Category: New Compounds and Treatments

Categories : New Compounds and TreatmentsTags : 1 Comment

Surprising Drug Duo Outperforms Oseltamivir in Treating Flu

On By ModernMedia
Photo by Andrea Piacquadio on Pexels

In a potential game-changer for how we treat the flu, scientists at the Hebrew University of Jerusalem have unveiled a new drug pairing that outperforms oseltamivir – the most widely used anti-influenza medication – against even the deadliest flu strains, including bird(avian) and swine flu.

The surprising duo? One of them is theobromine, a compound found in chocolate.

In a study recently published in PNAS, researchers, led by Prof Isaiah (Shy) Arkin, have developed a novel combination therapy that targets a key weakness in the influenza virus: its ion channel, a microscopic gate the virus uses to replicate and spread. By blocking this gate, the team effectively cut off the virus’s ability to survive.

Their study, conducted at Israel’s new Barry Skolnick Biosafety Level 3 facility, tested this combo, consisting of theobromine and a lesser-known compound called arainosine, against a broad range of flu viruses. In both cell cultures and animal trials, the treatment dramatically outperformed oseltamivir (Tamiflu), especially against drug-resistant strains.

“We’re not just offering a better flu drug,” said Prof Arkin. “We’re introducing a new way to target viruses – one that may help us prepare for future pandemics.”

Why It Matters

The stakes are high: Influenza continues to sweep the globe each year, with unpredictable mutations that challenge vaccines and existing drugs. In the U.S. alone, seasonal flu costs an estimated $87 billion annually in healthcare and lost productivity. Past pandemics – like the 2009 swine flu – have inflicted even deeper global costs, and the cost of future pandemics was estimated to rise even further up to $4.4 trillion.

Meanwhile, outbreaks of avian flu have devastated poultry industries and sparked fears of cross-species transmission to humans. Just one recent outbreak in the U.S. led to the loss of 40 million birds and billions in economic damage.

Current flu treatments, like oseltamivir, are losing ground as the virus adapts. Most drugs in use target a viral protein that mutates frequently, rendering treatments less effective over time. That’s where Arkin’s team saw an opening.

A New Strategy for Old Viruses

Instead of fighting the virus head-on with traditional antivirals, the researchers zeroed in on the M2 ion channel – a crucial viral feature that helps the virus replicate. Past efforts to block this channel have largely failed due to drug resistance. But the new theobromine–arainosine combo sidesteps this resistance, even neutralising hard-to-treat strains.

The team discovered the combo by scanning a library of repurposed compounds, many originally developed for other diseases, and testing their effects on both drug-sensitive and drug-resistant versions of the virus.

Broader Implications

The implications extend beyond influenza. Because many viruses, including coronaviruses, also rely on ion channels, this new approach could form the basis of future antiviral strategies.

The next steps include human clinical trials, but the early results offer hope not just for a better flu treatment, but for a smarter way to fight viral disease in general. ViroBlock, a startup company emanating from the Hebrew University, has been entrusted to develop the discoveries to reach the public.

Source: Hebrew University of Jerusalem

Categories : New Compounds and TreatmentsTags :

Small Molecule Could Alleviate Paracetamol-induced Liver Injury

On By ModernMedia
Human liver. Credit: NIH

Paracetamol (acetaminophen) is one of the most common painkillers and is found in hundreds of different medications. While safe at recommended doses, paracetamol overdose is the leading cause of acute liver injury in the U.S. Now, researchers propose that a new molecule has the potential to treat acetaminophen-induced liver injury (AILI) and other inflammatory conditions. They conducted a small-scale mouse trial and found that the new compound decreased AILI-caused liver inflammation and prevented liver damage. 

Jannatun Nayem Namme, a graduate student at Virginia Commonwealth University, will present her team’s results at the fall meeting of the American Chemical Society (ACS). ACS Fall 2025 is being held Aug. 17-21; it features about 9000 presentations on a range of science topics.  

Most acetaminophen overdoses are accidental, often due to people unintentionally consuming multiple products containing the painkiller or misinterpreting dosage. After taking a recommended amount of paracetamol, a person’s liver converts a small percentage of it into a toxic molecule called N-acetyl-p-benzoquinone imine (NAPQI). Normally, the liver can quickly metabolise NAPQI into a non-toxic form. But if a person takes too much acetaminophen, NAPQI builds up and causes irreversible cell damage, leading to liver injury or death. Currently, N-acetylcysteine is the only drug available to treat AILI, and it must be administered within eight hours of overdose. 

