Blood Cancer Therapy Successful in 75% of Trial Patients

New data from an ongoing Phase 1/2 clinical trial has revealed an experimental immunotherapy led to successful response rates in 73% of patients suffering from multiple myeloma, a deadly form of blood cancer. Based on this promising data, an application to the US Food and Drug Administration (FDA) has been filed to bring the drug to market.

 

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How to Detect Diabetes Early Enough To Reverse It

Diabetes is a severe and growing metabolic disorder. It already affects hundreds of thousands of people in Switzerland. A sedentary lifestyle and an excessively rich diet damage the beta cells of the pancreas, promoting the onset of this disease. If detected early enough, its progression could be reversed, but diagnostic tools that allow for early detection are lacking. A team from the University of Geneva (UNIGE) in collaboration with several other scientists, including teams from the HUG, has discovered that a low level of the sugar 1,5-anhydroglucitol in the blood is a sign of a loss in functional beta cells. This molecule, easily identified by a blood test, could be used to identify the development of diabetes in people at risk, before the situation becomes irreversible. These results can be found in the Journal of Clinical Endocrinology & Metabolism.
In Switzerland, almost 500,000 people suffer from diabetes. This serious metabolic disorder is constantly increasing due to the combined effect of a lack of physical activity and an unbalanced diet. If detected early enough at the pre-diabetes stage, progression to an established diabetes can be counteracted by adopting an appropriate lifestyle. Unfortunately, one third of patients already have cardiovascular, renal or neuronal complications at the time of diagnosis, which impacts their life expectancy.

When diabetes starts to develop but no symptoms are yet detectable, part of the beta cells of the pancreas (in green) disappear (right image) compared to a healthy individual (left image). This previously undetectable decrease could be identified by measuring the level of 1,5-anhydroglucitol in the blood

‘‘Identifying the transition from pre-diabetes to diabetes is complex, because the status of the affected cells, which are scattered in very small quantities in the core of an organ located under the liver, the pancreas, is impossible to assess quantitatively by non-invasive investigations. We therefore opted for an alternative strategy: to find a molecule whose levels in the blood would be associated with the functional mass of these beta cells in order to indirectly detect their alteration at the pre-diabetes stage, before the appearance of any symptoms,’’ explains Pierre Maechler, a Professor in the Department of Cell Physiology and Metabolism and in the Diabetes Centre of the UNIGE Faculty of Medicine, who led this work.

Several years ago, scientists embarked on the identification of such a molecule able to detect pre-diabetes. The first step was to analyse thousands of molecules in healthy, pre-diabetic and diabetic mouse models. By combining powerful molecular biology techniques with a machine learning system (artificial intelligence), the research team was able to identify, from among thousands of molecules, the one that best reflects a loss of beta cells at the pre-diabetic stage: namely 1,5-anhydroglucitol, a small sugar, whose decrease in blood would indicate a deficit in beta cells.

Source: https://www.unige.ch/

Saudi Arabia to Spend $1 billion a Year to Slow Aging

Anyone who has more money than they know what to do with eventually tries to cure aging. Google founder Larry Page has tried it. Jeff Bezos has tried it. Tech billionaires Larry Ellison and Peter Thiel have tried it. Now the kingdom of Saudi Arabia, which has about as much money as all of them put together, is going to try it. The Saudi royal family has started a not-for-profit organization called the Hevolution Foundation that plans to spend up to $1 billion a year of its oil wealth supporting basic research on the biology of aging and finding ways to extend the number of years people live in good health, a concept known as “health span.”

The sum, if the Saudis can spend it, could make the Gulf state the largest single sponsor of researchers attempting to understand the underlying causes of aging—and how it might be slowed down with drugs. The foundation hasn’t yet made a formal announcement, but the scope of its effort has been outlined at scientific meetings and is the subject of excited chatter among aging researchers, who hope it will underwrite large human studies of potential anti-aging drugs. The fund is managed by Mehmood Khan, a former Mayo Clinic endocrinologist and the onetime chief scientist at PespsiCo, who was recruited to the CEO job in 2020. ““Our primary goal is to extend the period of healthy lifespan,” Khan said in an interview. “There is not a bigger medical problem on the planet than this one.

