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Emily Whitehead was diagnosed with acute lymphoblastic leukemia (ALL) when she was just five years old. Acute lymphoblastic leukemia is a type of cancer of the blood and bone marrow that affects white blood cells, and is most common in children ages three to five. Whitehead needed chemotherapy, but after two years, it was unsuccessful. Her health was rapidly declining, and the local hospital told them to go home and enjoy the days they had left with her. But Whitehead’s parents refused to give up on their daughter and turned to the Children’s Hospital of Philadelphia (CHOP) for help.. There, they learned about a clinical trial that had just started involving CAR T-cell therapy, which genetically alters a patient’s white blood cells to fight cancer cells. Whitehead’s doctor, Dr. Grub, says this therapy is a game-changer for blood cancers and is a great option for those who relapsed and don’t have their cancer under control. In 2012, Whitehead became the first pediatric patient in the world to receive this type of therapy. Today, she is 17 years old and just celebrated being ten years cancer-free!

“I’m feeling great. I’m really healthy. I’m driving now, I got my driver’s license in January.”

Not all patients who receive CAR T for relapsed ALL reach the same outcome as Emily. Currently, more than 90% of patients who receive CAR T-cell therapy for relapsed ALL go into remission; approximately 50% of those patients will remain cancer free. Researchers are continuing to advance the field so that more patients never relapse. Because CHOP is the pediatric oncology program with the most CAR T experience — having to date treated more than 440 patients, who have come to CHOP from across the globe — the program remains poised to further improve those outcomes.

In addition, Dr. Grupp says there has been a change in thinking surrounding enrollment in clinical trials for cancer patients. Rather than waiting until a patient is nearly out of options to consider experimental treatment options, oncologists are recognizing patients who might qualify for CAR T-cell therapy and other clinical trials earlier in the process. While CAR T-cell therapy is good for blood cancers, doctors and researchers will be spending the next five to ten years trying to figure out how to make this work for other types of cancers such as breast cancer and lung cancer.

Source: https://www.chop.edu/

A new meta-analysis published today in the JAMA Network Open shows a strong association between the seasonal flu vaccine and a reduction in adverse cardiovascular outcomes within a year of follow up, particularly for high-risk patients. This is the strongest evidence to date that influenza vaccines are a key measure in the prevention of cardiovascular events, such as heart attacks.

“While we were already aware of this protective association, our previous systemic review and meta-analysis underscored the need for a large scale, adequately powered, and ideally global clinical trial to provide more robust and comprehensive data,” explained Bahar Behrouzi, MD and PhD candidate at the University of Toronto and lead author. “This study looked at randomized controlled trials from 2000-2021 that compared the influenza vaccine with either a placebo or control, in order to assess its impact on fatal and non-fatal cardiovascular events over the course of a year.”

The researchers found that 3.6 per cent of the 4,510 clinical trial participants who received a flu vaccine experienced a major cardiovascular event afterwards in the following year, compared with 5.4 per cent of the 4,491 patients who received a placebo or control, which is a significant difference.

“Given the pervasive nature of heart disease globally, it is critical that we leverage as many preventative clinical tools and treatments as possible to improve patient outcomes,” said Dr. Jay Udell, cardiologist at Women’s College Hospital and the Peter Munk Cardiac Centre at UHN, scientist at the Women’s College Research Institute, and senior author. “The effect sizes witnessed so far with the flu vaccine are comparable to other common preventative measures such as statins and beta blockers. Our work underscores the value of utilizing influenza vaccines as a mainstay in cardiovascular disease prevention.”

In light of the evidence, the authors advise clinicians to encourage their patients, particularly those with high cardiovascular risk, to get their annual flu shot, an intervention that remains underutilized despite being low cost, well tolerated, and impactful.

