Likely link between mitochondrial dysfunction and age-dependent cognitive disorders

 Increased oxidative damage is linked to neurodegenerative disorders such as Alzheimer's disease (AD). Even though the pathophysiology of AD has been widely investigated, the likely relationship between mitochondrial dysfunction and the disease remains largely unknown. A research team led by Prof. Koji Fukui from Japan's Shibaura Institute of Technology has confirmed that AD progression is linked to oxidative brain damage, which impairs cognitive function in AD transgenic mice in an age-dependent manner.

The mitochondrial electron transport chain, which is required for generating energy during cellular processes, also produces reactive oxygen species (ROS) that attack tissue and cause oxidative damage. This damage can cause mitochondrial dysfunction and even lead to cell death. Since our brain uses more oxygen than other organs, it is more vulnerable to this ROS damage.

According to literature, ROS also causes the buildup of amyloid-β (Aβ), which marks the onset of Alzheimer's disease (AD), a serious irreversible neurodegenerative disorder. Treatments for AD do not stop its progression, necessitating the development of new therapeutics.

In a prior study, a team of scientists found that oxidation levels were substantially higher in older rats with vitamin E deficiency than in younger rats. Furthermore, ROS production via mitochondrial oxidation could damage brain cells, implying a strong link between AD and mitochondrial dysfunction. To improve this understanding, the same group of scientists has now demonstrated that the progression of AD is closely associated with oxidative brain damage. The study, led by Prof. Koji Fukui, along with his colleagues Mr Naoki Yoshida, Mr. Yugo Kato, and Prof. Hirokatsu Takatsu, was recently published in Biomedicines. "We showed that oxidation negatively impacted the mitochondria which led to cognitive dysfunction," explains Prof. Fukui, who is the corresponding author of the study.

The scientists used three groups of AD mice aged 3, 6, and 20 months, along with healthy controls. For testing their cognitive and coordination abilities, the mice were examined in two well-known experiments: the Morris water maze and the Rota-rod test. They discovered that the AD mice took longer to complete their maze goals but did not slow down. In the Rota-rod test, the 6- and 20-month-old AD mice stayed on the rod for a longer time, while the age-matched control mice fell quicker. Prof. Fukui explains, "The difference in fall time could be attributed to the weight difference between the two groups, as the control mice were heavier than the AD mice." These results suggested that AD mice were cognitively impaired but did not have any coordination issues.

To identify which AD-related proteins were responsible for such cognitive impairment, the authors collected tissue samples from various parts of the brain from both groups of mice and assessed the levels of oxidative markers in the samples. First, they found that AD mice had higher levels of Aβ, with a gradual increase observed with age. To their surprise, the AD-related protein Aβ1-42 was significantly higher in the hippocampus than in other parts of the brain. However, they did not find any alterations in the levels of the tau protein, which is another marker that accumulates in AD pathology. Overall, it was confirmed that Aβ1-42 aggregation in the hippocampus caused cognitive impairment in AD mice.

The team also had speculations about ROS-induced mitochondrial damage being closely related to neuron survival. To validate their hypothesis, they determined the levels of some key mitochondrial oxidative enzymes, including nicotinamide-nucleotide adenylyltransferase (NMNAT)-3, which exhibits anti-ageing effects. While NMNAT-3 was found to be lowered, levels of 3-NT (3-nitrotyrosine), an indicator of higher oxidation, increased with age in AD mice. "With reduced levels of NMNAT-3 and higher levels of 3-NT, it is evident that oxidation causes mitochondrial dysfunction, and eventually leads to cognitive dysfunction," comments Prof. Fukui.

The team is optimistic about the potential implications of their results, particularly in increasing the intake of antioxidant compounds that can help our bodies mitigate ROS. In fact, many natural antioxidants, such as vitamins E and C, can be obtained from dietary sources. Prof. Fukui concludes by surmising, "If mitochondria can be protected from ROS, mitochondrial function and cognitive function may be maintained. Future research should concentrate on developing diagnostic markers to detect early alterations in the brain, as well as exploring compounds with high antioxidant activity in mitochondria."