To develop novel treatments for inflammatory conditions, such as AILI, and neurodegenerative conditions, Namme and her colleagues previously focused on small molecules that reduce the activity of inflammation-causing proteins, known as inflammasomes. Inflammasomes are also involved in pyroptosis, a type of cellular death associated with AILI. While developing inflammasome inhibitors, the researchers noticed that some of the compounds they created could target a specific inflammatory protein called gasdermin D (GSDMD). GSDMD is involved in pyroptosis. 

Namme and the team synthesised several different GSDMD-inhibiting compounds and tested them for their ability to bind to GSDMD. They discovered that one small molecule, which they labelled YM81, selectively binds to and inhibits GSDMD from initiating pyroptosis.  

Next, the researchers treated five mice with AILI using YM81 and compared them to 10 mice given a placebo. They monitored the extent of liver damage in the animals 17 hours after the acetaminophen overdose. Compared to the placebo group, mice treated with YM81 had significantly lower levels of alanine transaminase and aspartate transaminase, two liver injury biomarkers. These results indicate that the YM81 treatment helped decrease liver inflammation by inhibiting GSDMD. 

Shijun Zhang, the study’s principal investigator, says that YM81 is in the early stages of drug development. “In the future, we will focus on optimising YM81 to increase its potency, safety and stability, in addition to exploring its therapeutic potential in additional animal models,” he says. 

Namme adds that GSDMD inhibitors like YM81 have the potential to treat other inflammatory conditions. “GSDMD is a common protein involved in multiple inflammatory and neurodegenerative diseases, such as arthritis, sepsis and gout,” she says. “Targeting GSDMD could offer a therapeutic strategy to reduce the inflammation and damage from multiple diseases and causes.”

Source: American Chemical Society

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Weekly Gel-based Injection for Parkinson’s Could Be a Game Changer

On By ModernMedia

A new weekly injectable drug could transform the lives of more than eight million people living with Parkinson’s disease, potentially replacing the need for multiple daily tablets.

UniSA PhD candidate Deepa Nakmode and Professor Sanjay Garg in the lab. Credit: UniSA

Scientists from the University of South Australia (UniSA) have developed a long-acting injectable formulation that delivers a steady dose of levodopa and carbidopa – two key medications for Parkinson’s – over an entire week.

Their findings have been reported in the journal Drug Delivery and Translational Research.

The biodegradable formulation is delivered in a subcutaneous or intramuscular injection, where it gradually releases the medication over seven days.

Parkinson’s disease is the second most common neurological disorder, affecting more than 8.5 million people worldwide. Currently there is no cure and the symptoms – tremors, rigidity and slow movement – are managed with oral medications that must be taken several times a day.

The frequent dosing is a burden, especially for elderly patients or those with swallowing difficulties, leading to inconsistent medication levels, more side effects, and reduced effectiveness.

Lead researcher Professor Sanjay Garg, from UniSA’s Centre for Pharmaceutical Innovation, says the newly developed injectable could significantly improve treatment outcomes and patient adherence.

“Our goal was to create a formulation that simplifies treatment, improves patient compliance, and maintains consistent therapeutic levels of medication. This weekly injection could be a game-changer for Parkinson’s care,” Prof Garg says.

“Levodopa is the gold-standard therapy for Parkinson’s, but its short life span means it must be taken several times a day.”

UniSA PhD student Deepa Nakmode says the in-situ implant is designed to release both levodopa and carbidopa steadily over one week, maintaining consistent plasma levels and reducing the risks associated with fluctuating drug concentrations.

“After years of focused research, it’s incredibly rewarding to see our innovation in long-acting injectables for Parkinson’s disease reach this stage. Our invention has now been filed for an Australian patent,” Nakmode says.

The injectable gel combines an FDA-approved biodegradable polymer PLGA with Eudragit L-100, a pH-sensitive polymer, to achieve a controlled and sustained drug release.

Extensive lab tests confirmed the system’s effectiveness and safety:

  • More than 90% of the levodopa dose and more than 81% of the carbidopa dose was released over seven days.
  • The implant degraded by over 80% within a week and showed no significant toxicity in cell viability tests.
  • The formulation can be easily administered through a fine 22-gauge needle, minimising discomfort and eliminating the need for surgical implant.

“The implications of this research are profound,” Prof Garg says. “By reducing the frequency of dosing from multiple times a day to a weekly injection is a major step forward in Parkinson’s therapy. We’re not just improving how the drug is delivered; we’re improving patients’ lives.”

Prof Garg says the technology could also be adapted for other chronic conditions such as cancer, diabetes, neurodegenerative disorders, pain management, and chronic infections that require long-term drug delivery.in

The system can be tuned to release drugs over a period ranging from a few days to several weeks depending on therapeutic needs.