The idea, popular among some longevity scientists, is that if you can slow the body’s aging process, you can delay the onset of multiple diseases and extend the healthy years people are able to enjoy as they grow older. Khan says the fund is going to give grants for basic scientific research on what causes aging, just as others have done, but it also plans to go a step further by supporting drug studies, including trials of “treatments that are patent expired or never got commercialized.”

We need to translate that biology to progress towards human clinical research. Ultimately, it won’t make a difference until something appears in the market that actually benefits patients,” Khan says.

Khan says the fund is authorized to spend up to $1 billion per year indefinitely, and will be able to take financial stakes in biotech companies. By comparison, the division of the US National Institute on Aging that supports basic research on the biology of aging spends about $325 million a year.

Hevolution hasn’t announced what projects it will back, but people familiar with the group say it looked at funding a $100 million X Prize for age reversal technology and has reached a preliminary agreement to fund a test of the diabetes drug metformin in several thousand elderly people.

That trial, known as “TAME” (for “Targeting Aging with Metformin”), has been touted as the first major test of any drug to postpone aging in humans, but the study has languished for years without anyone willing to pay for it.

Source: https://www.technologyreview.com/

Are Contact Lenses the Ultimate Computer Screen?

Imagine you have to make a speech, but instead of looking down at your notes, the words scroll in front of your eyes, whichever direction you look in. That’s just one of many features the makers of smart contact lenses promise will be available in the future.

Imagine… you’re a musician with your lyrics, or your chords, in front of your eyes. Or you’re an athlete and you have your biometrics and your distance and other information that you need,” says Steve Sinclair, from Mojo, which is developing smart contact lenses.
His company is about to embark on comprehensive testing of smart contact lens on humans, that will give the wearer a heads-up display that appears to float in front of their eyes.

The product’s scleral lens (a larger lens that extends to the whites of the eye) corrects the user’s vision, but also incorporates a tiny microLED display, smart sensors and solid-state batteries. “We’ve built what we call a feature-complete prototype that actually works and can be worn – we’re soon going to be testing that [out] internally,” says Mr Sinclair. “Now comes the interesting part, where we start to make optimisations for performance and power, and wear it for longer periods of time to prove that we can wear it all day.”

Other smart lenses are being developed to collect health data. Lenses could “include the ability to self-monitor and track intra-ocular pressure, or glucose,” says Rebecca Rojas, instructor of optometric science at Columbia University. Glucose levels for example, need to be closely monitored by people with diabetes. “They can also provide extended-release drug-delivery options, which is beneficial in diagnosis and treatment plans. It’s exciting to see how far technology has come, and the potential it offers to improve patients’ lives.

Research is underway to build lenses that can diagnose and treat medical conditions from eye conditions, to diabetes, or even cancer by tracking certain biomarkers such as light levels, cancer-related molecules or the amount of glucose in tears. A team at the University of Surrey, for example, has created a smart contact lens that contains a photo-detector for receiving optical information, a temperature sensor for diagnosing potential corneal disease and a glucose sensor monitoring the glucose levels in tear fluid.

Source: https://www.bbc.com/

New Drug Could Protect Against Aging

Senolytics are an emerging class of drugs designed to target zombie-like cells that have stopped dividing and build up in the body as we age, and the past few years have seen some exciting discoveries that demonstrate their potential. Adding another to the list are Mayo Clinic researchers, who have shown that these drugs can protect against aging and its related diseases, by acting on a protein long associated with longevity. The zombie-like cells involved in this research are known as senescent cells, and their accumulation during aging is associated with a range of diseases. Recent studies have shown that using senolytics to clear them out could serve as new and effective treatments for dementia and diabetes, and also improve health and lifespan more broadly.

The Mayo Clinic team were exploring how senolytics can influence levels of a protein called a-klotho, known to help protect older people from the effects of aging. The role of this protein in the aging process is well established and has placed it at the center of much research in this space, with studies demonstrating how it could help reverse osteoarthritis and regenerate old musclesLevels of a-klotho are also known to decrease with age, and studies have shown these declines shorten the lifespan of mice. Conversely, inserting genes that encode for the protein has been shown to increase the lifespan of mice by 30 percent. Boosting its levels in humans has been problematic, however, as its larger size would require it to be administered intravenously. But now the Mayo Clinic scientists believe they have found another route, as senolytic drugs can be administered orally.