Story Source:

Materials provided by Shibaura Institute of Technology. Note: Content may be edited for style and length.

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Journal Reference:

1. Naoki Yoshida, Yugo Kato, Hirokatsu Takatsu, Koji Fukui. Relationship between Cognitive Dysfunction and Age-Related Variability in Oxidative Markers in Isolated Mitochondria of Alzheimer’s Disease Transgenic Mouse Brains. Biomedicines, 2022; 10 (2): 281 DOI: 10.3390/biomedicines10020281

https://www.sciencedaily.com/releases/2022/02/220214095824.htm

'Amazing' nanoparticles from maize: A potent and economical anti-cancer therapeutic

 Nanoparticles, or particles whose size varies between 1 and 100 nanometers, have shown tremendous potential in many areas of science and technology, including therapeutics. However, conventional, synthetic nanoparticles are complicated and expensive to produce. Extracellular vesicles (EVs), which have emerged as an alternative option to synthetic nanoparticles, show challenges for mass production.

Another recently emerging option is that of plant-derived nanoparticles (NPs), which can be easily produced in high levels at relatively lower costs. Like EVs, these nanoparticle-based systems also contain bioactive molecules, including polyphenols (which are known antioxidants) and microRNA, and they can deliver drugs to target organs in our bodies.

Leveraging this knowledge, researchers from the Tokyo University of Science (TUS) recently developed bionanoparticles with anticancer activity, using corn (maize) as the raw material. Prof. Makiya Nishikawa of Tokyo University of Science, Japan, who led the research team in this endeavor, elucidates, "By controlling the physicochemical properties of nanoparticles, we can control their pharmacokinetics in the body; so, we wanted to explore the nanoparticulation of edible plants. Maize, or corn, is produced in large quantities worldwide in its native form as well as in its genetically modified forms. That is why we selected it for our study." The results of this study were published online on 24 November 2021 in Scientific Reports.

The team created a homogeneous mixture of super sweet corn in water, then centrifuged this corn juice at a high speed, subsequently filtering it through a syringe filter with a pore size of 0.45 μm. The filtered samples were then ultracentrifuged to obtain NPs derived from corn. The corn-derived NPs (cNPs) were approximately 80 nm in diameter. Quite interestingly, these cNPs also carried a tiny net negative charge of -17 mV.

The research team then set up experiments to see whether these cNPs were being taken up by various types of cells. In a series of promising results, the cNPs were taken up by multiple types of cells, including the clinically relevant colon26 tumor cells (cancer cells derived from mice), RAW264.7 macrophage-like cells, and normal NIH3T3 cells. RAW264.7 cells are commonly used as in vitro screens for immunomodulators―drugs that primarily target various cancer pathways.

The results were astounding: of the three types of cells, cNPs only significantly inhibited the growth of colon26 cells, indicating their selectivity for carcinogenic cell lines. Moreover, cNPs were able to successfully induce the release of tumor necrosis factor-α (TNF-α) from RAW264.7 cells. It is a well-documented fact that TNFα is primarily secreted by macrophages, natural killer cells, and lymphocytes―three key ingredients of our highly evolved immune system and which help mount an anticancer response. "The strong TNFα response was encouraging and indicated the role of cNPs in treating various types of cancer," explains Dr. Daisuke Sasaki, first author of the study and an instructor and researcher at TUS.

The research team then conducted a reporter assay with the enzyme "luciferase" (derived from fireflies), which is a sensitive reporter for studying various biological responses. This luciferase-based assay revealed that the potent combination of cNPs and RAW264.7 cells significantly suppressed the proliferation of colon26 cells. Finally, the research team studied the effect of cNPs on laboratory mice bearing subcutaneous tumors. Once again, the results were astonishing: injecting cNPs into colon26 tumors on a daily basis significantly suppressed tumor growth, without causing serious side effects, or weight loss.