UniSA scientists hope to start clinical trials in the near future and are exploring commercialisation opportunities.

Source: University of South Australia

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Royalty-based Method Offers New Model for ALS Drug Development

On By ModernMedia
Photo by Rodion Kutsaiev on Unsplash

A team of researchers from the MIT Sloan School of Management, the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH), Questrom School of Business at Boston University, and QLS Advisors have introduced a new approach to funding clinical trials for amyotrophic lateral sclerosis (ALS) therapies. The study, “Financing Drug Development via Adaptive Platform Trials,” published today in PLOS One, outlines a financing model that merges the efficiencies of adaptive platform trials — lower costs and shorter durations — with an innovative, royalty-based investment structure designed to accelerate therapeutic development for ALS and other serious diseases.

ALS — also often called Lou Gehrig’s disease — is a progressive, neurodegenerative disease with no cure. Despite its devastating impact, the pace of new therapy development has remained sluggish—largely due to the high cost, duration, and risks associated with traditional clinical trials. This bottleneck has often discouraged conventional investors, leaving promising research to languish.

To tackle this challenge, the authors propose an investment fund that finances half the cost of an adaptive platform trial in exchange for future royalties from successful drugs that emerge from the trial. Adaptive platform trials allow multiple drug candidates to be tested simultaneously under a single master protocol, and results are interpreted on a real-time basis to determine efficacy or futility. Drawing on data from the HEALEY ALS Platform Trial administered by the Healey & AMG Center for ALS at MGH, and realistic assumptions, their simulated fund generated an expected return of 28%, with a 22% probability of total loss, which may be attractive to more risk-tolerant and impact-driven investors such as hedge funds, sovereign wealth funds, family offices, and philanthropists. Their findings suggest that generating returns more palatable for mainstream investors could be achieved by funding multiple platform trials simultaneously and by employing financial tools such as securitization — a method that bundles future income from assets like loans or royalties into investment products.

“ALS clinical trials face significant hurdles — from high costs and long timelines to limited funding pools,” said Merit E. Cudkowicz, MD, MSC, Executive Director at Mass General Brigham Neuroscience Institute and Director of the Healey & AMG Center for ALS. “Our platform trial model has already shown that we can test more therapies more efficiently. What’s still missing is sustainable financing. This novel approach could be a game-changer, enabling us to launch trials faster, include more promising therapies, and bring us closer to our shared goal: delivering effective treatments to people with ALS as quickly as possible.”

While their study focused on ALS, the authors believe such a funding model could be applied to other disease areas as well, especially those with well-defined endpoints, where treatment success can be measured clearly and reliably.

Source: Mass General Brigham

Categories : New Compounds and Treatments OphthalmologyTags :

Boosting Apolipoprotein-M May Block Age-related Macular Degeneration

On By ModernMedia
Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

A new study from Washington University School of Medicine in St. Louis identifies a possible way to slow or block progression of age-related macular degeneration, a leading cause of blindness in people over age 50. The WashU Medicine researchers and their international collaborators implicated problems with cholesterol metabolism in this type of vision loss, perhaps helping to explain the links between macular degeneration and cardiovascular disease, which both worsen with age.

The new findings, using human plasma samples and mouse models of macular degeneration, suggest that increasing the amount of a molecule called apolipoprotein M (ApoM) in the blood fixes problems in cholesterol processing that lead to cellular damage in the eyes and other organs. Various methods of dialing up ApoM could serve as new treatment strategies for age-related macular degeneration and perhaps some forms of heart failure triggered by similar dysfunctional cholesterol processing.

The study appears June 24 in the journal Nature Communications.

“Our study points to a possible way to address a major unmet clinical need,” said senior author Rajendra S. Apte, MD, PhD, professor of ophthalmology and visual sciences at WashU Medicine. “Current therapies that reduce the chance of further vision loss are limited to only the most advanced stages of macular degeneration and do not reverse the disease. Our findings suggest that developing treatments that increase ApoM levels could treat or even prevent the disease and therefore preserve people’s vision as they age.”

In macular degeneration, doctors can see cholesterol-rich deposits under the retina during an eye exam, according to Apte. In early stages, vision might still be normal, but the deposits increase inflammation and other damaging processes the lead to the gradual loss of central vision. In the most common type, “dry” macular degeneration, the cells in the central part of the retina can be damaged, causing a type of neurodegeneration called geographic atrophy, which is similar to what happens in the brain in conditions such as Alzheimer’s disease. Dry macular degeneration can turn into “wet” macular degeneration, in which abnormal blood vessel growth damages vision.

