Cancer Drug Might Help Treat Alzheimer's

 A drug with a 30-year track record as an effective tool for fighting cancer may significantly improve memory and thinking in patients with mild-to-moderate Alzheimer's disease, new research suggests.

Sargramostim (brand name: Leukine) has long been used after cancer treatment to coax a patient's bone marrow to make more disease-fighting white blood cells. It uses a protein called GM-CSF that has been linked to a significantly lower risk of Alzheimer's among patients with rheumatoid arthritis (RA). RA patients typically have higher-than-normal levels of GM-CSF in their blood.

Working with 40 Alzheimer's patients, researchers have now concluded that a three-week regimen of sargramostim can actually reverse telltale brain damage associated with the disease, and markedly improve memory and thinking ability.

"This discovery of the safety and [effectiveness] of GM-CSF in Alzheimer's disease has the potential to be a breakthrough, which will be proved when a larger, longer trial is done to show that the benefits we saw are stronger and long lasting," said study lead author Huntington Potter. He's the director of the University of Colorado Alzheimer's and Cognition Center in Aurora.

The new findings come on the heels of another potential Alzheimer's breakthrough, in the form of an experimental drug called donanemab.

As reported March 13 in the New England Journal of Medicine, a monthly shot of donanemab for about 18 months effectively eliminated buildup of amyloid-beta plaques in the brains roughly 70% of Alzheimer's patients studied.

For the new study, 20 patients were treated with sargramostim five days a week for three weeks. Twenty other patients received placebo shots. The trial was double-blind, meaning neither the investigators nor participants knew which treatment they were getting.

At the end of the trial, those in the sargramostim group scored nearly 2 points higher on a standard 30-point test of thinking skills.

Their production of disease-fighting immune cells also shot up. And preexisting nervous system damage — including levels of amyloid plaque and Alzheimer's-related tangles in the brain — all reversed, in what researchers described as a "partial normalization" process.

The study showed the benefits induced by GM-CSF were found to last as much as 45 days after treatment ended, Potter noted. The drug was also found to be safe and well-tolerated.

Researchers have approval from the U.S. Food and Drug Administration and funding from the U.S. National Institutes of Health and the Alzheimer's Association to carry out a longer, larger trial of GM-CSF to verify their findings.

Heather Snyder, vice president of medical and scientific relations for the Alzheimer's Association, called the research into use of anti-inflammatory drugs in dementia treatment "intriguing."

"The Alzheimer's Association is actively investing in clinical trials to explore their potential use for dementia treatment," she said.

At the same time, Snyder cautioned that this line of research is still "very preliminary" and work must continue in larger, more diverse populations.

"Alzheimer's is complex, and successful treatment will most likely address the disease in multiple ways with medication and behavior interventions, like combination therapies similar to heart disease and cancer," she said. "We must accelerate the pursuit of a wide variety of Alzheimer's treatments with the idea that they will likely be used in combination to be most effective."

Snyder said the association is funding and collaborating with scientists around the world to make this happen.

Potter's team reported its findings March 25 in the online edition of the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions.

https://www.newsmax.com/health/health-news/cancer-dug-alzheimers-treatment/2021/03/26/id/1015265/

Vaccine skeptics lured to shots with gift cards, hotel discounts

 In the global effort to encourage skeptics to get vaccinated against Covid-19, one insurer hopes gift cards and cheaper hotel stays may help tip the balance.

Manulife Financial Corp. is adding the vaccination as a way to win points in its Vitality health-tracking program, which rewards health- and life-insurance policyholders for things such as exercising, getting health screenings or taking nutrition classes online. Those points can be redeemed for rewards including Amazon.com Inc. gift cards, Hotels.com lodging discounts and less-expensive gym memberships.

Canadians who upload a proof of vaccination will receive 400 points, comparable to what they’d earn from 40 light workouts, said Manulife Canada Chief Executive Officer Mike Doughty. Adding vaccinations to the Manulife Vitality rewards program, which has more than a million members, is a way for the company to encourage people to get the shots without putting too much pressure on them, he said.

“When you think about the importance of vaccination in terms of protecting yourself from getting seriously ill, or worse, from Covid, it makes great sense for us to include it in the program,” Doughty said in an interview. “It doesn’t force anyone to make a decision, but it certainly encourages and rewards them for making that decision.”

