Gel-like Implant Destroys Pancreatic Cancer

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.

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Self-assembling Molecules Asphyxiate Cancerous Cells

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,  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  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 . “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  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/

Sound Plus Electrical Stimulation to Treat Chronic Pain

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 “tactilecortex, 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/

New Drug Treats Cataracts Without the Need for Surgery

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 oneA 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 cholesterolThis 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 proteinsIn 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/

Artificial Intelligence Finds New Drug Molecules a Thousand Times Faster

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 “fitbetween 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/

‘Masked’ Cancer Drug Sneaks Through Body

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/

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/

Drug Prevents Breast Cancer Recurrence and Metastasis

Even when detected early, some cancers are more aggressive and more fatal than others. This is the case, for example, with triple negative breast cancer which accounts for 10 to 15% of all breast cancers. This cancer affects 1,000 patients per year in Belgium, while the figure worldwide is 225,000. Around half of the patients will develop local recurrences and metastases, regardless of the treatment they receive. No specific treatment is currently capable of preventing these two events. Patients suffering from pervasive triple negative breast cancer have only a one-in-ten chance of a cure. In 2014, Pierre Sonveaux, a researcher at the University of Louvain (UCLouvain) Institute for experimental and clinical research, succeeded in demonstrating the principle that it was possible to prevent the appearance of melanoma tumour metastases in mice. However, the experimental molecules used at the time were far from being drugs.

Since then, the UCLouvain researcher and his team, including post-doctoral researcher Tania Capeloa, have continued their work thanks in particular to sponsorship obtained by the UCLouvain Foundation. They have now succeeded in establishing that a drug developed for diseases other than cancer, MitoQ, avoids the appearance of metastases in 80% and local recurrences of human breast cancer in 75% of cases in mice. Conversely, most of the mice not treated suffered a recurrence of their cancer, which spread.

To do this, the researchers treated mice affected by human breast cancer. They treated them as hospital patients are treated, i.e. by combining surgery with a carefully dosed cocktail of standard chemotherapies. However, the UCLouvain researchers supplemented this standard treatment with the new molecule, MitoQ. They not only demonstrated that the administration of MitoQ is compatible with standard chemotherapies, but also that this innovative treatment prevents both relapses and metastases of breast cancer in mice. “We expected to be able to block the metastases, says Pierre Sonveaux enthusiastically. But preventing the recurrence of the cancer was totally unexpected. Getting this type of result is a huge motivation for us to carry on.” In short, this is a giant step given that the three main causes of cancer mortality are recurrences, the spread of the cancer caused by metastasis and resistance to treatment. And that there is currently no other known molecule capable of acting like MitoQ.

How does it work? Cancers consist of two types of cancerous cells: those that proliferate and are sensitive to clinical treatments and those that are dormant and that bide their time. Such cells are more harmful. The problem? These cancerous stem cells are resistant to clinical treatments. They result in metastases and if, unfortunately, cancer surgery fails to remove them all, they cause recurrences. These relapses are currently treated using chemotherapy. However, this tends to be relatively ineffective owing to the resistance to treatment developed by the tumorous cells . This is where the important discovery of the UCLouvain scientists comes in: the molecule MitoQ stops cancerous stem cells from awakening.

What next? MitoQ has already come through the first clinical phase successfully. It has been tested on healthy patients, both men and women, and proves to be only slightly toxic (nausea, vomiting). In addition, its behaviour is known. What next? The discovery made by the UCLouvain scientists opens wide the path for the clinical 2 phase, intended to demonstrate the efficacy of the new treatment in cancer patients.

Source: https://uclouvain.be/
AND
https://www.thebrighterside.news

Smart Contact Lens to Treat Glaucoma

A flexible contact lens that senses eye pressure and releases a drug on-demand could help treat glaucoma, the second leading global cause of blindness worldwide. The compact wireless device, which has been developed by a team of Chinese researchers and tested in pig and rabbit eyes so far, appears to detect and reduce rising eye pressure, one of the usual causes of glaucoma.

Glaucoma is an umbrella term for a group of eye diseases where damage to the optic nerve, which relays visual information to the brain, causes irreversible vision loss and blindness in millions of people worldwide. Where this new research makes ground is in developing a device capable of detecting changes in eye pressure and delivering therapeutic drugs as needed. Recent efforts to develop smart contact lenses as wearable devices for treating eye conditions have either focused on sensing pressure changes in the eye or delivering a drug – but not both – and glaucoma treatment usually involves eye drops, laser therapy, or surgery to reduce eye pressure. While it sounds exciting, keep in mind that as scientists continue experimenting with all sorts of nifty devices for treating eye diseases, early detection of glaucoma and timely treatment remains vital.

Once detected, therapy for glaucoma can arrest or slow its deterioration in the majority of cases,” Jaimie Steinmetz, a research scientist at the Washington-based Institute for Health Metrics and Evaluation, and collaborators wrote in 2020 when analyzing the global burden of eye diseases, including glaucoma. But glaucoma is typically hard to catch because peripheral vision is the first to go, and devices used to diagnose the condition only provide snapshot measurements of intraocular pressure, which fluctuates with activity and sleep-wake cycles.

Hence the importance of improving systems of surveillance, highlighting risk among family members of cases, and effectiveness of care once treatment is initiated,” Steinmetz and co-authors stressThat said, contact lenses which sit snug against the eye hold great appeal for delivering therapies for eye conditions. But incorporating electrical circuits and sensors into small, flexible, curved, and ultra-thin contact lenses presents a serious engineering challenge. For something like this to work, it needs to be sensitive enough to detect pressure changes and release precise amounts of drug on demand – all without blocking vision and irritating the eye. “It is highly challenging to install an intricate theranostic system composited by multi-modules on a contact lens,” electrical engineer Cheng Yang of Sun Yat-Sen University and colleagues write in their paper.

AI-designed Antibody Enters Clinical Trials

The Israeli company Biolojic Design will conduct a trial for cancer patients in Australia with a new type of drugAulos Biosciences is now recruiting cancer patients to try it’s world’s first antibody drug designed by a computer. The computationally designed antibody, known as AU-007, was planned by the artificial intelligence platform of Israeli biotech company Biolojic Design from Rehovot, in a way that would target a protein in the human body known as interleukin-2 (IL-2). The goal is for the IL-2 pathway to activate the body’s immune system and attack the tumors.

The clinical trial will be conducted on patients with final stage solid tumors and will last about a year – but the company hopes to present interim results during 2022. The trial has raised great hopes because if it is successful, it will pave the way for the development of a new type of drug using computational biology and “big data.” Aulos presented pre-clinical data from a study on 19 mice – and they all responded positively to the treatment. In the 17-day trial period of the study, the antibody led to the complete elimination of the tumors in 10 of the mice – and to a significant delay in the development of the tumors in the other nine mice.

Aulos was founded in Boston as a spin-off of Biolojic and venture capital firm Apple Tree Partners, which invested $40 million in the company to advance the antibody project and prove its clinical feasibility. Drugs based on antibodies are considered to be one of the greatest hopes for anti-cancer solutions. Among the best-known in the field are Keytruda, mostly used to treat melanomas and lung cancer; and Herceptin for breast cancer. But the antibodies given today to cancer patients are created by a method that also has disadvantages – most are produced by the immune system in mice, and then are replicated to enable mass production.

Source: https://www.haaretz.com/