Geographic atrophy and wet macular degeneration are advanced forms of the disease that are accompanied by vision loss. Although some approved therapies for advanced disease are available, the disease process itself is not reversible at that stage.

A common culprit in eye disease and heart failure

In recent years, evidence has emerged that ApoM can serve as a protective molecule with known anti-inflammatory effects and roles in maintaining healthy cholesterol metabolism. With that in mind, Apte and co-senior author Ali Javaheri, MD, PhD, an assistant professor of medicine, were interested in assessing whether reduced ApoM levels, which fall with age, could be involved in the dysfunctional cholesterol metabolism that is at the root of multiple diseases of aging, including macular degeneration and heart disease. They showed that patients with macular degeneration have reduced levels of ApoM circulating in the blood compared with healthy controls. And past work by Javaheri, a WashU Medicine cardiologist, showed that patients with various forms of heart failure also had reduced levels of ApoM in the blood.

This study revealed that ApoM is a key component in the “good cholesterol” pathways that mop up excess “bad” LDL cholesterol and excrete it via the liver.

Apte and Javaheri’s research suggests that when ApoM is low, cells in the retina and heart muscle can’t correctly metabolise cholesterol deposits and struggle to clear these accumulating lipids. When these lipids build up, it leads to inflammation and cellular damage.

To see if they could reverse the harmful effects of low ApoM, the researchers increased ApoM levels in mouse models of macular degeneration, using genetic modification or plasma transfer from other mice. The mice showed evidence of improved retinal health, improved function of light-sensing cells in the retina and reduced accumulation of cholesterol deposits. The researchers further found evidence that ApoM triggers a signalling pathway that breaks down the cholesterol in cellular compartments called lysosomes, which are known for playing important roles in disposing of cellular waste.

The researchers also found that ApoM must be bound to a molecule called sphingosine-1-phosphate (S1P) to get the beneficial effects of ApoM treatment in the mice.

The findings also could have implications for future interventions that raise ApoM in patients with heart failure.

“One of the exciting things about this collaboration is realising the links between retinal pigment epithelial cells and heart muscle cell, which are both vulnerable to low ApoM,” Javeheri said. “It is possible that the interaction between ApoM and S1P is regulating cholesterol metabolism in both cell types. We look forward to exploring strategies to increase ApoM in ways that could help the eye and the heart maintain healthy cholesterol metabolism over time and stave off two major diseases of aging.”

Source: WashU Medicine

Categories : Cancer New Compounds and TreatmentsTags :

Aspergillus Flavus: From the ‘Curse of Tutankhamun’ to New Cancer Treatment

On By ModernMedia
A sample of Aspergillus flavus cultured in the Gao Lab. (Credit: Bella Ciervo)

University of Pennsylvania-led researchers have turned a deadly fungus into a potent cancer-fighting compound. After isolating a new class of molecules from Aspergillus flavus, a toxic crop fungus linked to deaths in excavating ancient tombs, the researchers modified the chemicals and tested them against leukaemia cells. The result was a promising cancer-killing compound that rivals FDA-approved drugs and opens up new frontiers in the discovery of more fungal medicines.

“Fungi gave us penicillin,” says Sherry Gao, Presidential Penn Compact Associate Professor in Chemical and Biomolecular Engineering (CBE) and in Bioengineering (BE) and senior author of a new paper in Nature Chemical Biology on the findings. “These results show that many more medicines derived from natural products remain to be found.”

From Curse to Cure

A. flavus, named for its yellow spores, has long been a microbial villain. After archaeologists opened King Tutankhamun’s tomb in the 1920s, a series of untimely deaths among the excavation team fuelled rumours of a pharaoh’s curse. Decades later, doctors theorised that fungal spores, dormant for millennia, could have played a role.

In the 1970s, a dozen scientists entered the tomb of Casimir IV in Poland. Within weeks, 10 of them died. Later investigations revealed the tomb contained A. flavus, whose toxins can lead to lung infections, especially in people with compromised immune systems.

Now, that same fungus is the unlikely source of a promising new cancer therapy.

A Rare Fungal Find

The therapy in question is a class of ribosomally synthesised and post-translationally modified peptides, or RiPPs, pronounced like the “rip” in a piece of fabric. The name refers to how the compound is produced – by the ribosome, a tiny cellular structure that makes proteins – and the fact that it is modified later, in this case, to enhance its cancer-killing properties.