“Applying our findings more broadly, our study highlights the additional or secondary benefits often associated with vaccinations,” Udell stated. “In the current context of the COVID-19 pandemic and ongoing vaccine hesitancy, we are hopeful that our results highlight the positive ancillary benefits of vaccinations – providing greater motivation and encouragement for those who remain uncertain.”

Source: https://jamanetwork.com/
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https://www.womenscollegehospital.ca/

While immortality might forever be out of reach, a long, healthy retirement is the stuff dreams are made of. To that end, a recent study suggests that the kinds of memory problems common in old age can be reversed, and all it takes is some cerebrospinal fluid (CSF) harvested from the young. In mice, at least.

If this is sounding a little familiar, you might be thinking of a similar series of studies done back in the mid-2010s, which found that older mice could be generally ‘rejuvenated‘ with the blood of younger animals – both from humans and from mice. The FDA even had to warn people to stop doing it. This new study instead examined the links between memory and cerebrospinal fluid  (CSF), and the results show considerable promise, even providing a mechanism for how it works, and highlighting a potential growth factor that could mimic the results.

“We know that CSF composition changes with age, and, in fact, these changes are used routinely in the clinic to assess brain health and disease biomarkers,” Stanford University neurologist Tal Iram said. “However, we don’t know well how these changes affect the function of the cells in the aging brain.”

To investigate, the researchers, led by Iram, took older mice (between 18–22 months old) and gave them light shocks on the foot, at the same time as a tone and flashing light were activated. The mice were then split into groups, and either given young mouse CSF (from animals 10 weeks old) or artificial CSF. In experiments like this, if the mice ‘freeze’ when they see the tone and light, it means they’re remembering the foot shock, and are preparing for it to happen again. In this study, three weeks after the foot shocks were conducted (which the team called “memory acquisition“), the researchers tested the mice, finding that the animals that had been given the CSF from young mice showed higher-than-average freezing rates, suggesting they had better memory. This was followed up by a battery of other experiments to test the theory, which revealed that certain genes (that are different in young-versus-old CSF) could be used to get the same response. In other words, without needing to extract someone’s brain fluid.

“When we took a deeper look into gene changes that occurred in the hippocampus (a region associated with memory and aging-related cognitive decline), we found, to our surprise, a strong signature of genes that belong to oligodendrocytes,” Iram explained. “Oligodendrocytes are unique because their progenitors are still present in vast numbers in the aged brain, but they are very slow in responding to cues that promote their differentiation. We found that when they are re-exposed to young CSF, they proliferate and produce more myelin in the hippocampus.” Oligodendrocytes are particularly helpful because they produce myelin, a material that covers and insulates neuron fibers.

Fujifilm and the National Center of Neurology and Psychiatry (NCNP) have just released new research which shows that AI technology could help to predict whether or not someone is likely to get Alzheimer’s disease. By monitoring brain activity, Fujifilm and NCNP say that they are able to predict whether a patient with mild cognitive impairment (MCI) will progress to having dementia within two years with an accuracy of up to 88%.

Alzheimer’s disease is the most common cause of dementia and it is estimated that 55 million people worldwide have the neurological condition that causes loss of memory. As the population ages, it’s expected that by 2050, more than 139 million people will suffer from the life-changing condition Using advanced image recognition technology, Fujifilm and NCNP have developed a way in which they are able to monitor the progression of Alzheimer’s from three-dimensional MRI scans of the brain. Deep learning AI technology monitors the hippocampus and the anterior temporal lobe, two areas highly associated with the progression of Alzheimer’s and detects fine atrophy patterns associated with Alzheimer’s.

An MRI scan of the brain showing the progression of Alzheimer’s 

Atrophy is the progressive degeneration or shrinking of muscle or nerve tissues and in relation to dementia, it takes place in the brain. Two types of common atrophy’s are found in patients with MS – muscle atrophy which causes certain muscles to waste away and cerebral atrophy which is a loss of neurons and connections between neurons. The research shows that when AI technology learns an entire brain, it focuses not just on the two areas usually associated with Alzheimer’s but also on the cerebrospinal fluid (a clear colorless fluid found in your brain and spinal cord) and the occipital lobe which is the visual processing area of the brain. 

