shouldnt be listening to.

Gonzalez will continue urging his students to use the communication skills theyve gained at Southwestern to share their scientific knowledge with their families, friends, and communities.

In the meantime, Gonzalez will continue urging his students to use the communication skills theyve gained at Southwestern to share their scientific knowledge with their families, friends, and communities. Its a practice that he hopes will prevent his students from caving to fear, will keep their circle of connections informed, and will ensure the health and safety of their loved ones. Says Gonzalez, Thats the one thing Ive really told my students: Whether this [pandemic] was going on or not, youre going to be part of a community, and there are times when a community requires a voice of reason. Your job is to go out there, use what youve learned, and bring that voice. I hope they do it; I really do.

Bibliography/further reading

Go here to see the original:
Scholarly Perspectives on COVID-19, Part 1: This Was Only a Matter of Time - Southern Newsroom

Hospital Galenia in Cancun, Mexico, where Celltex administers autologous mesenchymal stem cells to clientsKERRY GRENSOn a main thoroughfare running along the east side of Cancun, Mexico, sits Hospital Galenia, a small, private facility with crisp, white walls and slick marble floors. On a Friday morning in February, the lobby is quiet, its palm-filled courtyard unoccupied, belying activity in parts unseen, including an emergency room and a maternity ward.

Cancuns beaches draw in visitors by the millions each year, while Galenia attracts a distinctive kind of tourist: those seeking health treatments not sanctioned by the U.S. and governments elsewhere. A number of medical tourism companies operate out of Galenia, including Houston-based Celltex Therapeutics, a company that offers stem cell therapies to mostly American customers. Celltex claims to use patients own mesenchymal stem cells (MSCs) to treat diseases as wide-ranging as amyotrophic lateral sclerosis (ALS), renal failure, and chronic obstructive pulmonary disease (COPD).

Originally, Celltex administered cells to its clients out of a laboratory site in Sugar Land, Texas. But the company had to cease offering such treatments in Texas in 2013 after the US Food and Drug Administration (FDA) sent Celltex a warning letter in 2012 stating that the patient-derived cells it was harvesting and injecting were considered drugs under US federal law, thereby requiring clinical trials and regulatory approval. The FDA review also revealed that the company mishandled the cells, failing to keep them in sterile conditions and mislabeling containers.

Rather than cede to federal laws and go the standard drug-approval route through the FDA, Celltex instead shifted its clinical operations south of the border, shipping ready-to-use MSCs in syringes to Hospital Galenia. But with a newly passed law in Texas known as Charlies Law, Celltex might have the opportunity to resume treating patients stateside. The new law could allow Texas clinics to administer certain non-FDA-approved stem cell treatments, like those offered by Celltex, to select patients.

State law is subordinate to federal FDA rules, according to the agency. Therefore, the new Texas stem cell law potentially sets up a state-federal conflict. Paul Knoepfler, a stem cell biologist at the University of California, Davis, and coauthor of a recent study that analyzed stem cell clinics in the U.S., tells The Scientist that proponents of direct-to-consumer stem cell clinics could use the law as an opportunity to challenge the FDAs authority, which could result in a federal court case.

While Texas is loosening regulations on unproven stem cell treatments, the FDA and health authorities in other countries are going in the opposite direction.

Celltexwhose board of directors includes Texass former first lady, Anita Thigpen Perrywas actively involved in the bill, according to a Celltex spokesperson. The law is a step in the right direction, according to the firm, but still far from a law which would allow us to provide high-dose adult stem cell banking and therapy in the United States.

Direct-to-consumer stem cell clinics, influential Texas politicianssome with ties to Celltexand some patients eager for alternative therapeutic options applaud the law. But scientists question the cells efficacy, and bioethicists voice concerns about selling a therapy before the evidence is all in. Without rigorous testing and FDA oversight, critics say, there are no guarantees that these direct-to-consumer stem cell clinics abide by rigorous laboratory practices and that the interventions are not putting patients at risk.

Its true that we are very excited about the ability to develop effective new therapies using stem cells but there is a tremendous amount of research required to figure out how to do this effectively and safely, says Sean Morrison, a stem cell biologist and director of the Childrens Medical Center Research Institute at the University of Texas Southwestern Medical Center in Dallas. There are many companies short-circuiting that process and selling patients unproven entities that they have not shown to be effective nor safe. In some cases, the unproven therapies are scientifically implausible based on what we know about the biology.

According to Celltex, the company treats about 400 to 500 people each year using MSCs harvested from the patients own belly fat. The cells are then purified, expanded, and frozen in Texas before being infused intravenously or injected into the affected tissue. According to the medical director of Celltexs Galenia clinic, Gabriel Salazar, most patients come for relief of inflammatory conditions, especially arthritis. There are people who come for wellness as well, says Salazar. They arent sick, but they have risk factors.

The physiological mechanism of MSCs is unclear. Salazar says they initiate anti-inflammatory pathways, a phenomenon that researchers have observed in vitro in the lab. From animal models, scientists understand that these are cells that regulate the microenvironment at sites of injury . . . but no one really understands how they function in vivo, says Arnold Caplan, an MSC researcher at Case Western University.

All [of our clients] have received improvements, some minimally and some miraculously. And no one has had a problem.David Eller,CEO, Celltex

Clinicaltrials.gov lists 243 ongoing MSC trials, including some in the U.S., sponsored by industry, the National Institutes of Health, and others. Yet there are no FDA-approved therapies using MSCs for any condition. The FDA, for its part, is studying MSCs to develop standardized isolation methods and to learn how MSCs behave when injected into the body.