“Purifying these chemicals is difficult,” says Qiuyue Nie, a postdoctoral fellow in CBE and the paper’s first author. While thousands of RiPPs have been identified in bacteria, only a handful have been found in fungi. In part, this is because past researchers misidentified fungal RiPPs as non-ribosomal peptides and had little understanding of how fungi created the molecules. “The synthesis of these compounds is complicated,” adds Nie. “But that’s also what gives them this remarkable bioactivity.”

Hunting for Chemicals

To find more fungal RiPPs, the researchers first scanned a dozen strains of Aspergillus, which previous research suggested might contain more of the chemicals.

By comparing chemicals produced by these strains with known RiPP building blocks, the researchers identified A. flavus as a promising candidate for further study.

Genetic analysis pointed to a particular protein in A. flavus as a source of fungal RiPPs. When the researchers turned the genes that create that protein off, the chemical markers indicating the presence of RiPPs also disappeared.

This novel approach – combining metabolic and genetic information – not only pinpointed the source of fungal RiPPs in A. flavus, but could be used to find more fungal RiPPs in the future.

A Potent New Medicine

After purifying four different RiPPs, the researchers found the molecules shared a unique structure of interlocking rings. The researchers named these molecules, which have never been previously described, after the fungus in which they were found: asperigimycins.

Even with no modification, when mixed with human cancer cells, asperigimycins demonstrated medical potential: two of the four variants had potent effects against leukaemia cells.

Another variant, to which the researchers added a lipid found in bees’ royal jelly, performed as well as cytarabine and daunorubicin, two FDA-approved drugs that have been used for decades to treat leukaemia.

Cracking the Code of Cell Entry

To understand why lipids enhanced asperigimycins’ potency, the researchers selectively turned genes on and off in the leukaemia cells. One gene, SLC46A3, proved critical in allowing asperigimycins to enter leukaemia cells in sufficient numbers.

That gene helps materials exit lysosomes, the tiny sacs that collect foreign materials entering human cells. “This gene acts like a gateway,” says Nie. “It doesn’t just help asperigimycins get into cells, it may also enable other ‘cyclic peptides’ to do the same.”

Like asperigimycins, those chemicals have medicinal properties – nearly two dozen cyclic peptides have received clinical approval since 2000 to treat diseases as varied as cancer and lupus – but many of them need modification to enter cells in sufficient quantities.

“Knowing that lipids can affect how this gene transports chemicals into cells gives us another tool for drug development,” says Nie.

Disrupting Cell Division

Through further experimentation, the researchers found that asperigimycins likely disrupt the process of cell division. “Cancer cells divide uncontrollably,” says Gao. “These compounds block the formation of microtubules, which are essential for cell division.”

Notably, the compounds had little to no effect on breast, liver or lung cancer cells – or a range of bacteria and fungi – suggesting that asperigimycins’ disruptive effects are specific to certain types of cells, a critical feature for any future medication.

Future Directions

In addition to demonstrating the medical potential of asperigimycins, the researchers identified similar clusters of genes in other fungi, suggesting that more fungal RiPPS remain to be discovered. “Even though only a few have been found, almost all of them have strong bioactivity,” says Nie. “This is an unexplored region with tremendous potential.”

The next step is to test asperigimycins in animal models, with the hope of one day moving to human clinical trials. “Nature has given us this incredible pharmacy,” says Gao. “It’s up to us to uncover its secrets. As engineers, we’re excited to keep exploring, learning from nature and using that knowledge to design better solutions.”

Source: University of Pennsylvania School of Engineering and Applied Science

Categories : Metabolic Disorders New Compounds and TreatmentsTags :

New Weight Loss Drug Targets Four Hormone Receptors

On By ModernMedia
Photo by I Yunmai on Unsplash

In the US, drugs like semaglutide are used by over 15 million adults in the U.S., or 4.5% of the population for diabetes and also weight loss. Despite their effectiveness, they have drawbacks. Their effect may not last after discontinuing use, and side effects including osteoporosis and muscle loss have raised concerns about long-term harms. They also induce nausea, which can make it difficult to stay the course of treatment.

Now Tufts researchers led by Professor Krishna Kumar, have designed a new, next-generation compound with hopes that it could be more effective with fewer side effects, which they report in a paper in the Journal of the American Chemical Society. 

While weight loss drugs currently on the market and in development target one, two, or even three hormone receptors related to glucose metabolism and the desire to eat, the Tufts team has identified a fourth target that could potentially further enhance the control strategy.