"By optimizing nanoparticle properties and by combining them with anticancer drugs, we hope to devise safe and efficacious drugs for various cancers," observes an optimistic Prof. Nishikawa.

Summarizing these impactful findings, Dr. Kosuke Kusamori, co-author and assistant professor at TUS says, "These cNPs exhibit excellent anti-tumor properties, are easy to develop, and are economically viable. Moreover, they do not exhibit any serious adverse effects, at least in mice so far!"

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Story Source:

Materials provided by Tokyo University of Science. Note: Content may be edited for style and length.

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Journal Reference:

1. Daisuke Sasaki, Kosuke Kusamori, Yukiya Takayama, Shoko Itakura, Hiroaki Todo, Makiya Nishikawa. Development of nanoparticles derived from corn as mass producible bionanoparticles with anticancer activity. Scientific Reports, 2021; 11 (1) DOI: 10.1038/s41598-021-02241-y

https://www.sciencedaily.com/releases/2022/02/220214111804.htm

Transient BP spikes coupled to learning in brain

 Minor everyday rises in blood pressure due to short-term stressors can be linked to a brain area that controls conscious and learned motor skills. This discovery, presented by University of Gothenburg researchers, paves the way for a chance to influence the rises in blood pressure and, in the long run, prevent hypertension.

In roughly half of all people with hypertension -- persistently high blood pressure (BP) -- there is no known cause. One plausible theory is, however, that hypertension might be the result of a long period of many recurrent BP peaks. Hundreds or thousands of micro-stress events may occur daily -- the telephone ringing, a car horn sounding in the street -- with BP spiking every time as a result.

For nearly 20 years now, a University of Gothenburg research group has been investigating how this kind of micro-stress affects nerve signals to our muscles and the throughput (perfusion) of blood in their vessels (muscle vasculature). In half of the over 150 men included in the group's studies to date, the pattern of their reaction system leads to BP peaks, while for the other half the reactions taking place in their bodies do not bring about any change in BP.

Ultramodern brain-imaging techniques

The latest results are published in Scientific Reports. For the study, 20 men aged 19-45 were examined. The experiment involved triggering a response in the nervous system with unexpected electric shocks that emulate the sudden and/or stressful stimuli to which we are exposed daily. The researchers combined two measurement methods. In one, a traditional research technique called microneurography, very thin needle electrodes are used to probe the signaling in nerve fibers (specifically, muscle sympathetic nerve activity, MSNA) directed to the vascular bed (blood vessels) of the muscles. The other was a modern brain-imaging technique known as magnetoencephalography (MEG).

For the first time, the researchers can now link the increased susceptibility to micro-stress to a reflex-like signal in the brain. The brain area (the "rolandic area") that activates the signal controls several conscious brain functions. This finding opens the question of whether the BP peaks may be learned and could therefore also, with training, be eliminated.

"We see a surprisingly strong connection between the peripheral autonomic vascular reaction, which takes place subconsciously, and a reaction pattern -- one that was already previously well known -- in a part of the brain where emotional impressions and motor skills undergo conscious interpretation. This raises questions about how independently the 'autonomic nervous system', as it's called, really works," says Mikael Elam, Professor of Clinical Neurophysiology at Sahlgrenska Academy, University of Gothenburg.

Long road ahead to clinical use

The idea that the discovery might come to be used to prevent hypertension is not unrealistic, but much research remains to be done.

"If we can develop ways of boosting the signal-to-noise ratio, in the future it may be possible to extract the relevant brain signals from a regular electroencephalogram [EEG], which is available in every Swedish hospital today. That would enable us, at an early stage, to identify people who react with BP spikes before they develop hypertension. Many other opportunities for preventive measures and research would then follow," says Justin Schneiderman, Senior Lecturer in experimental multimodal neuroimaging at Sahlgrenska Academy, University of Gothenburg.