The company is rolling out a similar program through its John Hancock Vitality program in the U.S.

https://www.bloomberg.com/news/articles/2021-03-23/vaccine-skeptics-lured-to-shots-with-gift-cards-hotel-discounts

Paging Dr. Hayek

 Free-market advocates have responded to the Covid-19 pandemic relatively quietly. They should speak up. The pandemic and its fallout show the virtues of market forces while revealing the dangers of relying on bureaucratic central planners and shortsighted regulations.

An opposition to central planning grounded in the understanding that we can’t predict the future, a healthy skepticism of bureaucrats and experts who fancy themselves philosopher-kings, an awareness of the dangers of outdated and unnecessary regulations: these are the tenets of free-market thinking as espoused by the patron saint of libertarians, Friedrich Hayek. America’s response to Covid-19 reinforces their wisdom, and conservatives should take note.

The tension between adaptive individuals and misguided experts was on display in the pandemic’s early months. In February 2020, Surgeon General Jerome Adams was one of many public-health experts who discouraged Americans from wearing masks, asserting: “They are NOT effective in preventing [the] general public from catching” Covid-19. Yet common sense dictates that masks keep things off your face. It makes sense that a worried citizenry, faced with a microscopic foe, would take to wearing masks. It also makes sense that public-health experts like Adams wanted to preserve the supply of N95 masks for health-care providers. He could have said as much: “You can wear a kerchief if you want, but please leave the heavy-duty masks to the frontline workers.” Instead, public-health experts insisted that masks were ineffective, then revised their position, and have since called for double masking.

When experts invoke their status to coerce people into ignoring common sense and embracing counterintuitive positions (“masks don’t help,” “suspending international travel won’t slow transmission”), they slip from expertise into manipulation. That’s why, to many people, masking is no longer a question of knowledge versus ignorance; it’s a question of belief.

Experts are nothing without regulations, many of which arrested the country’s early pandemic response. As early as May 2020, the New York Times reported that “existing regulations and red tape . . . impeded the rapid rollout of testing nationally.” The CDC and FDA ordered researchers at the Washington State Department of Health who wanted to begin testing for Covid-19 in January 2020 to stop. The reason? They were not operating in certified “clinical” laboratories, and the FDA had not approved their Covid test. That they were credentialed doctors conducting an ongoing flu study was not enough to appease state officials. Meantime, the CDC struggled to roll out a test of its own as the FDA dragged its feet on approving privately manufactured tests. The CDC finally released its tests two months later, only to recall them shortly thereafter when labs around the country found them inaccurate. The FDA concluded that the CDC repeatedly violated its own quality protocols, as researchers moved between labs without changing their coats and assembled test components in the same rooms where people were handling virus samples. Seven months after the recall, it was reported that CDC officials knew the tests were faulty, but chose to release them anyway.

One struggles to identify the worst aspect of this saga. Is it that federal agencies stymied efforts to test and trace the coronavirus, or that bureaucrats in Washington, D.C. exert such control over doctors in Washington State? Perhaps it’s that federal agencies commanded the rest of the country to “leave it to the experts,” only to deliver too little, too late. Fortunately, the government left a crucial part of the pandemic response to the private sector. The rapid development of effective vaccines shows what happens when the state doesn’t interfere unduly in private affairs.

To its credit, the FDA helped drug companies move quickly through the agency’s burdensome approval process. It allowed emergency use of remdesivir, Gilead’s antiretroviral, which has proved effective in mitigating Covid-19 symptoms. The FDA does not frequently grant “emergency use authorizations,” which let drugmakers sidestep the traditional approval process and give patients access to unapproved drugs shown to be effective in treating a disease.

The FDA also expedited the review of the Pfizer and Moderna vaccines, demonstrating a swiftness that would have previously seemed impossible for the notoriously sluggish agency. Moderna’s vaccine went from the lab to clinical trials in a record 69 days. That’s because the FDA allowed the companies to move through all three phases of clinical trials simultaneously, rather than sequentially. This process ordinarily takes around six years, and experts who believe the process is overly cautious have frequently criticized it.

The government did partner with drug companies through Operation Warp Speed, but more important is what it didn’t do. It didn’t impose new regulations or try to seize drug companies’ patents, it didn’t hold hearings on drug prices, and it didn’t interfere with the FDA’s expedited approval processes. It didn’t penalize Pfizer for not taking government money. It simply let the companies do what they do best. Left to their own devices, Sanofi and Novartis agreed to help produce the Pfizer vaccine in their facilities—refuting a common refrain among would-be regulators that drug companies act only out of self-interest and never for the common good. Now, about a year since the pandemic began, we have three viable vaccines and more on the way.