“Obesity is linked to over 180 different disease conditions, including cancer, cardiovascular disease, osteoarthritis, liver disease, and type 2 diabetes, and affects over 650 million people worldwide,” said Kumar. “What drives us is the idea that we can design a single drug to treat obesity and simultaneously mitigate the risk of developing a long list of health problems plaguing society.”

How the Drugs Work

After a meal, the hormone glucagon-like peptide 1 (GLP-1) is released to help stimulate the production of insulin and the uptake of glucose in muscle and other tissues. With the cells now loaded with fuel, the level of glucose in the blood returns to normal. Semaglutide uses GLP-1 with slight modifications to increase its availability in the bloodstream. Its success in controlling blood glucose has prompted the American Diabetes Association to recommend it and other GLP-1-based drugs as the new first line injectable treatments for diabetes, ahead of insulin.

But GLP-1 also acts directly on the brain, prompting satiety after a meal, and it slows down the rate at which stomach contents are emptied into the intestines, evening out the release of nutrients and glucose into the bloodstream. That’s why it has also become extremely popular as a weight loss treatment.

It’s still not a perfect drug strategy for weight loss, though. “The biggest problem with GLP-1 drugs is that they have to be injected once a week, and they can induce a very strong feeling of nausea,” said Kumar. “As much as 40% of people using these drugs give up after the first month.”

A second hormone released after eating is glucose-dependent insulinotropic peptide (GIP). It also makes us feel full after a meal. GIP looks a lot like GLP-1, so rather than administer two drugs, researchers created one peptide that incorporates structural elements of both – what’s called in drug development a chimera. That drug, tirzepatide, has the added benefit of significantly reducing nausea. As a more tolerable treatment, it may overtake semaglutide in the weight loss market. 

“And then there is a third hormone, glucagon,” said Kumar. “Paradoxically, it actually increases blood glucose, but at the same time increases the expenditure of energy in cells of the body, raises body temperature, and suppresses appetite.” By adding glucagon to the mix, GLP-1 and GIP end up neutralizing its glucose-enhancing effect, leaving the remaining functionalities of all three hormones working together to enhance weight loss.

Glucagon is also similar in structure to GLP-1 and GIP, so drug developers created a single chimera peptide that incorporates elements of all three hormones, which can be recognised by their three separate receptors. That drug, called retatrudide, is currently in clinical trials that indicate even greater achievable weight loss (up to 24%) compared to the original GLP-1 drugs (6-15%).

Going for the Weight Loss Gold Standard with a Fourth Target

“The goal that people are trying to shoot for is bariatric surgery,” said Kumar. That’s a surgical procedure significantly reducing the size of the stomach, which can achieve long-lasting weight loss up to 30%. “For individuals with persistent obesity and potential deadly associated conditions, it becomes a necessary but invasive treatment.” 

Current injectable weight loss drugs still fall short of that gold standard, so the Tufts chemists are focused on a drug redesign that could match the 30% weight loss outcome. 

“There is one more hormone we wanted to bring in to complete a weight control quartet,” said Tristan Dinsmore, a graduate student in the Kumar lab and the lead author of the study. “It’s called peptide YY (PYY). This molecule is also secreted by the gut after we eat a meal, and its job is to reduce appetite and slow the process of emptying food from the stomach, but via different mechanisms than either GLP-1 or GIP. It may also be involved in directly ‘burning off’ fat.”

PYY is from a separate and structurally unrelated class of hormones than the first three, so blending its structure into a chimeric peptide that also mimics GLP-1, GIP, and glucagon was not easy. Instead, the Tufts team was able to join two peptide segments end-to-end, creating a new ‘tetra-functional’ clinical candidate.

“One of the limitations of the current drugs is that individual variation, possibly including how people express target receptors or respond to their corresponding hormones, can lead to lesser than desired weight loss outcomes in many patients,” said Martin Beinborn, visiting scholar in the Department of Chemistry. “By hitting four different hormone receptors at the same time, we hope to improve the chances of averaging out such variation toward the goal of achieving greater and more consistent overall effectiveness.”

“A second issue is that patients tend to regain weight after discontinuing currently available GLP-1 related drugs,” said Beinborn, who notes that lifestyle changes should ideally be a complement to medication treatment. This two-pronged approach will not only support reaching and keeping one’s target weight, but may also help preserve bone and muscle mass.

“Recent studies indicate that weight rebound after drug discontinuation is delayed with the newer, more effective GLP-1 mimetics,” he said. “Extending from this observation, one may speculate that multi-chimeras along the lines of the one we discovered could get us closer to the bariatric surgery standard of lasting weight loss.”

