March 23, 2023
|
Posted by admin
Terminal leukaemia patients who were not responding to treatment now have hope for a cure, thanks to a new experimental pill called revumenib. This drug has completely eliminated cancer in a third of the participants in a long-awaited clinical trial in the United States. Although not all patients showed complete remission, scientists remain hopeful as the results indicate that the pill might pave the way to a cure for leukaemia in the future.
“We’re incredibly hopeful by these results of patients that received this drug. This was their last chance,” said study co-author Dr Ghayas Issa, a leukaemia physician at the MD Anderson Cancer Center at the University of Texas. “They have progressed on multiple lines of therapy and a fraction of them, about half, had disappearance of their leukaemia cells from their bone marrow,” he told Euronews Next.
Acute myeloid leukaemia (AML) is a type of cancer that attacks the bone marrow, where blood cells are produced, and causes the uncontrolled production of defective cells. Revumenib is a new class of targeted therapy for acute leukaemia that inhibits a specific protein called menin. The drug works by reprogramming leukaemia cells back into normal cells. Menin is involved in the complex machinery that gets hijacked by leukaemia cells and causes normal blood cells to turn into cancerous ones. By using revumenib, Issa explained, the engine is turned off and leukaemia cells are turned back into normal cells, resulting in remission.
This formula has already saved 18 lives as part of the clinical trial, whose promising results were published this month in Nature. The preliminary results showed that 53 per cent of patients responded to revumenib, and 30 per cent had a complete remission with no cancer detectable in their blood. Based on the data from this trial, in December 2022 the US Food and Drug Administration granted revumenib “breakthrough therapy designation” to help fast-track its development and regulatory review.
“This is definitely a breakthrough and it’s a result of years of science. A lot of groups had worked hard in the lab to understand what is causing these leukaemias,” Issa said. However, he explained that the drug does not work for all patients. It is for a specific subset of leukaemias that generally have missing or mislabeled genes or a chromosome fusion. The experimental pill targets the most common mutation in acute myeloid leukaemia, a gene called NPM1, and a less common fusion called KMT2A. Combined, these mutations are estimated to occur in about 30 to 40 per cent of people with acute myeloid leukaemia.
The phase 1 trial enrolled 68 patients at nine US hospitals. All of them had seen their leukaemia return after other treatments or had never responded well to traditional chemotherapy drugs in the first place.
Source: https://www.euronews.com/next/
Categories: Uncategorized
| 
Tags: Acute myeloid leukaemia, AML, bone marrow, cancer, cells, drug, Food and Drug Administratio, gene, KMT2A, leukaemia, Menin, NPM1, pill, protein, remission, revumenib, University of Texas
March 20, 2023
|
Posted by admin
In less than a month, researchers have used AlphaFold, an artificial intelligence (AI)-powered protein structure database, to design and synthesize a potential drug to treat hepatocellular carcinoma (HCC), the most common type of primary liver cancer. The researchers successfully applied AlphaFold to an end-to-end AI-powered drug discovery platform called Pharma.AI. That included a biocomputational engine, PandaOmics, and a generative chemistry engine, Chemistry42. They discovered a novel target for HCC – a previously undiscovered treatment pathway – and developed a “novel hit molecule” that could bind to that target without the aid of an experimentally determined structure. The feat was accomplished in just 30 days from target selection and after only synthesizing seven compounds.
In a second round of AI-powered compound generation, researchers discovered a more potent hit molecule – although any potential drug would still need to undergo clinical trials. The study – published in Chemical Science – is led by the University of Toronto Acceleration Consortium Director Alán Aspuru-Guzik, Nobel laureate Michael Levitt and Insilico Medicine founder and CEO Alex Zhavoronkov.