Anecdotal testimonials from clients of Celltex and other firms abound, but rigorous clinical evidence is hard to come by, as companies selling stem cell therapies dont often publish in peer-reviewed journals. In fact, there are no published data on MSCs efficacy in ameliorating arthritis or the numerous other conditions that patients pay Celltex to treat. Thus far, Celltex has one publication documenting MSC use in patientsa 2017 case report of two individuals with a nervous system disorder that suggests the autologous adipose-derived MSCs they received resulted in symptom improvements.

Celltex CEO David Eller says the company has safely administered MSCs to more than 4,500 clients. All of them have received improvements, some minimally and some miraculously, he tells The Scientist. And no one has had a problem. In opposition to the FDAs stance, Eller considers clinical trials a waste of patients time. We can wait another decade or more for costly clinical trials and watch as our loved ones deteriorate, or we can do something about it now. In our eyes, doing nothing is the real risk, he writes on the Celltex website.

Nevertheless, Celltex has pledged to conduct its first clinical trial. Just last month (February 27), the firm announced that the Comisin Federal Para La Proteccin Contra Riesgos Sanitarios Comisin de Autorizacin Sanitaria (COFEPRIS, the Mexican equivalent of the US FDA) had given the go-ahead for Galenia to start a clinical trial in patients with osteoarthritis and rheumatoid arthritis. The Phase 2 study will use Celltexs protocols to generate cells in quantities never possible for use in therapies for vascular, autoimmune, and degenerative diseases, as well as injuries, according to a company press release.

Details on the trial are scant. The press release states that the trial will measure the quality of life (QoL) of subjects prior to and after receiving the therapy. Celltex tells The Scientist that the trial will have a safety and toxicity monitoring component and that participants will not incur cost of the cell procedure. According to the Celltex website, the company charges $6,500 to obtain, process, and store a clients MSCs for one year, while the pricing for an injection varies depending on each individuals situation.

Im all for investigating QoL self-assessments in the context of clinical research, says Leigh Turner, a bioethicist at the University of Minnesota who studies direct-to-consumer stem cell clinics, but one obvious concern in the case of this particular study is that it will do little more than capture a placebo [effect].

According to Turner, Celltex is not the first US business selling unapproved stem cell interventions to conduct a QoL study rather than one specifically designed to test for safety and efficacy endpoints. For marketing approval, the FDA requires that stem cell products be tested for safety and efficacy and that the company developing the product file an IND application with the agency. Yet trials can be listed on registries such as clinicaltrials.gov whether or not they comply with FDA regulatory standards and safety oversight.

I hope [Celltex] pursues an Investigational New Drug application [IND] in the U.S. and conducts a placebo-controlled, double-blinded study, writes Knoepfler in an email to The Scientist. If their product is safe and clearly effective, such a rigorous study could prove that fairly conclusively.

Human mesenchymal stem cells with nuclei labeled blue and actin filaments greenFLICKR, ENGINEERING AT CAMBRIDGE

The new Texas stem cell law has yet to go into effect; the states Health and Human Services Commission is still developing the procedures of how the law will be implemented. As Celltex and other direct-to-consumer stem cell companies wait for lawmakers to clarify details on the new rules, Celltex will continue with its cell-banking operations in Texas and its infusions in Mexico, a Celltex spokesperson tells The Scientist.

According to State Senator Paul Bettencourt (R-Houston), an author of the bill, the plan is for each stem cell treatment course to be reviewed by an Independent Review Board (IRB). After a favorable review, the treatment could then be administered in one of the hundreds of medical institutions in Texas.

The Texas law is unique in its permissiveness, says Turner. A new law in California, which took effect January 1, requires that direct-to-consumer stem cell clinics disclose to potential customers that their products are not approved by the FDA. Other states appear to be looking for ways to better protect patients and consumers instead of looking for ways to lower regulatory standards, writes Turner.

While Texas is loosening regulations on unproven stem cell treatments, the FDA and health authorities in other countries are going in the opposite direction, focusing more oversight and scrutiny on direct-to-consumer stem cell clinics. The FDA has recently warned consumers about stem cell clinics touting unproven treatments, and in August 2017, the FDA commissioner announced plans for better enforcement of federal laws and oversight of stem cell clinics. Australia recently announced a higher level of stem cell clinic regulation, as have health agencies in Canada and India.

To be a candidate to receive the therapy under Charlies law, the patient must have a severe, chronic disease or be terminally ill. And the treatment must be registered in a clinical trial database somewhere in the world. According to Bettencourt, the next step is for the Texas Medical Board to draw up the process for how to evaluate and oversee each patients case.

But the bill does not include any details on product oversight or quality control, and reporting by The Scientist reveals questionable practices.

When The Scientist spoke to Eller, he said that Celltex uses the MD Anderson Flow Cytometry Facility weekly to validate that the cells are 100 percent patient-derived MSCs. And in follow-up emails, a spokesperson for Celltex also stated that members of the MD Anderson core staff independently conduct quality control and validation.

However, the cytometry facility had a different story.

Scott Melville, an MD Anderson spokesperson, tells The Scientist that Celltex has paid to use the public Flow Cytometry Facility since 2015, but that that no one at the facility independently assesses the quality and content of the [Celltex] samples. According to MD Andersons recent records from the last several months up to March 23, 2018, Celltex used the facility for two hours on November 2, 2017, and for one hour each on January 18 and January 19, 2018.

Critics of the Texas stem cell law say that the language in the bill is too vague and are skeptical that there will be enough independent scrutiny to make sure patients are not exposed to unsafe treatments. Im concerned that businesses could use it to make money by putting patients at risk, says Knoepfler.

Reporting from Mexico by Kerry Grens

Read more:
Texas Stem Cell Law Opens Door for Controversial Treatments

By Charles PillerJun. 8, 2020 , 7:00 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center.