Source: Tufts University

Categories : New Compounds and Treatments Pain ManagementTags :

Experimental Analgesic Could Match Opioids Efficacy – Without the High 

On By ModernMedia
Photo by Louis Reed on Unsplash

An experimental drug developed at Duke University School of Medicine could offer powerful pain relief without the dangerous side effects of opioids.

Called SBI-810, the drug is part of a new generation of compounds designed to target a receptor on the nerves and spinal cord. While opioids flood multiple cellular pathways indiscriminately, SBI-810 takes a more focused approach, activating only a specific pain-relief pathway that avoids the euphoric “high” linked to addiction.

In tests in mice, SBI-810 worked well on its own and, when used in combination, made opioids more effective at lower doses, according to the study published in Cell.

“What makes this compound exciting is that it is both analgesic and non-opioid,” said senior study author Ru-Rong Ji, PhD, an anaesthesiology and neurobiology researcher who directs the Duke Anesthesiology Center for Translational Pain Medicine.

Even more encouraging: it prevented common side effects like constipation and buildup of tolerance, which often forces patients to need stronger and more frequent doses of opioids over time.

SBI-810 is in early development, but Duke researchers are aiming for human trials soon and have secured multiple patents for the discovery.

There’s an urgent need for non-opioid pain relievers. Researchers said the drug could be a safer option for treating both short-term and chronic pain for those recovering from surgery or living with diabetic nerve pain.

SBI-810 is designed to target the brain receptor neurotensin receptor 1. Using a method known as biased agonism, it switches on a specific signal – β-arrestin-2 – linked to pain relief, while avoiding other signals that can cause side effects or addiction.

“The receptor is expressed on sensory neurons and the brain and spinal cord,” Ji said. “It’s a promising target for treating acute and chronic pain.”

SBI-810 effectively relieved pain from surgical incisions, bone fractures, and nerve injuries better than some existing painkillers. When injected in mice, it reduced signs of spontaneous discomfort, such as guarding and facial grimacing.

Duke scientists compared SBI-810 to oliceridine, a newer type of opioid used in hospitals, and found SBI-810 worked better in some situations, with fewer signs of distress.

Unlike opioids like morphine, SBI-810 didn’t cause tolerance after repeated use. It also outperformed gabapentin, a common drug for nerve pain, and didn’t cause sedation or memory problems, which are often seen with gabapentin.

Researchers said the compound’s dual action – on both the peripheral and central nervous systems– could offer a new kind of balance in pain medicine: powerful enough to work, yet specific enough to avoid harm.

Source: Duke University

Categories : Cancer New Compounds and TreatmentsTags :

Scientific Breakthrough: Price of Costly Cancer Drug can be Halved

On By ModernMedia
Source: Unsplash CC0

Taxol is one of the most commonly prescribed chemotherapy drugs for breast, ovarian, cervical, and lung cancer. Yet producing the drug is complex, costly, and environmentally burdensome, as it currently relies on a complicated chemical semi-synthesis. For 30 years, scientists around the world have tried to understand how taxol, a natural compound derived from the Pacific yew tree, forms in nature. Decoding this process would allow for biotech-based production. But the final steps remained unknown – until now.

A research team from the University of Copenhagen has succeeded in finding the two missing pieces: They have identified the enzymes responsible for the two critical final steps in the biosynthetic pathway that makes Taxol active as a drug.

“Taxol has been the Holy Grail in this research field for decades because it’s an exceptionally complex molecule. But with the discovery of the final two enzymes, we now fully understand how it’s formed. This has allowed us to develop a biotechnological method to produce taxol in yeast cells,” says Sotirios Kampranis, Professor at the Department of Plant and Environmental Sciences and senior author of the study published in Nature Synthesis.

The method involves cloning the taxol-producing genes from the yew tree and inserting them into yeast cells. These engineered yeast cells then become host organisms or micro-factories with the full recipe to produce taxol.

Affecting women in developing countries

The research team from the University of Copenhagen has applied for patenting the method and is in the process of launching a spin-out company to manufacture biosynthetic Taxol. 

“Using this method, we can produce Taxol cheaper than current conventional methods. Looking ahead, once we refine the process further, we expect to be able to reduce the cost by half,” says Assistant Professor and first author Feiyan Liang.

Lower prices are especially crucial as ovarian cancer is on the rise globally. The prevalence of the disease is expected to increase by over 55% by 2050, with the vast majority of cases in low and middle-income countries. The number of women dying from ovarian cancer is projected to rise by nearly 70% in the same period.

Currently, taxol costs more than USD20 000 per kilogram, making it one of the most expensive active pharmaceutical ingredients in use.