“While the world was fascinated with advances in generative AI in art and language, our generative AI algorithms managed to design potent inhibitors of a target with an AlphaFold-derived structure,” Zhavoronkov said. “AlphaFold broke new scientific ground in predicting the structure of all proteins in the human body,” added co-author Feng Ren, chief scientific officer and co-CEO of Insilico Medicine. “At Insilico Medicine, we saw that as an incredible opportunity to take these structures and apply them to our end-to-end AI platform in order to generate novel therapeutics to tackle diseases with high unmet need. This paper is an important first step in that direction.”
Source: https://www.utoronto.ca/
AND
https://www.dailymail.co.uk/
Categories: Uncategorized
| Tags: AI, AlphaFold, Artificial Intelligence, Chemistry42, drug, HCC, hepatocellular carcinoma, Insilico Medicine, liver cancer, PandaOmics, Pharma.AI, protein structure database, University of Toronto, University of Toronto Acceleration Consortium
February 23, 2023
|
Posted by admin
Israeli scientists gave an artificial molecule they invented to 30 mice suffering from Alzheimer’s — and found that all of them recovered, regaining full cognitive abilities. They stress that this was a small sample of mice and that human testing is far off, but believe the result indicates that within a decade, their synthetic molecule could be developed into a drug for treating the degenerative disease. The peer-reviewed research, led by neuroscientists from Ben-Gurion University, was recently published in the journal Translational Neurodegeneration.
“We are taking a very different approach than efforts at Alzheimer’s medicines that we have seen so far,” Prof. Varda Shoshan-Barmatz, the lead author, told The Times of Israel. “Most are trying to address plaque that forms in the brain, but we are addressing dysfunction elsewhere. And we’re optimistic. Mice who had Alzheimer’s and received our molecule and then underwent tests had the same cognitive abilities as mice who’d never had Alzheimer’s.”
Interestingly, the molecule appears to have been effective without significantly reducing the amount of plaque, which she thinks indicates that scientists may have been overly fixated on the plaque. There is scientific literature on the dysfunction of mitochondria among people with Alzheimer’s. Mitochondria are organelles — tiny miniature organs within cells — that provide the cell with power. Scientists believe that when they malfunction and fail to produce the normal quantities of energy, it can lead to cell death, inflammation and reduced immune response.
Despite Alzheimer’s being linked to mitochondrial dysfunction, no drug candidates are currently focused on mitochondria. Drug research is mostly concerned with combatting the buildup of protein fragments between nerve cells in the brain, which are thought to be linked to Alzheimer’s. The Ben-Gurion University team set out to normalize mitochondrial activity by countering the harmful effects that occur when a protein called VDAC1 is over-produced. The protein plays a crucial role in regulating the metabolic and energetic functions of mitochondria when produced in normal quantities. But the scientists found that it is produced in huge levels in the brains of mice with Alzheimer’s, and interferes with mitochondrial activity.
“In our research, we have shifted the focus of Alzheimer’s treatments from the plaque to this protein, which is produced in the nerve cells around the plaque instead,” said Shoshan-Barmatz. “We prevent this protein from causing cell death, as the molecule interferes with its harmful effect.”
Source: https://in.bgu.ac.il/
AND
https://www.timesofisrael.com/
Categories: Uncategorized
| Tags: Alzheimer's, artificial molecule, Ben-Gurion University, brain, cell, cognitive abilities, degenerative disease, drug, immune response, inflammation, mitochondria, nerve cells, organelles, plaque, protein, Translational Neurodegeneration, VDAC1
October 31, 2022
|
Posted by admin
Biomedical engineers at Duke University have demonstrated the most effective treatment for pancreatic cancer ever recorded in mouse models. While most mouse trials consider simply halting growth a success, the new treatment completely eliminated tumors in 80 percent of mice across several model types, including those considered the most difficult to treat. 
The approach combines traditional chemotherapy drugs with a new method for irradiating the tumor. Rather than delivering radiation from an external beam that travels through healthy tissue, the treatment implants radioactive iodine-131 directly into the tumor within a gel-like depot that protects healthy tissue and is absorbed by the body after the radiation fades away.
