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Low-cost cancer treatment with a device the size of a microwave

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Low-cost cancer treatment with a device the size of a microwave

Low-cost cancer treatment with a device the size of a microwave. A Belgian biotech company is testing a device that produces cancer drugs in hospitals, reducing waiting times and the cost of treatment.

Low-cost cancer treatment with a device the size of a microwave

In this article we’re going to read about Low-cost cancer treatment with a device the size of a microwave. When cancer treatment with a chimeric antigen receptor T cell, or CAR-T, works, it can seem miraculous. About half of leukemia and lymphoma patients, and about a third of myeloma patients, get a complete cure with a single injection of immune T cells that have been genetically modified to find and kill cancer in the blood. CAR-T treatment for acute lymphoblastic leukemia, which is the most common type of childhood cancer, has shown a cure rate of up to 90%. The first two patients treated with CAR-T in 2010 were adult men suffering from end-stage acute lymphoblastic leukemia. They were still in remission a decade after treatment.

Since 2017, the US Food and Drug Administration (FDA) has approved a total of six CAR-T therapies, all for blood cancers. Many studies have been conducted with the aim of using CAR-T therapy on solid tumors, but none are yet at the clinical trial stage. Two of these treatments, known as “Yescarta” and “Tecartus”, have earned 1.5 billion dollars for Kite Pharma in 2022 alone. Until recently, CAR-T therapies were mainly considered a last resort for patients who have tried other drugs, but CAR-T therapy can be used earlier in the treatment process and is likely to have a big impact. Last year, Yescarta was approved as a second-line treatment for large B-cell lymphoma. Despite this, drug makers are currently facing a problem.

A survey conducted in 2022 by Mayo Clinic researchers found that the average time on the waiting list for CAR-T treatment was six months, and only a quarter of patients eventually received it. Another quarter was able to enter a clinical trial for treatments that have yet to be approved. In the past few years, Bristol Myers Squibb, Kite Pharma, and Novartis have all experienced manufacturing problems with their CAR-T therapies. Johnson & Johnson (J&J) and Legend Biotech (Legend Biotech) decided in March to stop launching their CAR-T therapy, Carvycti, in the UK due to production constraints.

Unlike conventional drugs, autologous CAR-T injections are living drugs that are customized for each patient. Blood sampling of patients is usually done in a hospital or special center. Once isolated, the T cells are shipped frozen to a biomanufacturing facility where they are genetically reprogrammed to express a tumor-seeking molecule called a chimeric antigen receptor (CAR) on their surface. The modified cells are placed in an incubator for days or weeks until their numbers increase enough to create a therapeutic dose. After several stages of quality testing, the modified CAR-T cells are frozen and returned to the hospital to be injected into the patient. This process usually takes a minimum of two weeks and a maximum of eight weeks.

Current CAR-T treatments cost between $300,000 and $400,000. Travis Young, vice president of the biology department at the non-profit California Biomedical Research Institute (Calibr), said: “The reason for the high cost of treatment is that the production process must be highly controlled at every point of it.” This requires a trained technician, clean rooms, and infrastructure for transportation and freezing. The most important time is pre-release testing to ensure product sterility and potency. There are many possibilities for problems. The supply chain is still in its infancy, and it’s not just about the infrastructure, it’s about the number of people who need to be trained to do the job.

Companies are tackling these challenges in a variety of ways, aiming to reduce the complexity, time, and cost of delivering CAR-T therapies to more patients. One of the more unlikely competitors is Belgium-based Galapagos NV, which last June announced a bold plan to produce these expensive treatments faster and more cost-effectively. The program proposes developing treatments not in a centralized location, but at the point of care, using a small automated device the size of a home microwave.

Galapagos had no prior experience with CAR-T therapy and had only marketed one product in Europe, the UK, and Japan since its inception in 1999. This product was the drug “Jyseleca” for the treatment of ulcerative colitis and rheumatoid arthritis, whose sales in 2022 were reported to be equal to 95 million dollars. The drug has recently undergone a series of clinical trials, but it has one special advantage: Paul Stoffels, the new CEO of Galapagos and former chief scientific officer of Johnson & Johnson.