“We see increasing demand for Taxol in many developing countries, where the high price is a major barrier. We hope our work will contribute to lower-priced drugs so that more people can have access to cancer treatment,” Feiyan Liang says.

Much more sustainable

The new method is not only more cost-effective but also more sustainable than chemical synthesis. One advantage is that the procedure does not involve harmful chemicals and solvents common in chemical production. Another advantage is that it allows the use of more crude, less purified extracts from yew needles as starting material – much cheaper than the ultra-pure inputs required in chemical semi-synthesis. On top of that, the materials can be recycled.

“We want to show that it’s possible to build a biotechnological drug production that is both sustainable and low-cost. There are very few examples of that today, but we now have the foundation to make it happen,” says Sotirios Kampranis. 

TWO TREES PER TREATMENT

  • Taxol was originally extracted from the inside bark of the Pacific yew tree (Taxus brevifolia), but as the taxol content in the bark is very low, harvesting it meant removing all the bark and as a result of this killing the tree.
  • Yew trees take 70 to 100 years to mature. Producing just one treatment required about two trees, making this method highly unsustainable. It was abandoned years ago, though wild yew trees are still under pressure in some regions.
  • Today’s most common method involves harvesting a similar compound from yew needles for chemical synthesis, but the cost of this process is still high, which is why the average price of taxol exceeds USD 20 000 per kilogram (source: pharmacompass.com).

Source: University of Copenhagen – Faculty of Science

Categories : Cancer New Compounds and TreatmentsTags :

Hyperbaric Oxygen for Radiation-induced Injuries Provides Lasting Relief

On By ModernMedia
Photo by National Cancer Institute on Unsplash

Hyperbaric oxygen treatment provides long-term relief for patients suffering from late radiation-induced injuries after treatment of cancer in the lower abdominal area. Five years after hyperbaric oxygen therapy, the positive effects remain. This has been shown in a study conducted at the University of Gothenburg, published in eClinicalMedicine.

Radiation therapy is a component of many cancer treatments in organs such as the prostate, colon, ovaries and cervix. While tumour cells are destroyed, 5-10% of patients experience severe side effects due to healthy tissue being affected by the radiation therapy.

Symptoms may include urinary incontinence, bleeding and severe pain from the lower abdomen that becomes both physically and socially disabling. These problems can occur several years after radiation therapy and cause chronic and increasing discomfort.

Researchers have previously shown that patients experience significantly less discomfort after hyperbaric oxygen treatment. The question in the current study was whether the relief would last over several years. The time aspect is important for future decisions on broader use of the method.

From severe problems to a normal life 

Initially, all participants had severe symptoms. The group that was randomly assigned to hyperbaric oxygen treatment fared significantly better than the control group in terms of incontinence, bleeding and pain. The positive effects were sustained over the five year follow-up period. 

Nicklas Oscarsson, senior consultant in anaesthesiology and intensive care, and researcher at the University of Gothenburg and Sahlgrenska University Hospital was the principle investigator of the study:

“Patients who respond to treatment go from being very distressed by their symptoms and restricted by their need to have quick access to a toilet, to being able to live a fully normal life. Now we know that this pronounced improvement last for at least five years. The treatment can therefore lead to the healing of an otherwise chronic injury,” he states.

The effects achieved are due to cells sensing and adapting to high oxygen levels. The increased levels of oxygen provided in a hyperbaric chamber increases vascular growth and stops chronic inflammation, reducing severe side effects.

For the oxygen treatments, participants spent 90 minutes a day in a hyperbaric chamber on 30-40 occasions, at a pressure of 1.4 atmospheres (equivalent to 14m underwater). The control group received the usual treatment, which normally includes medication and physiotherapy, for example.

The capacity already exists today

“We have reason to believe that there are many patients with severe symptoms who are never referred to hyperbaric oxygen therapy. Today we already have the capacity to treat more patients, but we need to be better at sharing our knowledge with our colleagues and with patient associations,” says Nicklas Oscarsson.

Severe side effects after radiation therapy are one of the main limitations on the dose of radiation that can be given in cancer treatment. The availability of a treatment that can reduce the number of people affected by these side effects opens the door to increased radiation doses and thus more curable tumours. One area for further investigation, according to the researchers, is whether early treatment with hyperbaric oxygen can prevent the occurrence of severe side effects.

The results are based on surveys and analyses of the participants who have been involved all the way, 70 adults. The treatments were conducted at five university hospitals in the Nordic countries: Rigshospitalet in Denmark, Turku in Finland, Haukeland in Norway, and Karolinska and Sahlgrenska in Sweden.

Source: University of Gothenburg