Environmental factors decisive

Interestingly, our environment seems to matter more than our genetic code when it comes to which reaction pattern we develop, and thus whether we experience many daily BP spikes or not. An earlier study by the research group on identical twins showed that basic activity in the twins' blood-vessel-regulating autonomic nervous systems was very similar, while their stress-triggered reactions diverged.

"One may speculate that, today, many people have learned to suppress the primitive fight-or-flight response, since it's not that relevant in modern society. It's an impulse that prepares us for action, by reducing the vasoconstrictor nerve activity and thereby increase blood flow in the muscles. In terms of long-term health consequences, it might be beneficial to preserve the old flight-or-fight impulse in response to sudden stressors," Elam ponders.

A wide-ranging collaboration

The research group hopes to be able to facilitate studies at the population level, monitoring large groups of people over a long period. This would enable investigation of, first, whether individuals with reaction patterns that cause many peaks in blood pressure during the day are indeed at increased risk of developing hypertension later in life and, second, whether influencing this reaction pattern is feasible.

The research that maps the biological processes and signals controlling autonomic regulation of our blood vessels is taking place in a wide-ranging collaboration involving the University of Gothenburg, Sahlgrenska University Hospital, and Chalmers University of Technology.

FACTS ABOUT HYPERTENSION

• Hypertension (chronically high BP) is the main treatable cause of illness and death worldwide.
• The risk of developing hypertension is affected by many different factors, including obesity, smoking, type 2 diabetes, and kidney disease. In about half of cases, however, an underlying explanation is lacking.
• It may take up to some 15 years to develop hypertension, a condition defined as sustained systolic BP of 140 mmHg (millimeters of mercury, a unit for measuring blood pressure) or higher, or diastolic pressure of 90 mmHg or higher.
• Hypertension elevates the risk of several dangerous illnesses, such as heart attack and stroke, and of premature death.

Story Source:

Materials provided by University of Gothenburg. Note: Content may be edited for style and length.

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Journal Reference:

1. Bushra Riaz, John J. Eskelin, Linda C. Lundblad, B. Gunnar Wallin, Tomas Karlsson, Göran Starck, Daniel Lundqvist, Robert Oostenveld, Justin F. Schneiderman, Mikael Elam. Brain structural and functional correlates to defense-related inhibition of muscle sympathetic nerve activity in man. Scientific Reports, 2022; 12 (1) DOI: 10.1038/s41598-022-05910-8

https://www.sciencedaily.com/releases/2022/02/220214111815.htm

Behind a good mutation: How a gene variant protects against Alzheimer’s

 While the word "mutation" may conjure up alarming notions, a mutation in brain immune cells serves a positive role in protecting people against Alzheimer's disease. Now University of California, Irvine biologists have discovered the mechanisms behind this crucial process. Their paper appears in the journal Alzheimer's and Dementia.

The investigation centered on a variant of the PLCG2 gene, which makes the instructions for producing an enzyme important to brain immune cells called microglia. "Recently the mutation, which is known as P522R, was shown to lower the risk of developing late-onset Alzheimer's," said Hayk Davtyan, Ph.D., senior researcher in the laboratory of Mathew Blurton-Jones, professor of neurobiology & behavior, where the study was conducted. The project was led by assistant project scientist Christel Claes, Ph.D., the paper's first author.

The scientists used CRISPR gene-editing technology to generate the protective mutation in human stem cells and then implanted microglia derived from those stem cells into humanized rodent models of Alzheimer's disease.

"Our research showed for the first time that the P522R variant increased expression levels of several microglial genes that are reduced in people with Alzheimer's. This provides some of the first evidence to explain how this protective mutation might reduce Alzheimer's risk," Davtyan said.

The variant also increased the number of T-cells, or white blood immune system cells, in the brain suggesting that it may increase the activation of other important aspects of immune function.