You must be logged in to view this content.
Categories: Uncategorized
| Tags: beam, Cereius, chemotherapy, chemotherapy drugs, drug, Duke University, gel, irradiation, mutations, pancreatic cancer, radioactive iodine-131, titanium, tumors
September 9, 2022
|
Posted by admin
Treatment of cancer is a long-term process because remnants of living cancer cells often evolve into aggressive forms and become untreatable. Hence, treatment plans often involve multiple drug combinations and/or radiation therapy in order to prevent cancer relapse. To combat the variety of cancer cell types, modern drugs have been developed to target specific biochemical processes that are unique within each cell type.
However, cancer cells are highly adaptive and able to develop mechanisms to avoid the effects of the treatment.
“We want to prevent such adaptation by invading the main pillar of cellular life—how cells breathe—that means take up oxygen—and thus produce chemical energy for growth,” says David Ng, group leader at the MPI-P.
The research team produced a synthetic drug that travels into cells where it reacts to conditions found inside and triggers a chemical process. This allows the drug’s molecules to bind together and form tiny hairs that are a thousand times thinner than human hair. “These hairs are fluorescent, so you can look at them directly with a microscope as they form,” says Zhixuan Zhou, an Alexander-von-Humboldt-fellow and first author of the paper.
The scientists monitored the oxygen consumption in different cell types and found that the hairs stop all of them from converting oxygen into ATP, a molecule that is responsible for energy delivery in cells. The process worked even for those cells derived from untreatable metastatic cancer. As a result, the cells die rapidly within four hours. After some more years of research, the scientists hope that they can develop a new method to treat up-to-now untreatable cancer.
Weil, Ng and colleagues have shown an exciting outcome under controlled laboratory culture and will continue to unravel deeper insights on the basis of how these tiny hairs prevent the conversion of oxygen to chemical energy. With further development, these objects could in the future possibly also be manipulated to control other cellular processes to address other important diseases.
They have published their results in the Journal of the American Chemical Society.
Source: https://phys.org/
Categories: Uncategorized
| Tags: Alexander-von-Humboldt, ATP, cancer, cancerous cells, drug, energy, oxygen consumption, radiation therapy, relapse, untreatable metastatic cancer
August 12, 2022
|
Posted by admin
A University of Minnesota (U OF M) Twin Cities-led team has found that electrical stimulation of the body combined with sound activates the brain’s somatosensory or “tactile” cortex, increasing the potential for using the technique to treat chronic pain and other sensory disorders. The researchers tested the non-invasive technique on animals and are planning clinical trials on humans in the near future. During the study, published in the Journal of Neural Engineering, the researchers played broadband sound while electrically stimulating different parts of the body in guinea pigs. They found that the combination of the two activated neurons in the brain’s somatosensory cortex, which is responsible for touch and pain sensations throughout the body.
While the researchers used needle stimulation in their experiments, one could achieve similar results using electrical stimulation devices, such as nerve stimulation (TENS) units, which are widely available. The researchers hope that their findings will lead to a treatment for chronic pain that’s safer and more accessible than drug approaches.
“Chronic pain is a huge issue for a lot of people, and for most, it’s not sufficiently treatable,” said Cory Gloeckner, lead author on the paper, a Ph.D. alumnus of the U of M Department of Biomedical Engineering and an assistant professor at John Carroll University. “Right now, one of the ways that we try to treat pain is opioids, and we all know that doesn’t work out well for many people. This, on the other hand, is a non-invasive, simple application. It’s not some expensive medical device that you have to buy in order to treat your pain. It’s something that we think would be available to pretty much anyone because of its low cost and simplicity.”
The researchers plan to continue investigating this “multimodal” approach to treating different neurological conditions, potentially integrating music therapy in the future to see how they can further modify the somatosensory cortex.