When Stoffels left J&J at the end of 2021, he had one of the most enviable track records in the pharmaceutical industry. This Belgian-born doctor and specialist in infectious diseases during his training was in charge of the groups that produced 25 new drugs; including two successful cancer drugs, breakthrough treatments for HIV and tuberculosis, and vaccines for Ebola and Covid-19. Although Carvycti was approved a few months after Stoffels left, it was developed under his watch. During Stoffels’ tenure, J&J’s pharmaceutical sales more than doubled from $22.5 billion in 2009 to $45.6 billion in 2020. Seven of the drugs developed under Stoffels’ supervision have been added to the “World Health Organization’s” (WHO) list of essential drugs, which means that they are considered necessary to maintain health.

Stoffels’ stint in the Galapagos gives him the opportunity to demonstrate his ability in a larger company. Immediately after taking over as CEO last April, Stoffels orchestrated a major pivot, buying two startups working on different aspects of CAR-T therapies and manufacturing them, and four months later hired 200 people working on drug programs. They were working older, fired.

Galapagos sets up manufacturing units at each of its partner hospitals, which includes training people, installing equipment, and validating the manufacturing process, Stoffels explained about the process. This is a new approach but much simpler than centralized manufacturing. In centralized manufacturing, you have to invest several hundred million dollars in a building, hire between 500 and 1,000 people, train them, and produce the drug there, but for us, the heavy lifting of this technology has already been done.

From a biological perspective, using diseased cells that have never been frozen has advantages that affect cell health. Newly generated CAR-T cells, after re-injection into the patient, show robust and consistent growth, which helps minimize a common side effect of CAR-T therapy called cytokine release syndrome, Stoffels continued. This syndrome is an aggressive reaction to immunotherapy that causes fever, nausea, and fatigue. The fact that the treatment can be done in seven days allows people with a very short life expectancy to receive this type of treatment. The first patient treated with CAR-T, who came to the hospital with acute respiratory distress syndrome and severe tumor recurrence, is still in excellent condition. This could never have been done with CAR-T the old way and in one centralized location.

Read More: Scientists discovered the secret of DNA’s X shape

Decentralization, simplification, and automation of the entire process will significantly reduce CAR-T costs, Stoffels added. The time required and the amount of work that needs to be done make CAR-T treatments expensive. If you put four or five systems in a hospital room, you can treat 200 patients a year using only a small staff.

Galapagos will not be immune to shortages of chemical reagents and other raw materials that affect other companies. “All the challenges are compounded by not having trained technicians to do the work,” Travis Young said. Technicians don’t need a lot of training because the systems require a lot less manipulation, but whenever you distribute these systems across hospital centers, you lose some control over them all.

After all, Stoffels has made the impossible possible before, and he’s done it many times, and he doesn’t seem to be giving up. He added: “I have worked all my life trying to get access to medicines.” This work is also such a mission. New science allows us to do new, difficult, and different things, and if you don’t start, you will never reach the goal.

 

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The study that first showed the benefits of ADHD

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ADHD

In a new study, it has been hypothesized that some genetic traits associated with attention deficit hyperactivity disorder (ADHD) can actually be beneficial by increasing exploratory behaviors.

The study that first showed the benefits of ADHD

While current diagnostic definitions of attention-deficit/hyperactivity disorder (ADHD) are relatively new, the condition has been recognized and defined by clinicians under various names for centuries.

According to NA, recent genetic studies have shown that this disease is highly hereditary, which means that most people with this disease genetically inherited it from their parents.

Depending on the diagnostic criteria, between 2% and 16% of children can be classified as having ADHD. In fact, the increase in diagnosis rates in recent years has led some doctors to argue that the disease is overdiagnosed.

What is relatively clear, however, is that the behavioral traits that underlie ADHD have potentially been genetically present in human populations for a long time, leading some researchers to speculate on the evolutionary advantages of this What could be the conditions?

Imagine you are part of a wandering tribe of early humans. Your group comes across a field full of one type of fruit and everyone is faced with one big question. Do you settle on a farm and exploit its fruit supply until it’s all gone, or do you quickly pick up what you can and continue exploring for more diverse foods?