The results will help in designing further studies to understand exactly how microglia and T-cells interact to slow Alzheimer's progression.

"Beyond that, the next step could be to identify drugs that can safely increase the activity of the PLCG2 enzyme and further promote protective microglial functions," he said.

First author Christel Claes wonders whether a TREM2 stimulating antibody, like the one currently in a Phase 2 clinical study from Alector (AL002), could exert similar protection in AD patients as the P522R variant.

"It is well known that the PLCG2 P522R mutation increases TREM2 downstream signaling, an AD risk variant, thus it will be very interesting to study the effect of TREM2 stimulating antibodies on microglia-T cell crosstalk. Studies like ours pave the way to find new strategies to treat or prevent this disease that is taking such a toll on humanity, this is what drives us as neuroscientists." said Davtyan.

The project was supported by a BrightFocus Postdoctoral Fellowship, the Cure Alzheimer's Fund, National Institutes of Health and National Institute on Aging.

Story Source:

Materials provided by University of California - Irvine. Note: Content may be edited for style and length.

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Journal Reference:

1. Christel Claes, Whitney E. England, Emma P. Danhash, Sepideh Kiani Shabestari, Amit Jairaman, Jean Paul Chadarevian, Jonathan Hasselmann, Andy P. Tsai, Morgan A. Coburn, Jessica Sanchez, Tau En Lim, Jorge L. S. Hidalgo, Christina Tu, Michael D. Cahalan, Bruce T. Lamb, Gary E. Landreth, Robert C. Spitale, Mathew Blurton‐Jones, Hayk Davtyan. The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model. Alzheimer's & Dementia, 2022; DOI: 10.1002/alz.12577

https://www.sciencedaily.com/releases/2022/02/220214144039.htm

Biophysical model helps better diagnose and treat osteoarthritis

 Scientists from Rochester Institute of Technology and Cornell University have teamed up to explore cartilage tissue's unique properties with the hopes of improving osteoarthritis diagnosis and treatment. The team published a new paper in Science Advances outlining their findings.

Cartilage tissue in our knee and elbow joints is just a few millimeters thick but can bear loads up to 10 times the body's weight and withstand a few hundred thousand loading cycles with minimal damage over a person's lifespan. But the tissue does not regenerate once people reach adulthood, and damage to cartilage can be a precursor to diseases like osteoarthritis. RIT's biophysics modelers and Cornell's experimentalists examined what mechanically happens to cartilage tissue at the microscopic level in response to shear to help drive advances in medical imaging.

"The goal was to find a mechanistic biophysics framework that can make realistic predictions about what kind of changes are taking place in cartilage mechanics and function during various disease pathways," said Moumita Das, co-senior author of the paper and an associate professor in RIT's School of Physics and Astronomy. "This mathematical model is informed by experimental data, so we can combine it with noninvasive measurements like MRIs. With a map of properties for healthy and damaged cartilage tissue, doctors can make predictions about when surgical intervention is necessary just from imaging without having to do invasive procedures."

RIT Postdoctoral Research Associate Jonathan Michel served as co-lead author on the paper, and Pancy Lwin, a mathematical modeling Ph.D. student from Myanmar, also served as a co-author. Cornell's contributions were directed by Professor Professor Itai Cohen and Professor Lawrence Bonassar.

The paper builds on another recent study the RIT-Cornell team published in Soft Matter that looks at how cartilage's properties resist fracture and how we can tune artificial materials to mimic those properties.

"As far as humanmade synthetic materials, nothing anyone has come up with to date can compare to cartilage," said Das. "If we can understand the origins of cartilage's robust and resilient properties, it can help us engineer tissues to replace cartilage or make other materials for applications such as soft robotics."

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Story Source:

Materials provided by Rochester Institute of Technology. Original written by Luke Auburn. Note: Content may be edited for style and length.