Source: https://twin-cities.umn.edu/
Categories: Uncategorized
| Tags: brain’s somatosensory, broadband sound, chronic pain, cortex, drug, electric stimulation, Electrical Stimulation, John Carroll University., music therapy, nerve, sound, tactile, TENS, U of M, University of Minnesota
July 20, 2022
|
Posted by admin
A revolutionary new treatment for cataracts has shown extremely positive results in laboratory tests, giving hope that the condition, that currently can only be cured with surgery, could soon be treated with drugs.
According to the World Health Organization (WHO), 65.2 million people worldwide are living with cataracts, the leading cause of blindness and vision impairment worldwide. Cataract is a clouding of the eye lens that is caused by a disorganisation of the proteins in the lens that leads to clumps of protein forming that scatter light and severely reduce transmission to the retina. This often occurs with age, but can also be caused by the eye’s overexposure to the sun or injury, as well as smoking, medical conditions such as diabetes, and some medications.
Surgery can correct the condition by replacing the lens with an artificial one. A team of international scientists, led by Professor Barbara Pierscionek, Deputy Dean (Research and Innovation) in the Faculty of Health, Education, Medicine and Social Care at Anglia Ruskin University (ARU), have been carrying out advanced optical tests on an oxysterol compound that had been proposed as an anti-cataract drug.
The compound oxysterol, is an oxygenated derivative of cholesterol that plays a role in the regulation and transport of cholesterol. This means that the protein organisation of the lens is being restored, resulting in the lens being better able to focus. This was supported by a reduction in lens opacity in 46% of cases.
The researchers tested an assortment of 35 wild mice and mice genetically altered to develop lens cloudiness through an alteration of their αB-crystallin or αA-crystallin proteins. In the right eye of 26 mice, the researchers administered a single drop of an oxysterol compound, VP1-001Trusted Source, directly onto the ocular surface. Meanwhile, they gave a neutral drop of cyclodextrin in their left eyes. Nine mice were left untreated as a control group. The target of the treatment was the αA- and αB-crystallin mutations that often cause cataracts in aging.
The results have been published today in the peer-reviewed journal Investigative Ophthalmology and Visual Science.
Source: https://aru.ac.uk/
and
https://www.thebrighterside.news/
Categories: Uncategorized
| Tags: Anglia Ruskin University, anti-cataract drug, ARU, blindness, cataract, cholesterol, drug, lens, oxysterol, retina, αA-crystallin proteins, αB-crystallin
July 15, 2022
|
Posted by admin
The entirety of the known universe is teeming with an infinite number of molecules. But what fraction of these molecules have potential drug-like traits that can be used to develop life-saving drug treatments? Millions? Billions? Trillions? The answer: novemdecillion, or 1060. This gargantuan number prolongs the drug development process for fast-spreading diseases like Covid-19 because it is far beyond what existing drug design models can compute. To put it into perspective, the Milky Way has about 100 billion, or 1011, stars.
In a paper that will be presented at the International Conference on Machine Learning (ICML), MIT researchers developed a geometric deep-learning model called EquiBind that is 1,200 times faster than one of the fastest existing computational molecular docking models, QuickVina2-W, in successfully binding drug-like molecules to proteins. EquiBind is based on its predecessor, EquiDock, which specializes in binding two proteins using a technique developed by the late Octavian-Eugen Ganea, a recent MIT Computer Science and Artificial Intelligence Laboratory and Abdul Latif Jameel Clinic for Machine Learning in Health (Jameel Clinic) postdoc, who also co-authored the EquiBind paper.
Before drug development can even take place, drug researchers must find promising drug-like molecules that can bind or “dock” properly onto certain protein targets in a process known as drug discovery. After successfully docking to the protein, the binding drug, also known as the ligand, can stop a protein from functioning. If this happens to an essential protein of a bacterium, it can kill the bacterium, conferring protection to the human body.