Three unlikely collaborators are at the heart of the fast-moving COVID-19 research scandal, which led to retractions last week by The Lancet and The New England Journal of Medicine (NEJM), and the withdrawal of an online preprint, after the trove of patient data they all relied on was challenged. The three physician-scientists never were at the same institution nor had they ever before written together, but they are the only authors in common on the disputed papers, and the other co-authors all have ties to at least one of them. Their partnership, which seized a high-impact role during a global public health crisis, has now ended disastrously.

The first author for both retracted papers was cardiac surgeon Mandeep Mehra, an eminent Harvard University professor who works at Brigham and Womens Hospital (BWH) and is known internationally for cardiovascular medicine and heart transplants. He provided the kind of gravitas that can fast-track papers to leading journals. In a statement provided by BWH, Mehra said he had met another of the trio, cardiac surgeon Amit Patel, in academic and medical circles, and that Patel had introduced him to Sapan Desai, a vascular surgeon and founder of Surgisphere, the tiny company that supplied the data. Journal disclosures, however, also indicate Mehra received compensation from Triple-Gene, a gene therapy company Patel co-founded to develop cardiovascular treatments.

Desai publicly aspired to combine big data and artificial intelligence (AI) in ways that he said can replace randomized controlled clinical trials. For a brief moment, it seemed that Surgispheres enticing data set, said to include nearly 100,000 detailed patient records from about 700 hospitals on six continents, would settle questions about the possible benefits of various drugsincluding the controversial antimalarial hydroxychloroquinefor COVID-19 patients.

Patel once apparently headed cardiac surgery at the University of Miami Miller School of Medicine. A university press release announcing his arrival in 2016 is no longer posted on the university website, however, and the school has not confirmed his job duties there. More recently, he has been a volunteer adjunct professor at the University of Utah. But, as STAT first reported yesterday, Patel tweeted on Friday that he had severed his relationship with the university, which a school spokesperson confirmed. In recent years Patel has developed and commercialized experimental stem cell therapies purported to cure heart problems, reverse aging, or treat sexual dysfunction. He is also part of a network of physicians that just launched a trial to use stem cells from umbilical cord blood to treat COVID-19 patients.

Normally co-authors of high-profile papers share subject area expertise or have clear professional ties, says Jerome Kassirer, chief editor ofNEJMduring the 1990s. He calls the collaboration of the apparently disparate individuals completely bizarre, and a red flag that the studies warranted intensive scrutiny that the journals failed to provide.

None of the three co-authors responded to requests for comment. Patel spoke with aSciencereporter initially but said he wanted to wait for audits of the Surgisphere data to comment, and Desais spokesperson stopped communicating after the retractions. Still, interviews with former colleagues and a long paper trail shed some light on each of them.

Desai had a history of convincing respected researchers of his skill and integrity. One of them, Gilbert Upchurch, department of surgery chair at the University of Florida, wrote last year in a journal commentary that he had never met Desai but had nonetheless mentored him remotely and developed an online friendship with him. Upchurch placed the scientist in a group of amazing and talented young vascular surgeons.

Illinois court records show Desai is facing two medical malpractice lawsuits filed last year. He told The Scientist that he deems any lawsuit naming him to be unfounded.

Desai has a history of big aspirations and entrepreneurial venturessome short-lived. His science-fiction blog, corewardfront.com, was meant to find the most parsimonious route for mankind to establish a meaningful presence in space. In 2009, he wrote that the site would publish fiction grounded in facts and reality, adding, the scientific method must be followed religiously. The blog is no longer published.

As a student, Desai won several small National Institutes of Health (NIH) grants for studies of the vestibular system. He started Surgisphere in 2007, when he was a medical resident at Duke University. Surgispheres initial products were medical guides and textbooks, although Desai has said he was working on big data projects for the company from its birth. In 2010, under the firms auspices, he founded the Journal of Surgical Radiologywhose editors included researchers with well-established publishing records. It folded in January 2013. Articles from the journal were cited only 29 times in its history, according to Scimago, a journal rating service. Yet an undated Surgisphere web page, no longer accessible online, said the online-only publication had 50,000 subscribers and nearly 1 million page views monthlywhich would have placed it in elite company in academic publishing.

Surgisphere appears over time to have shifted its efforts into developing a database of hospital records that could be used for research. When the pandemic erupted, Desai declared that his data set could answer key questions about the efficacy and safety of treatments. Speaking about the finding that hydroxychloroquine increases mortality in COVID-19 patients, the main finding from the now retracted Lancet paper, he told a Turkish TV reporter, with data like this, do we even need a randomized controlled trial? Soon after, the World Health Organization temporarily suspended enrolling patients for its COVID-19 trial of the drug.

Immediately after the Lancet and NEJM studies appeared, however, critics identified anomalies in the data. And they doubted that a tiny firmwith a scant public track record in AI, few employees, and no publicly named scientific boardcould convince hundreds of unidentified hospitals in dozens of nations to share complex, protected, and legally fraught patient data. Ultimately, despite Desai promising repeatedly to allow an independent audit of Surgisphere, the firm refused to release the raw patient data and agreements with hospitals for an audit, so no one could validate the authenticity of its database.

No hospitals have come forward to acknowledge working with Surgisphere. Indeed, NHS Scotland, which is mentioned as a case study on the companys website, says none of its hospitals worked with Surgisphere and that it would ask the firm to remove an image of a Glasgow hospital from its website.

Science contacted several of Desais current or former employees or colleagues. Most would not comment. But Fred Rahimi, an Illinois podiatrist and co-author of a paper with Desai, praises the surgeon as highly capable for salvaging limbs, and easy to work with. Through his publicist, Desai cited Mark Melin, a University of Minnesota, Twin Cities, vascular surgeon, as a supporter. Before the retractions, Melin called Desai a gentleman of the highest integrity who has nothing to cover up.