By learning to differentiate between areas of the brain that are less relevant to Alzheimer’s, it is much more likely that a highly accurate prediction can be made about the progression of mild cognitive impairment.

Source: https://www.digitalcameraworld.com/

Brigham and Women’s Hospital will test the safety and efficacy of a nasal vaccine aimed at preventing and slowing Alzheimer’s disease, the Boston hospital announced Tuesday. The start of the small, Phase I clinical trial comes after nearly 20 years of research led by Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the hospital. The trial will include 16 participants between the ages of 60 and 85, all with early symptomatic Alzheimer’s but otherwise generally healthy. They will receive two doses of the vaccine one week apart, the hospital said in a press release. The participants will enroll from the Ann Romney Center. A Phase I clinical trial is designed to establish the safety and dosage for a potential new medication. If it goes well, a much larger trial would be needed to test its effectiveness.

The vaccine uses a substance called Protollin, which stimulates the immune system.

“Protollin is designed to activate white blood cells found in the lymph nodes on the sides and back of the neck to migrate to the brain and trigger clearance of beta amyloid plaques — one of the hallmarks of AD [Alzheimer’s disease],” the hospital explains. It notes that Protollin has been found to be safe in other vaccines. “The launch of the first human trial of a nasal vaccine for Alzheimer’s is a remarkable milestone,” said Weiner in the hospital’s press release. “Over the last two decades, we’ve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimer’s, and it could also be given early to help prevent Alzheimer’s in people at risk.”

The researchers say they aim to “determine the safety and tolerability of the nasal vaccine” in the trial and observe how Protollin affects participants’ immune response, including how it affects their white blood cells. “The immune system plays a very important role in all neurologic diseases,” Weiner added. “And it’s exciting that after 20 years of preclinical work, we can finally take a key step forward toward clinical translation and conduct this landmark first human trial.”

“Research in this area has paved the way for us to pursue a whole new avenue for potentially treating not only AD, but also other neurodegenerative diseases,” said Tanuja Chitnis, MD, professor of neurology at Brigham and Women’s Hospital and principal investigator of the trial.

I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical are responsible for developing, manufacturing and commercializing Protollin.

Source: https://www.cbsnews.com/

During experiments in animal models, researchers at the University of Kansas (KU)  have discovered a possible new approach to immunization against Alzheimer’s disease (AD). Their method uses a recombinant methionine (Met)-rich protein derived from corn that was then oxidized in vitro to produce the antigen: methionine sulfoxide (MetO)-rich protein. This antigen, when injected to the body, goads the immune system into producing antibodies against the MetO component of beta-amyloid, a protein that is toxic to brain cells and seen as a hallmark of Alzheimer’s disease.

“As we age, we have more oxidative stress, and then beta-amyloid and other proteins accumulate and become oxidized and aggregated – these proteins are resistant to degradation or removal,” said lead researcher Jackob Moskovitz, associate professor of pharmacology & toxicology at the KU School of Pharmacy. “In a previous 2011 published study, I injected mouse models of Alzheimer’s disease with a similar methionine sulfoxide-rich protein and showed about 30% reduction of amyloid plaque burden in the hippocampus, the main region where damage from Alzheimer’s disease occurs.”

The MetO-rich protein used by Moskovitz for the vaccination of AD-model mice is able to prompt the immune system to produce antibodies against MetO-containing proteins, including MetO-harboring beta-amyloid. The introduction of the corn-based MetO-rich protein (antigen) fosters the body’s immune system to produce and deploy the antibodies against MetO to previously tolerated MetO-containing proteins (including MetO-beta-amyloid), and ultimately reduce the levels of toxic forms of beta-amyloid and other possible proteins in brain.