They first showed that senescent cells reduce levels of a-klotho in human cells. They then demonstrated that using a combination of senolytic drugs on three different types of mice could counter this and increase levels of a-klotho. This effect was then observed in follow-up experiments on patients with idiopathic pulmonary fibrosis, a lung disease that can cause breathing difficulty, frailty and death.

“We show that there is an avenue for an orally active, small-molecule approach to increase this beneficial protein and also to amplify the action of senolytic drugs,” says James Kirkland, M.D., Ph.D., a Mayo Clinic internist and senior author of the study.

Source: https://www.thelancet.com/

Could Sound Replace Pacemakers and Insulin Pumps?

Imagine a future in which crippling epileptic seizures, faltering hearts and diabetes could all be treated not with scalpels, stitches and syringes, but with sound. Though it may seem the stuff of science fiction, a new study shows that this has solid real-world potential.

Sonogenetics – the use of ultrasound to non-invasively manipulate neurons and other cells – is a nascent field of study that remains obscure amongst non-specialists, but if it proves successful it could herald a new era in medicine.

In the new study published in Nature Communications, researchers from the Salk Institute for Biological Studies in California, US, describe a significant leap forward for the field, documenting their success in engineering mammalian cells to be activated using ultrasound. The team say their method, which they used to activate human cells in a dish and brain cells inside living mice, paves the way toward non-invasive versions of deep brain stimulation, pacemakers and insulin pumps.

Going wireless is the future for just about everything,” says senior author Dr Sreekanth Chalasani, an associate professor in Salk’s Molecular Neurobiology Laboratory. “We already know that ultrasound is safe, and that it can go through bone, muscle and other tissues, making it the ultimate tool for manipulating cells deep in the body.

Chalasani is the mastermind who first established the field of sonogenetics a decade ago. He discovered that ultrasound sound waves beyond the range of human hearing — can be harnessed to control cells. Since sound is a form of mechanical energy, he surmised that if brain cells could be made mechanically sensitive, then they could be modified with ultrasound.

In 2015 his research group provided the first successful demonstration of the theory, adding a protein to cells of a roundworm, Caenorhabditis elegans, that made them sensitive to low-frequency ultrasound and thus enabled them to be activated at the behest of researchers.

Chalasani and his colleagues set out to search for a new protein that would work in mammals. Although a few proteins were already known to be ultrasound sensitive, no existing candidates were sensitive at the clinically safe frequency of 7MHz – so this was where the team set their sights. To test whether TRPA1 protein could activate cell types of clinical interest in response to ultrasound, the team used a gene therapy approach to add the genes for human TRPA1 to a specific group of neurons in the brains of living mice. When they then administered ultrasound to the mice, only the neurons with the TRPA1 genes were activated.

Clinicians treating conditions including Parkinson’s disease and epilepsy currently use deep brain stimulation, which involves surgically implanting electrodes in the brain, to activate certain subsets of neurons. Chalasani says that sonogenetics could one day replace this approach—the next step would be developing a gene therapy delivery method that can cross the blood-brain barrier, something that is already being studied. Perhaps sooner, he says, sonogenetics could be used to activate cells in the heart, as a kind of pacemaker that requires no implantation.

Source: https://www.salk.edu/
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https://cosmosmagazine.com/

Higher Risk of Dementia for Millions with Eye Conditions

Millions of people with eye conditions including age-related macular degeneration, cataracts and diabetes-related eye disease have an increased risk of developing dementia, new research shows. Vision impairment can be one of the first signs of the disease, which is predicted to affect more than 130 million people worldwide by 2050.

Previous research has suggested there could be a link between eye conditions that cause vision impairment, and cognitive impairment. However, the incidence of these conditions increases with age, as do systemic conditions such as diabetes, high blood pressure, heart disease, depression and stroke, which are all accepted risk factors for dementia. That meant it was unclear whether eye conditions were linked with a higher incidence of dementia independently of systemic conditions.

Now researchers have found that age-related macular degeneration, cataracts and diabetes-related eye disease are independently associated with increased risk of dementia, according to a new study published in the British Journal of Ophthalmology.