But one physician-scientist who worked closely with Desai several years ago, says, Just about everyone who knew him would say: I just didnt have a good feeling about him. After theyd been with him, most people dissociated themselves from him, the scientist says, declining to be named to avoid personal and institutional embarrassment.

In the decade since completing his medical residency, Desai moved from job to jobat Duke, the University of Texas, Southern Illinois University, and two private Illinois hospitals, according to his LinkedIn profile. You might say we should have stopped him, which now seems obvious, Desais former colleague says. We should have found a way to get together and say, Whats going on here? rather than allowing him to move from place to place. We should have done better as a medical community. We looked the other way.

Before and after his stint at the University of Miami, which appears to have started in late 2016 or early 2017, Patels academic home was the University of Utah. He started as a full-time faculty member at Utah in 2008 and kept that position until he left for Miami. The website for Foldax, a heart valve company that he serves as medical adviser, describes him as a Tenured Professor of Surgery in the Division of Cardiothoracic Surgery at the University of Utah School of Medicine and Director of Clinical Regenerative Medicine and Tissue Engineering at the University of Utah.

The university confirmed Patel had tenure there, but says the directorship was an unofficial title. And among more than 100 publications listed on his University of Utah profile, nearly two-thirds were actually co-authored by other scientists who share the same surname. The page was removed from the university website after inquiries from Science.

According to the NIH database, Patel has never received funding from the agency. Before the recent COVID-19 papers, one of his most notable publications was a 2016 paper in The Lancet, which reported that extracting stem cells from the bone marrow of a person with end-stage heart failure and then reinjecting them could reduce the number of cardiac events that produced deaths or hospital admissions by 37%. The 126 patient, 31-site, phase II trial was billed in a press release, now not available on the University of Utah website but stored elsewhere, as the largest cell therapy trial for heart failure to date. Despite the apparent positive results, the sponsoring company Vericel no longer is developing stem cells for heart disease and, according to its webpage, is focused on advanced cell therapies for the sports medicine and severe burn care markets.

Patel left Miami under unclear circumstances, but has retained ties with Camillo Ricordi, an influential stem cell researcher at the University of Miami School of Medicine who is also the founder of a nonprofit called the Cure Alliance. The alliance previously focused on testing whether stem cells derived from umbilical cord blood could treat diabetes or Alzheimers, but has now pivoted to fighting COVID-19, according to its website. Ricordi is the principal investigator on a multisite trial to see whether the stem cells can treat lung inflammation in severe COVID-19 patients and Patel is listed in various references to the trial as a key contributor or coprincipal investigator. Ricordi did not reply to requests for comments on his relationship with Patel.

Patel recently tweeted that he is related to Dr. Desai by marriage but called that old news and added, Despite this I still do not have the information of what happened at Surgisphere. In addition to apparently connecting Mehra and Desai, Patel had prior connections with other authors of the NEJM paper and the preprint. David Grainger, co-author of the preprint, is a professor of biomedical engineering at the University of Utah and also works with Foldax. Grainger declined to comment.

Timothy Henry, a cardiovascular clinician and scientist at the Christ Hospital in Cincinnati and a co-author on the NEJM article, has written several scholarly articles with Patel, including the 2016 Lancet paper. Henry, who also declined to comment, advises Patels Triple-Gene, which develops cardiovascular gene therapy treatments. Henry and Patel adviseand Patel is a board member ofCreative Medical Technology Holdings, a Phoenix company that develops and markets stem cell therapies, including treatments purported to reverse aging and cure sexual disfunction.

Creative Medicals CaverStem and FemCelz kits are distributed to physicians who use them to extract stem cells from a patients bone marrow, then inject the cells into the penis or clitoral area to stimulate blood flow, according to a statement filed with the U.S. Securities and Exchange Commission. (As of the market close Friday, the publicly traded firms shares were valued at one-third of 1 cent.) The CaverStem treatments are advertised by the company as successful in more than 80% of patients, based on a 40-person phase I clinical trial that was not randomized or controlled, and on observations of 100 other patients. Phase I trials typically measure safety, not health benefits of a potential treatment.

Science contacted multiple colleagues or co-authors of Patel. None would comment. Before the retractions, two high-profile researchersDeepak Bhatt, who directs interventional cardiovascular programs at BWH; and Peter Gruber, a pediatric cardiothoracic surgeon at Yale Universityendorsed Patel on his LinkedIn page. Bhatt says he doesnt know Patel and attempted to remove his endorsement after being contacted by Science. Gruber says he overlapped with Patel at the University of Utah about a decade ago, but doesnt know his work in detail.

In contrast, Mehraauthor of more than 200 scholarly articles, editor of The Journal of Heart and Lung Transplantation, and head of the cardiology division of theUniversity of Maryland before moving to BWH in 2012enjoys considerable support even after the unraveling of the recent studies. Obviously, you dont rise to the position hes risen to without being ambitious, but Ive never had any indication whatsoever that he would do anything unethical, says Keith Aaronson, a cardiologist at the University of Michigan, Ann Arbor, who collaborated with Mehra on several studies, including a clinical trial of a mechanical pump for heart failure patients.

Mehra, the first author on both retracted papers, was the only one to issue a personal statement of apology, for failing to ensure that the data source was appropriate for this use. BWH and Harvard declined to say whether further investigation of Mehras roles in the papers would occur. (Mehra has written papers recently with another co-author of the Lancet paper, Frank Ruschitzka of University Hospital Zrich.)