According to Moskovitz, there was a roughly 50% improvement in the memory of mice injected with the methionine sulfoxide (MetO)-rich protein versus the control.

The findings have been just published in the peer-reviewed open-access journal Antioxidants.

Source: https://today.ku.edu/

The relentless evolution of the COVID-causing coronavirus has taken a bit of the shine off the vaccines developed during the first year of the pandemic. Versions of the virus that now dominate circulation—Omicron and its subvariants—are more transmissible and adept at evading the body’s immune defenses than its original form. The current shots to the arm can still prevent serious illness, but their ability to ward off infection completely has been diminished. And part of the reason may be the location of the jabs, which some scientists now want to change.

To block infections entirely, scientists want to deliver inoculations to the site where the virus first makes contact: the nose. People could simply spray the vaccines up their nostrils at home, making the preparation much easier to administer. There are eight of these nasal vaccines in clinical development now and three in phase 3 clinical trials, where they are being tested in large groups of people. But making these vaccines has proven to be slow going because of the challenges of creating formulations for this unfamiliar route that are both safe and effective.

What could be most important about nasal vaccines is their ability to awaken a powerful bodily defender known as mucosal immunity, something largely untapped by the standard shots. The mucosal system relies on specialized cells and antibodies within the mucus-rich lining of the nose and other parts of our airways, as well as the gut. These elements move fast and arrive first, stopping the virus, SARS-CoV-2, before it can create a deep infection. “We are dealing with a different threat than we were in 2020,” says Akiko Iwasaki, an immunologist at Yale University. “If we want to contain the spread of the virus, the only way to do that is through mucosal immunity.”

Iwasaki is leading one of several research groups in the U.S. and elsewhere that are working on nasal vaccines. Some of the sprays encapsulate the coronavirus’ spike proteins—the prominent molecule that the virus uses to bind to human cells—into tiny droplets that can be puffed into the sinuses. Others add the gene for the spike to harmless versions of common viruses, such as adenoviruses, and use the defanged virus to deliver the gene into nasal tissue. Still others rely on synthetically bioengineered SARS-CoV-2 converted into a weakened form known as a live attenuated vaccine.

Sourc: https://www.scientificamerican.com/

People with obesity lost 24 kilograms on average when they were treated with the highest dose of a new hunger-blocking drug in a large clinical trial. “It’s really exciting. The weight loss they’re showing is dramatic – it’s as much as you get with successful bariatric surgery,” says Michael Cowley at Monash University in Melbourne, Australia, who wasn’t involved in the research.

The drug used, called tirzepatide, combines synthetic mimics of two hormones known as GLP-1 and GIP that our guts naturally release after we eat to make us feel full. In a late-stage clinical trial, more than 2500 people in nine countries, who weighed 105 kilograms on average at baseline, were asked to give themselves weekly injections of tirzepatide at low, medium or high doses or a placebo for 72 weeks, without knowing which one they were taking.

The highest dose of tirzepatide was most effective, resulting in 24 kilograms of weight loss on average, equivalent to a 22.5 per cent reduction in body weight. In comparison, participants taking the placebo lost just 2 kilograms on average. The results were announced on 28 April by US pharmaceutical giant Lilly, which is developing the drug.

In June 2021, the US Food and Drug Administration approved another obesity drug called semaglutide, which contains a GLP-1 mimic on its own, without the addition of GIP. Semaglutide also promotes weight loss, but by about 15 per cent on average, suggesting that the added GIP component in tirzepatide gives an extra boost, says Cowley. Like semaglutide, tirzepatide can trigger side effects such as nausea, vomiting, diarrhoea and constipation that seem worse at higher doses. However, doctors’ experience withsemaglutide has revealed that starting patients on low doses and gradually increasing them can avoid these side effects, and the same may be true for tirzepatide, says Joseph Proietto at the University of Melbourne in Australia. One advantage of obesity drugs is that they can be discontinued if necessary, says Proietto. “The downside of bariatric surgery is that you can never ever have a normal meal again, not even for a special occasion,” he says. “With medication, you can still do this.”