However, the process of drug discovery can be costly both financially and computationally, with billions of dollars poured into the process and over a decade of development and testing before final approval from the Food and Drug Administration. What’s more, 90 percent of all drugs fail once they are tested in humans due to having no effects or too many side effects. One of the ways drug companies recoup the costs of these failures is by raising the prices of the drugs that are successful.
The current computational process for finding promising drug candidate molecules goes like this: most state-of-the-art computational models rely upon heavy candidate sampling coupled with methods like scoring, ranking, and fine-tuning to get the best “fit” between the ligand and the protein.
EquiBind (cyan) predicts the ligand that could fit into a protein pocket (green). The true conformation is in pink.
Hannes Stärk, a first-year graduate student at the MIT Department of Electrical Engineering and Computer Science and lead author of the paper, likens typical ligand-to-protein binding methodologies to “trying to fit a key into a lock with a lot of keyholes. ” Typical models time-consumingly score each “fit” before choosing the best one. In contrast, EquiBind directly predicts the precise key location in a single step without prior knowledge of the protein’s target pocket, which is known as “blind docking.”
Unlike most models that require several attempts to find a favorable position for the ligand in the protein, EquiBind already has built-in geometric reasoning that helps the model learn the underlying physics of molecules and successfully generalize to make better predictions when encountering new, unseen data.
Source: https://news.mit.edu/
Categories: Uncategorized
| Tags: drug, EquiDock, FDA, ligand, MIT
June 17, 2022
|
Posted by admin
Many cancer treatments are notoriously savage on the body; they attack healthy cells at the same time as tumor cells, causing a plethora of side effects. Now, researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have designed a method to keep one promising cancer drug from wreaking such havoc. The team has engineered a new “masked” version of the immunotherapy drug interleukin-12 that is activated only when it reaches a tumor.
Researchers have long suspected that interleukin-12 could be a powerful cancer treatment, but it caused dangerous side effects. Now, Pritzker Molecular Engineering researchers have developed a version of the molecule not activated until it reaches a tumor, where it eradicates cancer cells.
“Our research shows that this masked version of IL-12 is much safer for the body, but it possesses the same anti-tumor efficacy as the original,” said Aslan Mansurov, a postdoctoral research fellow and first author of the new paper. He carried out the IL-12 engineering work with Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering, who co-leads PME’s Immunoengineering research theme with professor Melody Swartz.
Researchers know that IL-12 potently activates lymphocytes, immune cells with the potential to destroy tumor cells. But, in the 1990s, early clinical trials of IL-12 were halted because of severe, toxic side effects in patients. The same immune activation that started a cascade of events killing cancer cells also led to severe inflammation throughout the body. IL-12, at least in its natural form, was shelved.
The research on the molecule, also known as IL-12, is described in the journal Nature Biomedical Engineering.
But Mansurov, Hubbell, Swartz, and colleagues had an idea to reinvigorate the possibility of IL-12. What if the drug could slip through the body without activating the immune system? They designed a “masked” molecule with a cap covering the section of IL-12 which normally binds immune cells. The cap can be removed only by tumor-associated proteases, a set of molecular scissors found in the vicinity of tumors to help them degrade surrounding healthy tissue. When the proteases chop off the cap, the IL-12 becomes active, able to spur an immune response against the tumor.
“The masked IL-12 is largely inactive everywhere in the body except at the site of the tumor, where these proteases can cleave off the mask,” explained Mansurov.
Source: https://pme.uchicago.edu/
Categories: Uncategorized
| Tags: cancer, drug, healthy cells, IL-12, immune cells, immunotherapy drug, interleukin-12, lymphocytes, molecule, PME, side effects, tumor, tumor cells, University of Chicago
June 8, 2022
|
Posted by admin
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.
Source: https://www.technologyreview.com/
Categories: Uncategorized
| Tags: aging, diabetes, drug, health span, Hevolution Foundation, Jeff Bezos, Larry Ellison, Larry Page, Mayo Clinic, metformin, PespsiCo, Peter Thiel, TAME, Targeting Aging with Metformin
Recent Comments