I think he just fell into thisperhaps a little navely, says another former collaborator, cardiothoracic surgeon Daniel Goldstein of the Albert Einstein College of Medicine. Given the amount of data that was in the [Surgisphere] database, its just hard to believe someone would [fabricate] something like this.

Kassirer offers a harsher view: If youre a scientist and youre going to sign on to a project, by God you should know what the data are.

With reporting by Kelly Servick and John Travis.

This story was supported by theScienceFundforInvestigativeReporting.

Follow this link:
Who's to blame? These three scientists are at the heart of the Surgisphere COVID-19 scandal - Science Magazine

From stem cell treatments to electromagnetic field blocking patches, the FTC sent 35 more warning letters last week, putting the total ofletters at over 160.

In the natural products category, the FTC called foul on the following marketers that sell vitamins, supplements, silver, and Chinese herbal treatments:

The letters state that one or more of the efficacy claims made by the marketers are unsubstantiated because they are not supported by scientific evidence, and therefore violate the FTC Act. Recipients are advised to immediately stop making all claims that their products can treat or cure COVID-19, and to notify the FTC within 48 hours about the specific actions they have taken to address the agencys concerns.

FTC has sent out warning letters to manufacturers that make claims on social media, whether made directly by the company or endorsed by the company through a retweet on Twitter or a like on Facebook.

Because social media posts and claims fall under product labeling, retweets or likes are interpreted as a company endorsement under the Food, Drug and Cosmetic Act. The Act defines labeling as written, printed or graphic material accompanying a product.

In addition to the list of offenders above, the FTC also sent six other letters to multi-level marketing companies (MLMs) to remove and address unproven health and earnings claims. This is the second batch of warning letters sent to MLMs.

The companies claimed their products could treat or prevent coronavirus and/or made unsubstantiated claims regarding potential earnings that was messaged as a way to to recoup income lost due to the pandemic.

The FTC sent the letters to the companies listed below. The recipients are grouped based on the types of claims made.

Both Health and Earnings Claims:

Isagenix International LLC (Gilbert, Arizona)

The Juice Plus+ Company (Collierville, Tennessee)

Earnings Claims:

Melaleuca, Inc. (Idaho Falls, Idaho)

Health Claims:

Youngevity International, Inc. (Chula Vista, California)

Vivri USA, LLC (Dallas, Texas)

Plexus Worldwide, LLC (Scottsdale, Arizona)

The letters point out specific claims made on social media and videos posted online:

A Spanish-language social media post promoting Vivri USA, LLC that said, Take care of your health, your body, avoid many diseases many viruses, since this virus and many others are here to stay, coronavirus, influenza, flu, we should nourish our cells, our immune systems, reinforce it with the best nutrition system in the world

A social media post that said, #VIRUS_CORONA Worried? Ive been boosting my immune system for several years with high-quality Plexus supplements. You can too! #Plexus provides excellent all-natural supplements that truly work. Be sensible not fearful. Scientifically formulated & doctor-approved! Ask me!

A video promoting The Juice Plus Company that said,There are a lot of people out there who have lost income You may want to build a side income, you know, make $500 a month, $1,000 a month or more. Theres no ceiling on this. Its whatever you want it to be What would you like this do to for you? Maybe it could cover one of your bills, like a car payment. Or enjoy more time and financial freedom. I can tell you those are both possible at the same time because Ive been living that for the past eight years, and its wonderful to be able to offer that to other people.

Recipients are instructed to immediately cease making all unsubstantiated health claims and to notify the FTC within 48 hours about the specific actions they have taken to address the agencys concerns.

The letters also refer the companies to the agencys guidance for MLMs, noting that they are responsible for any claims made by their participants and representatives.

According to the latest consumer complaint data on its website, the FTC reported that so far there have been 64,236 overall complaints, $46.17 million in total fraud loss with $454 being the median fraud loss amount,

Originally posted here:
FTC ramps up enforcement with new wave of warning letters - NutraIngredients-usa.com

June 8, 2020

Teddy Hsieh, a rising junior at The University of Texas at Austin pursuing degrees in chemistry and electrical engineering, has been named to the 2020 Astronaut Scholar Class by theAstronaut Scholarship Foundation(ASF).

A national award given to a select group of outstanding undergraduate students studying in the fields of science, technology, engineering, or mathematics (STEM), the Astronaut Scholarship recognizes STEM majors with exemplary academic performance, ingenuity, and a unique aptitude for research.

As an Astronaut Scholar, Teddy will receive:

I am honored and humbled to receive this award, Teddy said. I know this honor could not have been possible without the dedication, guidance, and opportunities provided by UT staff and faculty. The mentorship I received here at UT exceeded all my expectations and empowered me to reach my goals.

Astronaut Scholarships are awarded to students in their junior or senior year of college who intend to pursue research or advance their field upon completion of their final degree.

Specifically, I strive to further the research field of nano-scale semiconductor fabrication with a focus on 3D optoelectronic materials, Teddy said of his future plans. At its essence, the field of nanoelectronics relies on a combination of chemically driven processes and electrical engineering design principles to fabricate materials necessary in high-performance devices, such as semiconductor lasers, solar cells, telecommunication systems, and computer processors.

This year, ASF awarded 56 scholarships to students from 41 universities across the country.

To learn more about the scholarship and how to apply, visit provost.utexas.edu/awards/astronaut.

View post:
UT Student Awarded Prestigious Astronaut Scholarship - UT News | The University of Texas at Austin

Submitted by Bloodworks Northwest

In the spirit of perseverance, sports teams Tacoma Rainiers, Tacoma Defiance, and OL Reign will host a Pop-Up Donor Center experience at their home field Cheney Stadium and ClubCorp will host a Pop-Up Donor Center at Canterwood Golf & Country Club. Additionally, Metro Parks Tacoma will provide support as both Pop-Ups combine to make the South Sound Pop-Up Donor Center from Monday, May 4 to Saturday, May 16, 2020.