If vaccine manufacturing shows the potential in private industry, vaccine distribution shows the importance of private individuals. So far, it’s been a mixed bag. The country is administering about 2 million vaccines per day, an inoculation rate that has some experts predicting a return to normalcy by summer. But distribution has been stymied by everything from technical problems to unprecedented weather events.

No matter how much we prepare, we will always face what Hayek called the knowledge problem: the dispersal of “incomplete and frequently contradictory” information among individuals in a complex society that renders top-down planning inefficient. To the extent that we can solve it, the solution lies not in a denser central plan but in trusting the actions of individuals.

Consider just a few of the enterprising Americans who have filled the gaps in vaccine-distribution plans. Hugh Ma, a software engineer, built a site that tracks available vaccine appointments in New York City for just $50 after he struggled to get his mother an appointment. His site, TurboVax, collects information from multiple databases and posts appointment availability to Twitter in real time. Said Ma: “This wasn’t a priority for governments, which was unfortunate. But everyone has a role to play in the pandemic, and I’m just doing the very little that I can to make it a little bit easier.” Jerry Walkowiak, a Chick-fil-A manager in Mount Pleasant, South Carolina, helped eliminate the backlog at a local drive-thru vaccine center at the behest of the town’s mayor. After identifying the problem, Walkowiak reorganized the system and reduced an hours-long wait to just 15 minutes. More than 1,000 people received their vaccine in a single day, thanks to Walkowiak’s efforts.

The point here is not that Chick-fil-A should take over the government. It’s that the government isn’t infallible, and that the bureaucracy often delays and distorts otherwise helpful initiatives. Even when top-down solutions are necessary, individual and local action can play an invaluable role.

Considering the many examples over the past year of the weaknesses of government, one would suspect that we would emerge from the pandemic with a new appreciation for limited government and free markets. Instead, a majority of liberals and some conservatives have soured on capitalism and begun calling for a more robust, interventionist federal state. If these trends continue, we may soon find that the real era of big government is yet to come.

The federal government and state governments alike have poured time, money, and manpower into fighting the coronavirus—often admirably, and sometimes successfully. But on balance, the government response to Covid reminds us that government is too often the problem, not the solution. This was true nearly a century ago, when Hayek warned of the problems with central planning in The Road to Serfdom, and it’s true now. Our pandemic response depended on liberty; so, too, does our future.

Tim Rice is an associate editor of the Washington Free Beacon.

https://www.city-journal.org/hayek-covid-19-lessons

Mapping COVID risk in urban areas: a way to keep the economy open

 As COVID-19 vaccines slowly roll out across the world, government officials in densely populated countries must still manage vulnerable communities at highest risk of an outbreak.

In a new study published in the Journal Risk Analysis, researchers in India propose a COVID Risk Assessment and Mapping (CRAM) framework that results in a zoned map that officials can use to place more targeted restrictions on high-risk communities. Successfully used by officials in Jaipur at the peak of the pandemic last spring, their framework could help other vulnerable countries avoid a shutdown of their regional economies.

Led by Shruti Kanga, associate professor in the Centre for Climate Change and Water Research at Suresh Gyan Vihar University, the team used satellite remote sensing and Geographic Information Systems (GIS) technology to conduct a spatial risk assessment of the city of Jaipur, located in the state of Rajashthan.

Jaipur had been experiencing a rapid increase in COVID-19 cases since the first cases of the virus were diagnosed in India in January 2020. Due to its high population density, the Jaipur area was subject to extended lockdowns. "It became imperative for the authorities to manage lockdowns without affecting the state's economy," the authors write.

The researchers developed CRAM to provide officials with a vulnerability assessment-based lockdown strategy. Their risk-mapping method involves three steps: 1. Generating GIS layers of administrative, hazard, socio-economic, and bio-physical data. 2. Integrating hazard and vulnerability to generate risk assessment. 3. Risk mapping using an area's "boundary zones" for prioritizing risk areas and leading to prompt action. The final result is a GIS map of an area with color-coded risk zones delineating the neighborhoods at highest risk of a COVID outbreak.