This opposition to exploitation or exploration is fundamental to the survival of all animals. At what point does the risk of staying in one place outweigh the risk of moving to find what’s next?

In the early 2000s, a team of scientists studied the genetics of a unique tribe of people in northern Kenya. This tribe, known as Ariaal, has traditionally been incredibly nomadic and nomadic since ancient times, and they have continued to live in this way. Some members of the Arial tribe settled down during the 20th century and adopted modern farming methods, while others continued to live as nomadic herders.

Read More: Flu-killer cells have been discovered in the lungs

Scientists compared the genetic and health differences between these two groups of the Arial tribe and discovered something incredibly interesting. In general, all people of the Arial tribe carry a unique genetic mutation called DRD4/7R. This genetic trait has previously been commonly identified in people with ADHD.

This genetic mutation in today’s children who have been diagnosed with ADHD is generally associated with restlessness and distraction, and in those children of the Ariel tribe who were used to the behaviors of staying still settling down, and avoiding moving, this gene was associated with health. Poor and disruptive behaviors in class were related. But in Aryalees who still lived a traditional nomadic life, this gene mutation was associated with better nutritional health and strength.

The DRD4/7R mutation is associated with increased food and drug cravings, novelty seeking, and ADHD symptoms, explained Dan Eisenberg, lead author of the 2008 study. It is possible that in a nomadic environment, a boy with this gene mutation would be able to more effectively defend livestock against invaders or find water and food sources, but these same tendencies may be limited to fixed jobs such as setting up a school, farming, or selling goods. not useful

So an interesting hypothesis emerged. Whether the genetic traits of ADHD can be somewhat beneficial to a tribe, as it predisposes some individuals to “exploration” What appears in modern times as unrest and restlessness could actually have been beneficial to tribes that were looking for food.

David Barak from the University of Pennsylvania along with a team of colleagues tested this hypothesis experimentally. They produced a unique game where players were given eight minutes to collect as many berries as possible by hovering over a bush. Each time they picked berries from a bush, the player’s harvest was reduced slightly, but if they went to a new bush, there was a time penalty.

So what did most players do? Did they stick to the original bush? Or risk wasting time trying another plant to see if it bears more fruit? The same basic question, exploration or exploitation?

About 450 people participated in this experiment and all were simultaneously screened for ADHD symptoms. Not surprisingly, the researchers found that people with higher ADHD scores reached out to new plants sooner than others, but more importantly, people with ADHD tended to collect a larger volume of berries overall.

In a recently published study, Barak and his colleagues noted that participants without ADHD traits tended to overeat individual plants.

Finally, looking at the optimal withdrawal strategy for this game, it was found that players with high ADHD scores were more successful overall.

“We found that participants who screened positive for ADHD gave up the bushes more easily and achieved higher rates of reward than participants who screened negative,” the researchers wrote in their conclusion. Given that participants stayed more on a plant in general, those with high ADHD scores made more exploratory decisions, consistent with the predictions of optimal search theory, and thus behaved more optimally.
It should be noted that these findings do not represent a definitive verdict on the possible evolutionary benefits of ADHD, but they provide compelling and plausible reasons why a small percentage of humans still have these traits.

In the 21st century, we may have pathologized ADHD as a negative disorder, but this could simply be because these characteristics no longer fit the world we have constructed. So in a different context, a person with ADHD may be the savior of a society with their restless exploration of new fields.

This new study is published in the journal Proceedings of the Royal Society B.​

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Flu-killer cells have been discovered in the lungs

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A hidden army of flu-killer cells has been discovered in the lung

A hidden army of flu-killer cells has been discovered in the lungs. A group of “University of California Riverside” researchers in their new research have discovered a group of virus-eating cells in the lung that can fight influenza.

A hidden army of flu-killer cells has been discovered in the lungs

Scientists have long thought of the fluid-filled sac around our lungs as merely a barrier to external damage, but new research shows that this sac also contains powerful virus-eating cells that enter when an influenza infection occurs.

According to ScienceMag, these cells should not be confused with phages that infect bacteria. These cells, called macrophages, are immune cells produced in the body.