The two Pop-Up blood donationlocations provide key areas for community members to give blood in the SouthSound. With COVID-19 social distancing recommendations, traditional blooddrives and bloodmobiles are temporarily unavailable further limitingopportunities to give blood. Bloodworks has turned to an innovative alternativewith Pop-Up Centers that are held in large venues, allowing higher level ofspace and safety for donors and staff. With current limitations to usage,Cheney Stadium and Canterwood Golf & Country Club will be utilized toprovide much needed support to the health and wellbeing of the South Soundcommunity.

Were thrilled to be partneringwith the South Sound sports community to ensure the local blood supply is readyto respond to the increased need for blood as hospitals prepare to resumeelective surgeries, said Bloodworks Northwest President & CEO Curt Bailey.The health of our community depends on donors making blood donation a regularhabit. Creating this opportunity for people to donate blood at Cheney Stadiumand Canterwood Golf & Country Club during this crucial time will help keepour community safe.

We R Tacoma is committed tosupporting the entire Puget Sound region, and during these difficult times areproud to provide Bloodworks NW our space in their efforts to mitigate theshortage of available blood in our region, said Tacoma Rainiers AssistantGeneral Manager Nick Cherniske. We hope the use of Cheney Stadium encouragesgreat participation as we come together for the greater community needs.

One of the many ways theSouth Sound community has been impacted by the COVID-19 crisis is the risk tothe supply of blood to Tacoma area hospitals, said Bill Predmore, CEO ofOL Reign. Bloodworks Northwest is doing tremendous work to address thischallenge. We are proud to support Bloodworks Northwest on this importantinitiative and encourage all supporters of OL Reign to donate if they are ableto do so.

People of all blood types are stillneeded every day to make an appointmentto give blood in support of cancer patients, trauma victims, premature babies, or totreat severely ill COVID-19 patients, among others. The unified effortby the teams, venues and organizations come at a crucial point when hospitalsproject the possibility of resuming elective surgeries. The increase in theneed for blood calls for an increase in donors to ensure a safe and stableblood supply.

Being involved in our community isa cornerstone of our mission at Canterwood Golf & Country Club, saidCanterwoood Golf & Country Club General Manager Tyler Hathaway. We aretruly grateful to have the opportunity to partner with Bloodworks to make sucha positive impact in so many lives during this very unique and uncertain time.

Many of us are looking fortangible ways we can help those whose lives are being upended on many frontsright now, said Shon Sylvia, Executive Director of Metro Parks Tacoma. Ifyoure in good health, we ask you to support the vital work of our partners atBloodworks by donating blood during this critical time of need.

Donors are urged to make theirone-hour donation appointmenttoday as a safe and essential action to support local patients. In accordancewith current social distancing guidelines, only scheduled appointments will beallowed and no walk-ins, guests, or people under age 16 are permitted onsite.On the day of their appointment, donors are invited to wear team gear as theysave a life and spread the word with #SouthSoundProud.

Also supporting the effort are 7Seas Brewing, Tims Cascade Snacks, Pepsi, and Sees Candies, which areproviding extra refreshments and perks for all donors at the South Sound Pop-UpDonor Center.

Bloodworks has posted informationaddressing questions and concerns for blood donors at bloodworksnw.org/coronavirus.Blood donation takes about an hour from registration to post-donationrefreshment. Information about who can donate andwhere, is available at http://www.bloodworksnw.org.

Canterwood Golf & Country Club Clubhouse 12606 54th Avenue NW Gig Harbor, WA 98332

Cheney Stadium Suites 2502 S Tyler St. Tacoma, WA 98405

May 4 May 16, 2020 Possibility of extension through the end of May

Sign-Up Link: https://schedule.bloodworksnw.org/DonorPortal/GroupLanding.aspx?s=494B

By appointment only

For the latest information on COVID-19 please visit theCDC website and Washington State Department of Health COVID-19 main page.

Appointments and information at BloodworksNW.org,800-398-7888, or text bloodapp to 91985 to receive a link on your phone. Pleasecheck website forextended donor center hours.

About Bloodworks Northwest Bloodworks Northwest isbacked by 75 years of Northwest history and 250,000 donors. It is local,nonprofit, independent, volunteer-supported and community-based. A recognizedleader in transfusion medicine, Bloodworks serves patients at hospitals in Washington,Oregon and Alaska partnering closely with local hospitals to deliver thehighest level of patient care. Comprehensive services include blood components,complex cross-matching, specialized lab services for organ transplants, carefor patients with blood disorders, and collection of cord blood stem cells forcancer treatment. Bloodworks Research Institute performs leading-edge researchin blood biology, transfusion medicine, blood storage and treatment of blooddisorders. Patients with traumatic injuries, undergoing surgeries or organtransplantation, or receiving treatment for cancer and blood disorders alldepend on our services, expertise, laboratories and research. Blood donationappointments can be scheduled at bloodworksnw.org.

AboutClubCorp Since its founding in 1957,Dallas-based ClubCorp has operated with the central purpose of BuildingRelationships and Enriching Lives. The leading owner-operator of private golfand country clubs, city and stadium clubs in North America, ClubCorp isrelentless in its pursuit of providing extraordinary experiences, meaningfulconnections, shared passions and memorable moments for its more than 430,000members. With approximately 20,000 peak-season employees and a portfolio ofover 200 owned or operated golf and country clubs, city clubs, sports clubs,and stadium clubs in 27 states, the District of Columbia and two foreigncountries, ClubCorp creates communities and a lifestyle through itschampionship golf courses, work spaces, handcrafted cuisine, resort-stylepools, tennis facilities, golf lounges, fitness centers and robust programming.