CRAM generates a risk assessment by integrating hazard and vulnerability components associated with COVID. In the case of Jaipur, this data included these vulnerability risks: total population, population density, and availability of clean water for sanitation. Hazard risks included proximity to COVID "hotspots" (areas with a high density of confirmed positive cases) and land use/land cover--pinpointing high risk settlements and agriculture, where people gather and get exposed to the virus.

Data for each of these factors were used to create a GIS layer for the final map. GIS gives researchers the ability to layer unrelated data points on top of one another to reveal trends via visual maps. "Pandemics are a spatial phenomenon," says Suraj Kumar Singh, a co-author and professor in the Centre for Sustainable Development at Suresh Gyan Vihar University. "Their spread and lethality can only be understood holistically using GIS tools."

The researchers established five levels of "risk" zones: red, orange, blue, green, and pink (from highest to lowest risk). The level of risk was determined by multiplying hazard by vulnerability. The resulting color-coded map for Jaipur depicted significant spatial variation -- indicating that most areas under high-risk red and orange zones were concentrated along the northeastern and southwestern zones of the study area.

After consulting with authorities managing COVID-19 in the area, the researchers listed specific guidelines for the areas under each risk category. For example, closing shops in red zones; allowing shops to be open three days a week in blue zones; and allowing shops to be open five days a week in green zones. "In Jaipur, our CRAM helped local authorities in deciding which areas to put under lockdown," says Singh.

Highly populated countries of Asia--India, Bangladesh, and Pakistan-- have been especially vulnerable to COVID-19 because of their poverty, population densities, and weak health care systems. Some parts of India are currently experiencing a second wave of COVID-19, including the state of Maharashtra, home to the bustling city of Mumbai. Singh suggests that the CRAM framework could be used in any densely populated area with high-risk communities.

"The CRAM framework can be applied anywhere in the world," says Singh. "Researchers and decision-makers only need to change the parameters that are specific to that particular geographic region governing COVID-19 or any pandemic."

https://www.eurekalert.org/pub_releases/2021-03/sfra-mcr032621.php

How COVID-19 affects the brain

 Maura Boldrini, MD, PhD^1,2; Peter D. Canoll, MD, PhD³; Robyn S. Klein, MD, PhD^4,5,6

doi:10.1001/jamapsychiatry.2021.0500

COVID-19 has resulted in more than 120 million cases and 2.6 million deaths to date. Respiratory and gastrointestinal symptoms are accompanied by short- and long-term neuropsychiatric symptoms (NPs) and long-term brain sequelae.

Some patients present with anosmia, cognitive and attention deficits (ie, brain fog), new-onset anxiety, depression, psychosis, seizures, and even suicidal behavior.^1,2 These present before, during, and after respiratory symptoms and are unrelated to respiratory insufficiency,¹ suggesting independent brain damage. Follow-ups conducted in Germany and the United Kingdom found post–COVID-19 NPs in 20% to 70% of patients, even in young adults, and lasting months after respiratory symptoms resolved,¹ suggesting brain involvement persists.

Entering through angiotensin-converting enzyme 2 receptors,² SARS-CoV-2 can damage endothelial cells leading to inflammation, thrombi, and brain damage. Moreover, systemic inflammation leads to decreased monoamines and trophic factors and activation of microglia, resulting in increased glutamate and N-methyl-d-aspartate (NMDA)³ and excitotoxicity (Figure). These insults induce new-onset or re-exacerbation of preexisting NPs.

Figure.  Brain Vascular Injury, Neurotransmitter System Dysfunction, Thrombotic Events, Neuronal Damage, and Neuropsychiatric Symptoms

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A, SARS-CoV-2 invades endothelial cells via transmembrane angiotensin-converting enzyme 2 (ACE2) receptor, enabled by transmembrane protease, serine 2 (TMPRSS2). B, Cytokine elevation and microglia activation result in increased kynurenine, quinolinic acid, and glutamate, and neurotransmitter depletion. C, Coagulation cascade and elevation of von Willebrand factor (vWF) lead to thrombotic events. D, Altered neurotransmission, excitotoxicity by increased glutamate, and hypoxic injury contribute to neuronal dysfunction and loss. E, Neuropsychiatric symptoms differ depending on the Brodmann area involved. IL indicates interleukin; NMDA, N-methyl-d-aspartate; TNF, tumor necrosis factor.

Does the Virus Invade the Brain?