“Juliet Morrison” (Juliet Morrison), a virologist at, “The University of California Riverside” (UC Riverside) and head of this research said: Macrophages swallow bacteria, viruses, cancer cells, and dying cells. They grab and destroy anything that looks alien. We were surprised to find them in the lungs because no one had seen anything like that before.

In this research, it is explained how macrophages leave the external cavity and enter the lungs during influenza. They reduce inflammation there and lower the level of disease. “This research shows that it’s not just what happens in the lung that matters, but what happens outside the lung as well,” Morrison said. Cells not normally associated with the lung can have important effects on lung disease and health.

He added: Since this structure contains liquid, it prevents the lungs from collapsing. Despite this, researchers haven’t thought much about the fact that it might contain an entire organ. Our research may change this perception.

Researchers initially sought to answer a more general question. The question was which type of cells are present in the lung when you get influenza? They obtained existing data on lung-related genes from research on mice that either died or survived the flu. Then, they mined the data using an algorithm to predict the types of cells that change in the lungs during influenza. “We analyzed the data to determine which immune cells were present in the lung tissues,” Morrison said. That’s when I realized that maybe we have an unknown external source of cells in the lung.

Read More: This robot can open the veins with high precision

Then, using a laser-based method, the researchers tracked the macrophages entering the mice’s lungs and found out what would happen if they took these cells out. “When you take them out of the mouse lung, you see disease progression and increased lung inflammation,” Morrison continued.

A hidden army of flu-killer cells has been discovered in the lung
Morrison hopes the research will encourage other scientists to re-evaluate data sets from older studies. He added: Our method was to make a new use of the available information and finally we were able to see something new.

In their future research, the research group hopes to understand which protein tells the macrophages to move into the lungs. Once the protein signals are identified, it may be possible to discover drugs that increase macrophage numbers or activity.

A strategy to strengthen the human defense system against infection rather than developing another antiviral drug could provide a treatment for influenza that is effective for a longer period of time. Morrison is interested in host therapy because antibiotic and antiviral drug resistance is a growing problem.

This problem occurs when microbes, such as bacteria and fungi, gain the ability to defeat drugs designed to kill them. Improper use and overdose of drugs accelerate this problem. According to the report of the “American Center for Disease Control and Prevention” (CDC), more than 2.8 million drug-resistant infections occur in this country every year, and as a result, more than 35 thousand people die.

“If we can boost what’s killing the infection in us, we’re probably going to have a better outcome and be less likely to become resistant to the drug,” Morrison said. The immune system is very complex, but our best long-term job is to work with what we have instead of chasing treatment-evasive viruses.

This research was published in the journal “PNAS”.​

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Why do we get old?

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Aging is an inevitable fate for all living organisms and many scientists are trying to reverse this process by discovering effective factors. Now a new study shows that DNA damage may be the main cause of aging. So why do we get old?

Why do we get old?

Processes and pathways that run smoothly in our youth begin to fail as we age. Over time, these breaks build up and lead to symptoms like loss of muscle mass, weakened immune systems, memory problems, and more that we will all experience in the future.

According to Forbes, what we see on the skin is reflected at the genetic level, creating obvious differences between young and old adults, but the exact reasons for these age-related genetic changes have not been well understood. A new study suggests that DNA damage may be to blame for aging. So why do we get old?

The genetic fingerprint of aging

Genes make the world go round. It sounds like an exaggeration, but it’s true. Each of the processes we depend on for life is somehow shaped by genes. Remember that genes serve as blueprints for protein production. Without proteins, everything stops, and ultimately, they are molecules that perform functions.

Whether a protein is produced when, where, and how much it is produced is precisely regulated by a process called gene expression. Gene expression is essentially a genetic on/off switch. For example, when a person becomes ill due to a viral infection, their body begins to turn on genes related to the immune response, thereby mobilizing the appropriate immune cells to help defend against the threat. When gene expression is properly regulated, cell function proceeds smoothly, but if the balance is disturbed, genes that should be off may remain on, and vice versa. Also, too much or too little protein may be produced.

Aging is characterized by a specific pattern of gene expression. In a sense, it can be said that aging has a specific genetic fingerprint. Just like a thief leaves his fingerprints at a crime scene, age leaves its mark, and this is true of all animal species, from tube worms to humans.