ClubCorpproperties include: Firestone Country Club (Akron, Ohio); Mission Hills CountryClub (Rancho Mirage, California); The Woodlands Country Club (The Woodlands,Texas); Capital Club Beijing; and The Metropolitan in Chicago. You can findClubCorp on Facebook at facebook.com/clubcorp and on Twitter at @ClubCorp.

Continued here:
South Sound Community Bands Together To Save Local Lives - southsoundtalk.com

Researchers at Pfizer Inc. and New York University are working on a never-before-tried coronavirus vaccine that the pharmaceutical company says could be available by September.

The vaccine, which carries genetic code known as messenger RNA, attempts to reprogram the deadly pathogen rather than manipulate the live virus.

"It is probably the fastest way of having a vaccine available to stem this pandemic, based on the data that I have seen," said Kathrin Jansen, who leads vaccine research for Pfizer.

Full coverage of the coronavirus outbreak

Let our news meet your inbox. The news and stories that matters, delivered weekday mornings.

The vaccine instructs a person's cells to make proteins associated with the coronavirus without making the person sick. Researchers hope the body's immune system will then kick in, creating the antibodies needed to fight off COVID-19.

"Messenger RNA is something the body produces on its own normally," said Mark Mulligan, chief of infectious diseases at NYU Langone Health. "It's kind of a new thing, but it's really not anything that's too different from what the body does for itself."

But Dr. Peter Hotez, co-director of the Texas Children's Center for Vaccine Development at Baylor University, said no RNA vaccine has been licensed because they have worked well only in laboratory animals.

"Those immune responses have not translated into ... good human immune responses," he said.

Download the NBC News app for full coverage of the coronavirus outbreak

Mulligan said he is optimistic about a trial underway at NYU, but he added that "the data will speak for itself."

"This is the science," he said. "You don't have to have faith or belief. The answer will come from the investigations that we do."

The vaccine is one of dozens under review in the global fight against the pandemic.

Tom Costello is an NBC News correspondent based in Washington, D.C.

Tim Stelloh is a reporter for NBC News, based in California.

See the rest here:
Pfizer, NYU working on innovative coronavirus vaccine that could be ready by end of summer - NBC News

The biopharma space has stepped up its efforts to both prevent and treat the coronavirus (SARS-CoV-2) that is threatening to bring the world to its knees.

A month is a very long time when it comes to infectious diseases. The first cases and deaths from the novel coronavirus (COVID-19) led to a response to contain the virus, but the difficulties of containment and the nature of international travel means cases and deaths have become global.

The latest statistics place the number of cases at 95,483 and deaths at 3,286 across 84 countries, though by the time you are reading this the number is likely to have skyrocketed.

So as the world tilters on the edge of a pandemic, we take a look at how industry is responding. There is no specific treatment for the virus, nor a vaccine, but a proactive response is seeing the pharma industry throw everything in its arsenal at attempting to stymie this global threat.

First off, vaccines. As the World Health Organization (WHO) states it can take a number of years for a new vaccine to be developed, it has not stopped companies and academia stepping up their R&D efforts.

Both Sanofi and J&J have separately teamed up with the US Department of Health and Human Services (HHS) to expediate vaccine development.

Sanofi Pasteur aims to reverse engineer proteins isolated from the virus to produce DNA sequences, which will then be mass produced using Sanofi Pasteurs baculoviral expression system and formulated into a vaccine that elicits an immune response. Well that is the aim.

Johnson & Johnsons unit Janssen Pharmaceutical, meanwhile, is reviewing products in development for Middle East Respiratory Syndrome (MERS) or Severe Acute Respiratory Syndrome (SARS), to identify promising candidates for the novel coronavirus, and aims to upscale production and manufacturing capacities, leveraging its AdVac and PER.C6 technologies.

Another Big Vaccine company, GlaxoSmithKline, has teamed with Chinese biotech Clover Biopharmaceuticals to help develop a preclinical protein-based vaccine candidate. GSK will provide its pandemic adjuvant system for further evaluation of Clovers S-Trimer, a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate produced using a mammalian cell-culture based expression system.

Inovio Pharmaceuticals has also entered the race, and like GSK has teamed up with a Chinese company. Together with Beijing Advaccine Biotechnology and a grant of up to $9 million from the Coalition for Epidemic Preparedness Innovations (CEPI), Inovio hopes to bring its DNA vaccine candidate INO-4800 rapidly into clinical trials. VGXI a subsidiary of GeneOne Life Science has been selected to manufacture the DNA vaccine from its facilities in The Woodlands, Texas.

Thegenome sequence for 2019-nCoVwas published on January 10, 2020, a VGXI spokesperson recently toldBioprocess Insider. This DNA sequence information is used by Inovio and their collaborators at the Wistar Institute to design a synthetic DNA plasmid for manufacturing at VGXI. No viral particles or proteins are involved in the manufacturing process. When delivered as a vaccine, the DNA plasmid can elicit a protective immune response.

RNA vaccines are also being investigated. Moderna Therapeutics recently shipped the first batch of its investigational messenger RNA vaccine mRNA-1273 to the National Institute of Allergy and Infectious Diseases (NIAID) for use in a Phase I study. The vaccine is designed to train the immune system to recognize cells invaded by the coronavirus.

Moderna also received a grant from CEPI, as has CureVac, which is looking to use its mRNA vaccine platform to expedite a candidate into trials. CureVacs technology and mRNA platform are especially suitable to rapidly provide a response to a viral outbreak situation like this, said CureVac CTO Mariola Fotin-Mleczek. Currently, we are in the process of developing a vaccine that, after successful preclinical tests, could be tested rapidly in humans in a clinical study.