The research examined data from 12,364 British adults aged 55 to 73, who were taking part in the UK Biobank study. They were assessed in 2006 and again in 2010 with their health information tracked until early 2021. More than 2,300 cases of dementia were documented, according to the international team of experts led by academics from the Guangdong Eye Institute in China. After assessing health data, researchers found those with age-related macular degeneration had a 26% increased risk of developing dementia. Those with cataracts had an 11% increased risk and people with diabetes-related eye disease had a 61% heightened risk. Glaucoma was not linked to a significant increase in risk.

Researchers also found that people with conditions including diabetes, heart disease, stroke and depression were also more likely to be diagnosed with dementia. Risk was highest among people with one of these conditions who also had some form of eye condition, they said.

Age-related macular degeneration, cataract and diabetes-related eye disease but not glaucoma are associated with an increased risk of dementia,” the authors concluded.

Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.”

The study comes as Alzheimer’s Research UK says public willingness to get involved with medical research is at an “all-time high”. The charity said 29% of adults were more likely to consider getting involved in medical research because of the pandemic, according to a poll of 1,000 adults across England, Scotland and Wales.

The survey found that 69% said they would be willing to get involved with dementia research, compared with 50% of a sample of people from a year ago.

This is positive news for the thousands of studies waiting to get under way to help understand and tackle health conditions like dementia, cancer, and heart disease,” said Hilary Evans, the chief executive of Alzheimer’s Research UK.

Source: https://www.theguardian.com/

Anti-diabetic Medication at a Specific Dosage Makes you Loose Weight

A weight-loss drug described as a ‘game-changer by obesity researchers has just been approved by the US Food and Drug Administration (FDA), representing the first time the agency has endorsed such a treatment in several years. Wegovy, a weight-management therapy to be manufactured by Danish pharmaceutical company Novo Nordisk, is the the first FDA-approved weight-loss drug since 2014, but it’s not entirely a new medication.

The same drug, called semaglutide, has been used in the US and other countries as an anti-diabetic medication for years. More recently, however, evidence has shown that semaglutide at a different dosage also functions as a powerful and effective appetite-suppressant. In a study published earlier in the year involving almost 2,000 obese adults from 16 different countries, researchers reported that long-term treatment with the medicine led to almost 15 percent weight loss on average across the cohort.

Some lost even more, with over 30 percent of the group dropping in excess of 20 percent of their body weight – results that the scientists singled out as remarkable.

No other drug has come close to producing this level of weight loss – this really is a game-changer,” obesity researcher Rachel Batterham from University College London said at the time.

For the first time, people can achieve through drugs what was only possible through weight-loss surgery.”

Source: https://www.sciencealert.com/

How To Reverse Aging in the Brain

The aging global population is the greatest challenge faced by 21st-century healthcare systems. Even COVID-19 is, in a sense, a disease of aging. The risk of death from the virus roughly doubles for every nine years of life, a pattern that is almost identical to a host of other illnesses. But why are old people vulnerable to so many different things?

It turns out that a major hallmark of the aging process in many mammals is inflammation. By that, I don’t mean intense local response we typically associate with an infected wound, but a low grade, grinding, inflammatory background noise that grows louder the longer we live. This “inflammaging” has been shown to contribute to the development of atherosclerosis (the buildup of fat in arteries), diabetes, high blood pressure , frailty, cancer and cognitive decline.

Now a new study published in Nature reveals that microglia — a type of white blood cells found in the brain — are extremely vulnerable to changes in the levels of a major inflammatory molecule called prostaglandin E2 (PGE2). The team found that exposure to this molecule badly affected the ability of microglia and related cells to generate energy and carry out normal cellular processes.

Fortunately, the researchers found that these effects occurred only because of PGE2’s interaction with one specific receptor on the microglia. By disrupting it, they were able to normalize cellular energy production and reduce brain inflammation. The result was improved cognition in aged mice. This offers hope that the cognitive impairment associated with growing older is a transient state we can potentially fix, rather than the inevitable consequence of aging of the brain. Levels of PGE2 increase as mammals age for a variety of reasons — one of which is probably the increasing number of cells in different tissues entering a state termed cellular senescence. This means they become dysfunctional and can cause damage to tissue by releasing PGE2 and other inflammatory molecules.