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Journal Reference:

1. Thomas Wyse Jackson, Jonathan Michel, Pancy Lwin, Lisa A. Fortier, Moumita Das, Lawrence J. Bonassar, Itai Cohen. Structural origins of cartilage shear mechanics. Science Advances, 2022; 8 (6) DOI: 10.1126/sciadv.abk2805

https://www.sciencedaily.com/releases/2022/02/220214154902.htm

COVID: Why are rapid tests banned in China?

 As the omicron variant continues to spread around the world, the demand for rapid antigen tests (RAT) for COVID-19 has also increased. Last month, the White House announced that Americans will be able to start ordering free RATs on January 19, as Washington purchased 1 billion RATs in January.

While Western countries have been relying on RATs as an alternative to their often overloaded PCR-testing system, China remains one of the few countries that almost exclusively relies on PCR tests to identify cases.

PCR tests search for viral genetic material like nucleic acids or RNA while RATs seek pieces of proteins infected by the virus. PCR tests are normally more precise than RATs because they are more sensitive. This means that antigen tests need a higher concentration of the virus than PCR tests to show positive results.

According to data from China's National Medical Products Administration at the end of 2021, China approved 68 new COVID-19 test reagents, including 34 nucleic acid testing reagents, 31 antibody testing reagents, and only three antigen testing reagents.

Chinese-made RATs globally widespread

Even though many RATs manufactured in China haven't been approved domestically, Chinese media reports show that at least 10 kinds of RATs manufactured in China have been approved in countries like the US, UK, Germany, Canada, and Greece.

Some experts think that the reason why China hasn't begun to roll out RATs on a mass scale is because of the country's persistence in enforcing the zero-COVID strategy. "China's upholding of the zero-COVID policy in the foreseeable future determines that rapid antigen tests may not be quite as effective in the current stage," said Xi Chen, an associate professor of health policy and economics at the Yale School of Public Health.

Other experts agree with Chen's assessment. According to Mei-Shang Ho, a research fellow at the Institute of Biomedical Sciences at Academia Sinica in Taiwan, because RATs are not so sensitive to a low viral load, PCR testing is the preferred method for countries upholding the strategy of identifying all existing cases in the community.

"For China, they need to identify all infected people, including the asymptomatic individuals, so it's more accurate for them to reach that goal by relying on PCR tests," she told DW.

The emergence of the omicron varianthas also posed new challenges to the accuracy of RATs. According to Chunhuei Chi, director of the Center for Global Health at Oregon State University in the United States, some recent studies suggest that because the omicron variant may be concentrated more around patients' throats or mouths in the beginning, when they try to take samples from their noses using RATs, the sensitivity of the tests may be lower.

"The real reason for this has yet to be determined, but we now know that the antigen test is less accurate in the face of omicron variants," he told DW.

Will China ever start using RATs?

Experts seem to agree on the fact that as long as China upholds its zero-COVID strategy, it will be unlikely that Beijing begins using RATs on a widespread scale. "Since antigen tests are not so sensitive to low virus loads, the false-negative cases may threaten the zero-Covid strategy," Chen from Yale's School of Public Health told DW.

Chi from Oregon State University also points out that, unlike China, countries that have been using large amounts of RATs have shifted the goal of their pandemic-control measures to preventing serious symptoms and deaths.

"If the goal is to prevent serious symptoms and death, as well as to prevent hospitals from being overloaded, then these countries don't need to care too much about how accurate the tests are," he explained. "What they care about is preventing the number of infections from getting out of control.”

Additionally, other non-medical factors may also contribute to China's decision to not use RATs on a large scale, said Chi. "Since RATs are mostly carried out by citizens at home, authorities in China may have less trust in the results of those tests," he told DW.

In an interview with China's state-run China News Weekly, Bo-lin Tang, the sales director of Ningbo Dasky Life Science, said that one of the reasons why RATs are developing slowly in China is because there is almost no market for rapid tests. "Since PCR tests are viewed as the gold standard in China and the country's testing capacity can keep up with it, there is no room for rapid antigen tests,” he said.