But industry could be pipped to the clinical trial post by academia, with Israels MIGAL Research Institute claiming to be sitting on a human vaccine against COVID-19 as a by-product of a vaccine it has developed against avian coronavirus Infectious Bronchitis Virus (IBV).

From research conducted at MIGAL, it has been found that the poultry coronavirus has high genetic similarity to the human COVID-19, and that it uses the same infection mechanism, a fact that increases the likelihood of achieving an effective human vaccine in a very short period of time, the Institute says.

According to MIGALs Biotechnology group leader Chen Katz, the vaccine is based on a new protein expression vector, which forms and secretes a chimeric soluble protein that delivers the viral antigen into mucosal tissues by self-activated endocytosis a cellular process in which substances are brought into a cell by surrounding the material with cell membrane, forming a vesicle containing the ingested material causing the body to form antibodies against the virus.

Other pharma companies are looking to treat coronavirus, rather than prevent.

Regeneron has teamed with the HHS to use its VelociSuite technologies to identify and validation and develop preclinical candidates and bring them to development, having followed a similar approach to advance its investigational Ebola treatment REGN-EB3.

The tech platform includes the VelocImmune mouse technology, a genetically modified strain in which genes encoding mouse immune system proteins have been replaced by their human equivalents.

The life-saving results seen with our investigational Ebola therapy last year underscore the potential impact of Regenerons rapid response platform for addressing emerging outbreaks, said George Yancopoulos, Regeneron CSO. Our unique suite of technologies expedites and improves the drug discovery and development process at every stage, positioning Regeneron to respond quickly and effectively to new pathogens.

Meanwhile this week, Takeda announced it is looking to a therapy to target COVID-19 based on polyclonal hyperimmune globulin (H-IG). The candidate, TAK-888, aims to concentrate pathogen-specific antibodies from plasma collected from recovered patients. Initially, due to a lack of current donors, the firm will produce the therapy in a segregated area within its manufacturing facility in Georgia.

The Japan-headquartered firm will also review its current pipeline for any other viable candidates to take on COVID-19.

Such an approach has aided Gilead Sciences efforts. The firm has begun two Phase III clinical studies of its antiviral candidate remdesivir, developed (though never approved) to treat Ebola virus. It has also shown promise against other infectious diseases including Marburg, MERS and SARS.

This is an experimental medicine that has only been used in a small number of patients with COVID-19 to date, so Gilead does not have an appropriately robust understanding of the effect of this drug to warrant broad use at this time, Gilead said.

With about 1,000 patients set to be tested with remdesivir, Gilead has turned to a stockpile manufactured in response to Ebola to address present coronavirus needs, and in anticipation of expanded use is manufacturing two formulations of remdesivir, in both liquid and freeze-dried forms, while upping capacity and production internally and externally.

According to San Marinos Bioscience Institute SpA, a regenerative medicine center and stem cell production facility, mesenchymal stem cells could potentially be treatment for the novel coronavirus by improving lung microenvironment, inhibiting immune system overactivation, promoting tissue repair, protecting lung alveoli epithelial cells, preventing pulmonary fibrosis, and improving lung function.

The company, citing the Chinese open repository for scientific researchers chinaXiv.org , says at least 14 trials are taking place in China using stem cells to treat coronavirus patients after positive animal testing showed stem cells might be able to repair the severe organ damage caused by the virus.

The firm even reports that a critically ill 65-year-old Chinese woman infected with SARS-CoV-2, whose conditions significantly improved after the infusion of mesenchymal stem cells.

If mesenchymal stem cells do prove to be the solution to the potential coronavirus crisis, Bioscience Institute alludes to the advantage that they are obtained from fat cells.

That means that everyone can utilize his/her cells, eliminating any contamination or rejection risk, said Giuseppe Mucci, CEO of Bioscience Institute.

But expanding them to the quantity needed for infusion, that corresponds to at least 1 million cells per kg of weight, takes 2 to 3 weeks. That is why it is useful to cryopreserve a personal reserve of mesenchymal stem cells, that would allow to access an early, more successful, treatment.

Originally posted here:
How industry hopes to take on COVID-19 - Bioprocess Insider - BioProcess Insider

Dr. Meng-Lun Hsieh and Dr. Andrew Dean Shubin were married March 7 at the Warwick Melrose Hotel in Dallas. The Rev. Beth Dana, a Unitarian Universalist minister, officiated.

The bride, 33, who goes by Meng, is a fourth-year medical school student at Michigan State University, from which she also received a doctorate in biochemistry. She graduated from Williams College.

She is a daughter of Huey-Jen Liaw and Jyh-Cheng Hsieh of San Diego. The brides father is a research scientist at Sheatech, a biotech company in San Diego. Her mother, a stay-at-home parent, was a history teacher at Taibei High School, a private school in Taipei.

The groom, also 33, is a second-year general surgery resident at the University of Texas Southwestern Medical Center in Dallas. He graduated magna cum laude from the University of Washington, and received a doctorate in biomedical engineering from the University of Rochester, from which he also received a medical degree.

He is a son of Carol E. Shubin and Andy N. Shubin of Vancouver, Wash. His father retired as a photography teacher at Shahala Middle School in Vancouver. The grooms mother retired as a special-education teacher at Burton Elementary School in Vancouver.

The couple met a decade ago at the National Institutes of Health in Bethesda, Md., as post-baccalaureate research fellows, she focusing on a virus that infects bacteria, and he on skin stem cells. In April 2016, they met again at a conference for physician scientists in Chicago, and began dating long-distance.

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Meng Hsieh, Andrew Shubin - The New York Times