SARS-CoV-2 is known to penetrate the olfactory mucosa, causing loss of smell, and may enter the brain, migrating from the cribriform plate along the olfactory tract² or through vagal or trigeminal pathways; however, definitive evidence for this is lacking. SARS-CoV-2 could pass the blood-brain barrier (BBB) because inflammatory cytokines induce BBB instability or via monocytes.⁴ It could reach brain tissue via circumventricular organs (CVOs), midline structures around the third and fourth ventricles, that monitor blood and cerebral spinal fluid content via fenestrated capillaries lacking the junctional proteins expressed in the BBB. Viral RNA was detected by reverse transcription–quantitative real-time polymerase chain reaction but not by in situ hybridization in medulla and cerebellum,² located next to the area postrema, a CVO that controls emetic responses to toxins. SARS-CoV-2 protein has been found in brain vascular endothelium but not in neurons or glia.² Thus, detected viral RNA may represent contamination by vasculature in leptomeninges and Virchow-Robin spaces. Histopathologic analysis of whole human brain showed microglial nodules and phagocytosis of neurons (neuronophagia) in brain stem and less frequently in cortex and limbic structures, associated with sparse lymphocytic infiltration, and no correlations between histopathologic findings and levels of viral messenger RNA in the same brain.⁵ While ageusia, nausea, and vomiting may be related to CVO and brain stem viral invasion, other short-term and long-lasting NPs are more likely due to neuroinflammation and hypoxic injury. Brain stem involvement may explain persistent autonomic abnormalities and anxiety.

Cytokines and Microglia Activation Lead to Neurotoxicity

Patients with severe COVID-19 infection have been reported to experience a severe cytokine storm, with increased serum levels of proinflammatory cytokines including interleukin (IL) 1, IL-6, IL-10, and tumor necrosis factor (TNF)-α. TNF-α can directly cross the BBB by transport (increased BBB permeability due to cytokine-induced damage)⁴ or CVOs. Once across the BBB, cytokines activate microglia and astrocytes.⁶ In addition to phagocytosing damaged cells, activated microglia secrete inflammatory mediators, including glutamate, quinolinic acid, ILs, complement proteins, and TNF-α.⁷ Increased quinolinic acid results in higher glutamate and upregulation of NMDA receptors, possibly inducing altered learning, memory, neuroplasticity, hallucinations, and nightmares. Excitotoxicity and neuronal loss result in region- and neurotransmitter-specific NPs.

Inflammation and NPs

Increased inflammation activates the enzyme indoleamine dioxygenase, which metabolizes tryptophan to kynurenine rather than serotonin.³ Reduced neurotransmitter release was demonstrated in patients treated with interferon alfa who exhibited increased positron emission tomography fluorodopa ¹⁸F uptake and decreased turnover in caudate and putamen, which correlated with depression and fatigue severity. Similarly, interferon- or IL-based immunotherapy can induce depression. Inflammation leads to blunted monoamine neurotransmission, anhedonia, negative cognitive, psychomotor and neurovegetative symptoms, depression, and suicidal behavior, which poorly respond to conventional antidepressants.³ In individuals who attempt suicide and have major depressive disorder, studies found elevated plasma kynurenine, high IL-1 and IL-6 levels in blood, cerebral spinal fluid, and brain, and increased serum C-reactive protein correlating with brain glutamate levels. TNF-α and IL-6 levels may predict negative and depressive symptoms in people at risk of psychosis, and higher IL-6 correlates with smaller hippocampus volume. Elevated IL-1β signaling decreases hippocampal neurogenesis and increases apoptosis in mammals. Suicide decedents with major depressive disorder have increased proinflammatory and decreased neurogenesis markers in postmortem hippocampus,⁸ together with smaller dentate gyrus, fewer granule neurons, and neural progenitor cells.⁹ Therefore, neuroinflammation may contribute to the pathogenesis of NPs reducing neurotransmitters and neurotrophins and increasing excitotoxicity.³

Interplay of Inflammation and Coagulation

Virus entrance into endothelial cells of brain vasculature activates neutrophils, macrophages, thrombin production, and complement pathways, promoting microthrombi deposition.² COVID-19 brain damage shows macro– and micro–hypoxic/ischemic injury and infarcts at autopsy.⁵ Moreover, the complement cascade mediates synaptic pruning by microglia following viral infections.⁷ Therefore, NPs of COVID-19 could result from microstrokes and neuronal damage, and symptoms consequently differ depending on the brain region involved. Mechanisms of COVID-19 brain damage may resemble those involved in traumatic brain injury, where a combination of proinflammatory status and microvascular injury resulting in neuronal loss have been implicated in the pathogenesis of suicidal behavior.¹⁰ Conversely, a successful clinical outcome would result from an initial immune response involving toll receptors and blunted nonpriming or low-priming delayed inflammation.