Additionally, since China's National Medical Products Administration (NMPA) uses a lengthy process to review COVID-19 test kits, Tang said manufacturers may find it troublesome to go through the official process and get the certificate issued by China's NMPA.

Combining the strength of RAT and PCR tests

One solution that combines the benefits of both the RAT and PCR tests may be on the horizon for Chinese citizens. In a peer-reviewed study published in the journal Nature Biomedical Engineering on Monday, Chinese scientists from Shanghai's Fudan University said they have developed a COVID-19 test that can process results as accurately as PCR tests in less than four minutes.

The researchers collected nasal samples from 33 PCR-positive COVID-19 patients, 23 PCR-negative patients, six influenza-positive patients, and 25 healthy volunteers. The test accurately processed all cases without error in under four minutes, according to the study. But since the study was conducted on a small sample, Johns Hopkins University's expert Andrew Ching told DW that it will only make a difference if the 100% accuracy rate can hold up in a larger test sample.

For the time being, Chunhuei Chi thinks that RATs may not gain the trust of the Chinese authorities anytime soon.

"Assuming that China will slowly consider moving away from the zero-COVID strategy after the major political event this fall, RATs may start to be taken more seriously by Chinese authorities by then," he said.

Chen from Yale also thinks that China's manufacturing capacity for RATs may play a more important role in its future pandemic-control measures. "The large manufacturing capacity for antigen tests will become more important as the zero-COVID strategy eventually shifts," he said.

https://www.dw.com/en/covid-why-are-rapid-tests-banned-in-china/a-60772821

Gottlieb: Shots for kids under 5 delayed due to low Covid cases in trial

 The Food and Drug Administration’s plan to fast-track Pfizer’s Covid vaccine for children under 5 years old was delayed because of a “low number of cases overall in the clinical trial,” Dr. Scott Gottlieb told CNBC on Monday.

“Most kids are not getting symptomatic Covid,” said the current Pfizer board member and former head of the FDA. “One case in one direction or another can tip the perception of the vaccine’s overall effectiveness.”

“The FDA wanted to take the time for this data set to effectively settle down,” Gottlieb said on “Squawk Box.” “That point’s probably going to be after they’ve administered the third dose and have the data from that third dose.” He added, “At that point you’ll be able to get more of a fixed perception of the vaccine’s overall effectiveness” in that younger group, the only cohort not cleared in the U.S. for the shots.

The FDA had originally planned to consider authorizing two doses of what would ultimately be a three-dose vaccine for kids under 5 as soon as this month. However, the agency said Friday it’s now going to wait on data about the effectiveness and safety of a third dose, which Pfizer and its vaccine partner, BioNTech, have said won’t come until April.

“I suspect there’s only going to be 15% to 20% of parents who go out and get their young kids vaccinated,” should shots for children under 5 get emergency authorization, Gottlieb said. He added, “For the parents who were going to vaccinate their kids, this was very important.”

While children are overall at a lower risk of Covid, very young kids, especially those with preexisting health conditions, are still not in the clear, Gottlieb said. About 1,100 pediatric deaths have occurred from Covid since the beginning of the pandemic, with about 400 in kids under 5, the former FDA chief pointed out. By comparison, Gottlieb said, only five children have died from the flu in the last two years.

Gottlieb said he expects the Centers for Disease Control and Prevention to institute a “permissive recommendation,” rather than a mandate for children under 5 to get vaccinated. “They’re not going to say, ‘Children under the age of 5 should get vaccinated.’ They’ll say something like, ‘They could get vaccinated to reduce their risk,’” he said.

https://www.cnbc.com/2022/02/14/pfizer-director-dr-scott-gottlieb-shots-for-kids-under-5-delayed-due-to-low-covid-cases-in-trial.html