But the researchers also found that macrophages — another type of white blood cells related to microglia — from people over the age of 65 made significantly more PGE2 than those from young people. Intriguingly, exposing these white blood cells to PGE2 suppressed the ability of their mitochondria — the nearest thing a cell has to batteries — to function. This meant that the entire pattern of energy generation and cellular behavior was disrupted.

Although PGE2 exerts its effects on cells through a range of receptors, the team were able to narrow down the effect to interaction with just one type (the “EP2 receptor” on the macrophages). They showed this by treating white blood cells, grown in the lab, with drugs that either turned this receptor on or off. When the receptor was turned on, cells acted as if they had been exposed to PGE2. But when they were treated with the drugs that turned it off, they recovered. That’s all fine, but it was done in a petri dish. What would happen in an intact body?

The researchers took genetically modified animals in which the EP2 receptor had been removed and allowed them to grow old. They then tested their learning and memory by looking at their ability to navigate mazes (something of a cliche for researchers) and their behavior in an “object location test.” This test is a bit like someone secretly entering your house, swapping your ornaments around on the mantelpiece and then sneaking out again. The better the memory, the longer the subject will spend looking suspiciously at the new arrangement, wondering why it has changed.

It turned out that the old genetically modified mice learned and remembered just as well as their young counterparts. These effects could be duplicated in normal old mice by giving them one of the drugs that could turn the EP2 receptor off for one month. So it seems possible that inhibiting the interaction of PGE2 with this particular receptor may represent a new approach to treating late-life cognitive disorders.

Source: https://www.theconversation.com/

Immune System Killer Cells Controlled By Circadian Rhythms

An analysis of an exhaustive dataset on cells essential to the mammalian immune system shows that our ability to fight disease may rely more heavily on daily circadian cycles than previously assumed.

Malfunctions in , the process that keeps our bodies in tune with the day/night cycles, are increasingly associated with diabetes, cancer, Alzheimer’s, and many other diseases. An investigation published today in Genome Research shows that the activity of macrophagescells within us that seek and destroy intruders like bacteria—may time daily changes in their responses to pathogens and stress through the circadian control of metabolism. In this study, Jennifer Hurley, the Richard Baruch M.D. Career Development Assistant Professor of Biological Sciences at Rensselaer Polytechnic Institute and senior author on this study, and her team investigated how the levels of RNA and proteins in macrophages change over two days.

We have shown there is an incredible amount of circadian timing of macrophage behavior, but the clock is timing macrophages in unexpected ways” said Hurley.

The circadian system is comprised of a set of core clock proteins that anticipate the day/night cycle by causing daily oscillations in levels of enzymes and hormones, and ultimately affecting physiological parameters such as body temperature and the immune response. This molecular clock marks time through a self-regulating cycle of  production and decay. The “positive” element proteins of the clock trigger production of the “negative” element proteins, which in turn block production of positive element proteins until the negative element proteins decay, thus creating a negative feedback cycle that occurs once every 24 hours.

Positive element proteins also regulate fluctuations in a substantial number of gene products, known as messenger RNA or mRNA. Genetic instructions are transcribed from DNA to mRNA, which are then used as a recipe for assembling proteins, the functional building blocks of the cell. It has long been assumed that the levels of each subsequent step could be predicted from the previous. If that were the case, oscillating mRNA would correspond with oscillating levels of cellular proteins, and therefore, if one could track mRNA, they would know what proteins the circadian clock controlled in the cell.

However, this investigation showed that this paradigm may not always be true. The analysis of the macrophage dataset revealed that there was a substantial mismatch between the proteins and mRNAs that are controlled by the circadian clock. This data paralleled research published in Cell Systems in 2018 by the Hurley lab, showing that about 40% of oscillating proteins in the fungus and circadian model system, Neurospora crassa, had no corresponding oscillating mRNA.

But the scale of the difference in macrophages really surprised us,” Hurley said. “Eighty percent of the proteins that oscillate don’t have associated oscillating mRNA in macrophages. That means we were really missing how the clock was timing immunity.”

Source: https://medicalxpress.com/