Source: https://www.monash.edu/
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https://www.newscientist.com/

King’s College London researchers are turning to the same technology behind the mRNA COVID-19 vaccines to develop the first damage-reversing heart attack cure. They used mRNA to deliver the genetic instructions for specific proteins to damaged pig hearts, sparking the growth of new cardiac muscle cells. “The new cells would replace the dead ones and instead of forming a scar, the patient has new muscle tissue,” lead researcher Mauro Giacca said. Researchers are turning to the same technology behind Pfizer and Moderna’s vaccines to develop the first damage-reversing heart attack cure.

Diseases of the heart are the leading cause of death around the world; the WHO estimates that 17.9 million people died from cardiovascular disease in 2019, representing almost a third of all deaths. Of those, 85% are ultimately killed by heart attacks and strokes. Heart attacks occur when blood flow to parts of the heart is blocked, often due to fat or cholesterol build up. The cardiac muscle cells — marvelous little powerhouses that keep you beating throughout your entire life — are starved of oxygen and can be damaged or killed. Left in its wake is not the smoothly pumping cardiac muscle, but instead scar tissue.

“We are all born with a set number of muscle cells in our heart and they are exactly the same ones we will die with. The heart has no capacity to repair itself after a heart attack,” explained Giacca.

At least, until now. To develop their heart attack cure, the researchers turned to mRNA, which delivers the instructions for protein creation to cells. Whereas the Pfizer and Moderna vaccines instruct cells to make the spike protein of SARS-CoV-2, priming the immune system against the virus, the same technology can deliver a potential heart attack cure by carrying the code for proteins that stimulate the growth of new heart cells, PharmaTimes reported. In an experiment with pigs (a close match for the human heart), the mRNA treatment stimulated new heart cells to grow after a heart attack — regenerating the damaged tissues and creating new, functional muscle rather than a scar.

According to BioSpace, harnessing mRNA in this way has been dubbed “genetic tracking,” named for the way the mRNA’s progress is tracked via the new proteins it is creating. The technique is being explored to create vaccines for pathogens like HIV, Ebola, and malaria, as well as cancers and autoimmune and genetic diseases. While thus far their heart attack cure has only been successfully tested in porcine pumpers, the team hopes to begin human clinical trials within the next couple years. “Regenerating a damaged human heart has been a dream until a few years ago,” Giacca said, “but can now become a reality.”

Source: https://www.freethink.com/

Renewable electricity met just shy of 100% of California’s demand for the first time on Saturday, officials said, much of it from large amounts of solar power produced along Interstate 10, an hour east of the Coachella Valley.

While partygoers celebrated in the blazing sunshine at the Stagecoach music festival,  “at 2:50 (p.m.), we reached 99.87 % of load served by all renewables, which broke the previous record,” said Anna Gonzales, spokeswoman for California Independent System Operator, a nonprofit that oversees the state’s bulk electric power system and transmission lines. Solar power provided two-thirds of the amount needed.

Environmentalists who’ve pushed for years for all of California’s power to come from renewables were jubilant as they watched the tracker edge to 100% and slightly beyond.

“California busts past 100% on this historic day for clean energy!” Dan Jacobson, senior adviser to Environment California, tweeted.

“Once it hit 100%, we were very excited,” said Laura Deehan, executive director for Environment California. She said the organization and others have worked for 20 years to push the Golden State to complete renewable power via a series of ever tougher mandates. “California solar plants play a really big role“.

But Gonzales said they doublechecked the data Monday, and had to adjust it slightly due to reserves and other resource needs.

The environmental group also pushed for 1 million solar rooftops statewide, which has been achieved, adding what some say is a more environmentally friendly form of solar power than the solar farms, which eat up large swaths of the Mojave desert and fragile landscapes.

Source: https://eu.usatoday.com/