Understanding cellular and molecular aspects of COVID-19 brain damage could direct interventions to reduce long-term NPs. Interventions may involve antagonists of cytokines (etanercept, infliximab), NMDA receptor (ketamine), TNF-α and anti-inflammatory pathways (aspirin, celecoxib), and kynurenine pathway modulators (minocycline).³ Mitigating long-term post–COVID-19 cognitive, emotional, and behavioral sequelae would decrease disease burden. COVID-19 neuropathology may serve as a model for deciphering neurodegenerative processes related to neuroinflammation in other brain diseases and developing new treatment strategies.

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2778090

Cancer drug cuts toxicity of protein from COVID-19 virus

 University of Maryland School of Medicine (UMSOM) researchers have identified the most toxic proteins made by SARS-COV-2--the virus that causes COVID-19 - and then used an FDA-approved cancer drug to blunt the viral protein's detrimental effects. In their experiments in fruit flies and human cell lines, the team discovered the cell process that the virus hijacks, illuminating new potential candidate drugs that could be tested for treating severe COVID-19 disease patients. Their findings were published in two studies simultaneously on March XX in Cell & Bioscience, a Springer Nature journal.

"Our work suggests there is a way to prevent SARS-COV-2 from injuring the body's tissues and doing extensive damage," says senior author of the study Zhe "Zion" Han, PhD, Associate Professor of Medicine and Director of the Center for Precision Disease Modeling at UMSOM. He notes that the most effective drug against Covid-19, remdesivir, only prevents the virus from making more copies of itself, but it does not protect already infected cells from damage caused by the viral proteins.

Prior to the pandemic, Dr. Han had been using fruit flies as a model to study other viruses, such as HIV and Zika. He says his research group shifted gears in February 2020 to study SARS-COV-2 when it was clear that the pandemic was going to significantly impact the U.S.

SARS-COV-2 infects cells and hijacks them into making proteins from each of its 27 genes. Dr. Han's team introduced each of these 27 SARS-CoV-2 genes in human cells and examined their toxicity. They also generated 12 fruit fly lines to express SARS-CoV-2 proteins likely to cause toxicity based on their structure and predicted function.

The researchers found that a viral protein, known as Orf6, was the most toxic killing about half of the human cells. Two other proteins (Nsp6 and Orf7a) also proved toxic, killing about 30-40 percent of the human cells. Fruit flies that made any one of these three toxic viral proteins in their bodies were less likely to survive to adulthood. Those fruit flies that did live had problems like fewer branches in their lungs or fewer energy-generating power factories in their muscle cells.

For the remaining experiments, the researchers focused on just the most toxic viral protein, so they could figure out what cell process the virus hijacks during infection. Dr. Han's team found that the virus' toxic Orf6 protein sticks to multiple human proteins that have the job of moving materials out of the cell's nucleus--the place in the cell that holds the genome, or the instructions for life.

They then discovered that one of these human moving proteins, targeted by the virus, gets blocked by the cancer drug selinexor. The researchers tested selinexor on human cells and fruit flies making the toxic viral protein to see if the drug could help reverse the damage. Selinexor, like many cancer drugs is itself toxic. However, after accounting for its toxic effects, the drug improved human cell survival by about 12 percent. Selinexor prevented early death in about 15 percent of the flies making the toxic viral protein. The drug also restored branches in the lungs and the energy-generators in the muscle cells. Selinexor is FDA-approved to treat certain blood cancers.

"More than 1,000 FDA-approved drugs are in clinical trials to test as treatments for Covid-19, and luckily a trial testing selinexor, the drug used in our study, is being performed already," says Dr. Han. "If this trial proves to be successful, our data will have demonstrated the underlying mechanism for why the drug works."

Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, commented, "Although we now have vaccines, it may still be a while before we will have Covid-19 infections under control, especially with the new variants emerging. We will need to tap into every tool in the arsenal available to protect people from needless sickness, disability or even death, and this study guides us towards a new target for potential therapeutics."