Read More: Can the aging process be slowed down?

Changes in gene expression associated with aging have been known for some time, but answering what triggers these changes in the first place has been surprisingly difficult. We know what aging looks like at the genetic level, but we don’t know why it happens.

Why do we get old?

From DNA to RNA

Protein production is a complex, multi-step process, and as with any complex process that has multiple moving parts, there is room for error. In fact, the findings of this new research show that changes in gene expression with age may be related to defects in protein production. It seems that damage to DNA is associated with damage to an important step called “transcription”.

Proteins are made from RNA, but our genes are stored in the form of DNA. Therefore, DNA must first be converted into RNA. In technical language, this work is called transcription. Why is this genetic procedure needed? Our DNA is stored in the nucleus of cells and does not leave this area of the cell to minimize damage, but protein production takes place in the cytoplasm. Therefore, genetic information must reach the cytoplasm from the nucleus.

This is where mRNA, or to be more precise, “messenger RNA” (mRNA) comes into play. While DNA is used for long-term storage, messenger RNA serves as a single-use set of genetic instructions. A messenger RNA encodes a copy of a specific gene and transfers it from the nucleus to the cytoplasm; Where the gene can be converted into a protein. The process is similar to copying part of a rare book that you need but can’t get out of the library.

The body even has its own genetic photocopying machine called RNAi polymerase II, or RNAPII. Arane polymerase II is a complex of several proteins that, depending on the gene that needs to be transcribed, attaches to a specific segment of DNA and then moves along the target gene, delivering a copy of the complementary arane. The resulting RNA strand, called the transcript, is the precursor to the messenger RNA.

In this study, Akos Gyenis, Jiang Chang, and their colleagues at the Erasmus MC Medical Center in the Netherlands discovered that in older mice, RNAi polymerase II often fails when transcribing DNA into Arani starts to stop. Analyzing the livers of two-year-old mice, they found that up to 40% of all polymerase II arane complexes were stopped. Additionally, each stalled set likely blocks three others behind it, causing the DNA strands to line up until the blockage is resolved. The researchers found that larger genes were particularly susceptible to these issues, leading to a bias towards the expression of small genes.

When transcription stops, gene expression also stops. As a result, many cellular pathways begin to fail. They are deprived of the proteins they need to function properly. This includes all pathways that malfunction with age. In other words, the genetic fingerprint created by interrupted transcription is the same as that created by aging, suggesting that they are closely related. Pathways affected include those involved in nutrient sensing, cellular debris clearance, energy metabolism, immune system function, and the ability of cells to cope with injury. All of these things play a vital role in shaping longevity.
In the next step, the researchers sought to understand the cause of the arrest of Aran polymerase II in aged mice. Their suspicions led to DNA damage that was spontaneous and internal. Gene expression patterns in cells exposed to DNA-damaging agents are very similar to those seen during normal aging. Premature aging disorders such as Cockayne syndrome are also characterized by DNA damage. Normal DNA repair mechanisms malfunction and result in the stalling of polymerase II at sites of damage known as lesions. Considering these similarities, scientists speculated that DNA damage could also be involved in normal aging.

To test their hypothesis, the researchers looked at genetically modified mice that lacked the normal DNA repair system and were prone to DNA damage. These mice showed many features of premature aging; Including their life span which was significantly shortened. As expected, the transcription speed was significantly lower in these mice compared to the healthy group.

Although we have a good understanding of how gene expression changes with age, we do not fully understand what causes these genetic changes. This situation is just like looking at the symptoms of a disease without knowing the root cause. This new research suggests one possible mechanism is the DNA damage that accumulates in RNAi polymerase II as it attempts to transcribe the template strand into RNAi. When RNAi polymerase II hits a site of damage, it stalls and interferes with transcription, disrupting several important cellular pathways.

Although this research does not yet have any immediate therapeutic implications, research of this type helps us better understand the inner workings of the aging process. The deeper our understanding, the more likely it is to develop effective drug interventions. Until then, it’s best to avoid behaviors that pose a risk of DNA damage, such as smoking and exposure to UV rays. Temporary programmed caloric restriction may also help reduce transcriptional pressure.

This research was published in “Nature Genetics” magazine.

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