###

These two studies were funded by a University of Maryland COVID-19 Accelerated Translational Incubator Pilot Grant, the University of Maryland, the Baltimore Institute for Clinical and Translational Research, and the University of Maryland School of Pharmacy Mass Spectrometry Center.

The researchers do not have any conflicts of interest to report.

https://www.eurekalert.org/pub_releases/2021-03/uoms-cdl032621.php

Preservative used in many processed foods may harm immune system

 A food preservative used to prolong the shelf life of Pop-Tarts, Rice Krispies Treats, Cheez-Its and almost 1,250 other popular processed foods may harm the immune system, according to a new peer-reviewed study by Environmental Working Group.

For the study, published this week in the International Journal of Environmental Research and Public Health, EWG researchers used data from the Environmental Protection Agency's Toxicity Forecaster, or ToxCast, to assess the health hazards of the most common chemicals added to food, as well as the "forever chemicals" known as PFAS, which can migrate to food from packaging.

EWG's analysis of ToxCast data showed that the preservative tert-butylhydroquinone, or TBHQ, has been found to harm the immune system both in both animal tests and in non-animal tests known as high-throughput in vitro toxicology testing. This finding is of particular concern during the coronavirus pandemic.

"The pandemic has focused public and scientific attention on environmental factors that can impact the immune system," said Olga Naidenko, Ph.D., EWG vice president for science investigations and lead author of the new study. "Before the pandemic, chemicals that may harm the immune system's defense against infection or cancer did not receive sufficient attention from public health agencies. To protect public health, this must change."

TBHQ

TBHQ is a preservative that is pervasive in processed foods. It has been used in foods for many decades and serves no function besides increasing a product's shelf life. Using new non-animal test results from ToxCast, EWG found that TBHQ affected immune cell proteins at doses similar to those that cause harm in traditional studies. Earlier studies have found that TBHQ might influence how well flu vaccines work and may be linked to a rise in food allergies.

PFAS

Using ToxCast, EWG analyzed all publicly available studies that show how PFAS migrate to food from packaging materials or processing equipment. This is the first known compilation of available research on PFAS migration from packaging to food. In 2017, nationwide tests showed that many fast-food chains used food wrappers, bags and boxes coated with highly fluorinated chemicals.

Human epidemiological studies show that PFAS suppresses immune function and decreases vaccine efficacy. Recently published research has also found a link between high levels of PFAS in the blood and the severity of Covid-19.

Surprisingly, for most PFAS, the ToxCast results did not match previous animal and human test data. This illustrates the limitations of this new chemical testing method. More research is needed to understand how PFAS harm the immune system.

Food Chemicals Regulation

The Food and Drug Administration's approach to the regulation of food additives does not consider the latest science on the health harms of additives that may be legally added to processed foods manufactured in the U.S. Last year, EWG published Food Additives State of the Science, which highlighted additives known to increase the risk of cancer, harm the nervous system and disrupt the body's hormonal balance.

Chemicals linked to health harms can be legally added to packaged foods because the FDA frequently allows food manufacturers to determine which chemicals are safe. Additives like TBHQ were approved by the FDA decades ago, and the agency does not consider new science to reassess the safety of food chemicals.

"Food manufacturers have no incentive to change their formulas," said Scott Faber, senior vice president for government affairs at EWG. "Too often, the FDA allows the food and chemical industry to determine which ingredients are safe for consumption. Our research shows how important it is that the FDA take a second look at these ingredients and test all food chemicals for safety."

Less Toxic Food Preservatives

Processed foods can be made without these potentially harmful ingredients, so shoppers should read labels carefully. TBHQ is often, though not always, listed on the ingredient label. It will be listed if it has been added to the product during manufacturing. But it can also be used in food packaging, particularly plastic packaging, in which case it may migrate to food.

EWG's Food Scores database helps consumers find products made with healthier alternatives, and our Healthy Living app allows shoppers to scan products while in stores to choose a better option.

EWG recommends that immunotoxicity testing be prioritized for chemicals in food and food contact materials in order to protect public health from their potential harm to the immune system.

EWG also calls on the FDA to close the regulatory loophole that allows potentially unsafe food additives to remain on the market. The FDA should also promptly review additives like TBHQ to reflect new science.

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More information: Olga V. Naidenko et al. Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food, International Journal of Environmental Research and Public Health (2021). DOI: 10.3390/ijerph18073332

https://medicalxpress.com/news/2021-03-pop-tarts-hundreds-popular-foods-immune.html