JSK Medical Consult

Scientists are using machine learning to find new treatments among thousands of old medicines. By Kate Morgan: March 20, 2025 A little over a year ago, Joseph Coates was told there was only one thing left to decide. Did he want to die at home, or in the hospital? Coates, then 37 and living in Renton, Wash., was barely conscious. For months, he had been battling a rare blood disorder called POEMS syndrome, which had left him with numb hands and feet, an enlarged heart and failing kidneys. Every few days, doctors needed to drain liters of fluid from his abdomen. He became too sick to receive a stem cell transplant — one of the only treatments that could have put him into remission. “I gave up,” he said. “I just thought the end was inevitable.” But Coates’s girlfriend, Tara Theobald, wasn’t ready to quit. So she sent an email begging for help to a doctor in Philadelphia named David Fajgenbaum, whom the couple met a year earlier at a rare disease summit. By the next morning, Dr. Fajgenbaum had replied, suggesting an unconventional combination of chemotherapy, immunotherapy and steroids previously untested as a treatment for Coates’s disorder. Within a week, Coates was responding to treatment. In four months, he was healthy enough for a stem cell transplant. Today, he’s in remission. The lifesaving drug regimen wasn’t thought up by the doctor, or any person. It had been spit out by an artificial intelligence model. In labs around the world, scientists are using A.I. to search among existing medicines for treatments that work for rare diseases. Drug repurposing, as it’s called, is not new, but the use of machine learning is speeding up the process — and could expand the treatment possibilities for people with rare diseases and few options. Thanks to versions of the technology developed by Dr. Fajgenbaum’s team at the University of Pennsylvania and elsewhere, drugs are being quickly repurposed for conditions including rare and aggressive cancers, fatal inflammatory disorders and complex neurological conditions. And often, they’re working. There is a “treasure trove of medicine that could be used for so many other diseases. We just didn’t have a systematic way of looking at it,” said Donald C. Lo, the former head of therapeutic development at the National Center for Advancing Translational Sciences and a scientific lead at Remedi4All, a group focused on drug repurposing. “It’s essentially almost silly not to try this, because these drugs are already approved. You can already buy them at the pharmacy.” The National Institutes of Health defines rare diseases as those which affect fewer than 200,000 people in the United States. But there are thousands of rare diseases, which altogether affect tens of millions of Americans and hundreds of millions of people around the world. And yet, more than 90 percent of rare diseases have no approved treatments, and pharmaceutical giants... https://lnkd.in/dFti6sKa

The oral drug obeldesivir protects nonhuman primates against lethal Ebola virus infection Obeldesivir (ODV; GS-5245) is an orally administered ester prodrug of the parent nucleoside GS-441524 that has broad spectrum antiviral activity inhibiting viral RNA–dependent RNA polymerases. We recently showed that ODV completely protects cynomolgus macaques against lethal infection with Sudan virus when given 24 hours after parenteral exposure. Here, we report that once daily oral ODV treatment of cynomolgus and rhesus macaques for 10 days confers 80 and 100% protection, respectively, against lethal Ebola virus infection when treatment is initiated 24 hours after mucosal (conjunctival) exposure. ODV treatment delayed viral replication to abate excessive inflammation and promote adaptive immunity. For outbreak response, oral antivirals might present substantial advantages over now approved intravenous drugs, such as easy supply, storage, distribution, and administration. Furthermore, these results support the potential of ODV as an oral postexposure prophylaxis with broad spectrum activity across filoviruses. https://lnkd.in/gZw4hVY8

Amplification-free, OR-gated CRISPR-Cascade reaction for pathogen detection in blood samples Significance Rapid pathogen detection is crucial for effective disease management, particularly in bloodstream infections. Current molecular diagnostics often require nucleic acid preamplification, adding time and cost. We introduce an amplification-free CRISPR-Cascade assay that detects pathogenic DNA at attomolar sensitivity within minutes, using a positive feedback loop to enhance signal amplification. Additionally, an OR-gate logic function allows simultaneous detection of multiple pathogens. This approach simplifies and accelerates pathogen detection, offering a versatile and scalable platform for highly sensitive, specific, and multiplexed diagnostics. Our advancements pave the way for next-generation point-of-care tools suitable for diverse clinical and resource-limited settings. Abstract Rapid and accurate detection of DNA from disease-causing pathogens is essential for controlling the spread of infections and administering timely treatments. While traditional molecular diagnostics techniques like PCR are highly sensitive, they include nucleic acid amplification and many need to be performed in centralized laboratories, limiting their utility in point-of-care settings. Recent advances in CRISPR-based diagnostics (CRISPR-Dx) have demonstrated the potential for highly specific molecular detection, but the sensitivity is often constrained by the slow trans-cleavage activity of Cas enzymes, necessitating preamplification of target nucleic acids. In this study, we present a CRISPR-Cascade assay that overcomes these limitations by integrating a positive feedback loop that enables nucleic acid amplification-free detection of pathogenic DNA at atto-molar levels and achieves a signal-to-noise ratio greater than 1.3 within just 10 min. The versatility of the assay is demonstrated through the detection of bloodstream infection pathogens, including Methicillin-Sensitive?Staphylococcus aureus?(MSSA), Methicillin-Resistant?Staphylococcus aureus?(MRSA),?Escherichia coli, and Hepatitis B Virus (HBV) spiked in whole blood samples. Additionally, we introduce a multiplexing OR-function logic gate, further enhancing the potential of the CRISPR-Cascade assay for rapid and accurate diagnostics in clinical settings. Our findings highlight the ability of the CRISPR-Cascade assay to provide highly sensitive and specific molecular detection, paving the way for advanced applications in point-of-care diagnostics and beyond. https://lnkd.in/efgQr5yv

Elevating fungal care: bridging Brazil’s healthcare practices to global standards Brazil faces unique challenges in managing invasive fungal infections (IFIs) due to diverse ecosystems, a rural workforce, and prevalent health conditions. In Europe, IFIs are primarily associated with transplantation, intensive care, and chronic diseases. Inspired by initiatives in the Caribbean and Latin America in 2019, efforts to map global diagnostic and treatment resources expanded to Africa, Europe, and Asia/Pacific. This study conducts a comparative analysis, mainly drawing data from Brazil and Europe, to investigate IFI epidemiology and management. Data were collected through online surveys distributed to Brazilian and European institutions, with collaborations from scientific organizations. Surveys covered institutional profiles, IFI diagnoses, accessibility to diagnostic techniques, and antifungal drugs. A comparative survey involving 96 Brazilian and 388 European institutions revealed variations in the perception and practices related to fungal pathogens. Differences in ranking and prevalence were observed, along with variations in diagnostic procedures, fluorescence dye usage, culture practices, antifungal medication availability, and technological approaches. Europe exhibited higher utilization rates for molecular diagnostic approaches, including PCR tests, and therapeutic drug monitoring (TDM) was more widespread in Europe compared with Brazil, indicating substantial differences in understanding and managing fungal infections. Customized IFI management is crucial, considering regional differences and addressing technological gaps like underutilized PCR. The study advocates for increased international collaboration, targeted training, and enhanced resources to foster a unified global approach in preventing, diagnosing, and treating IFI. https://lnkd.in/ecKeJXgm

The Quest for A.I. ‘Scientific Superintelligence’ Across the spectrum of uses for artificial intelligence, one stands out. The big, inspiring A.I. opportunity on the horizon, experts agree, lies in accelerating and transforming scientific discovery and development. Fed by vast troves of scientific data, A.I. promises to generate new drugs to combat disease, new agriculture to feed the world’s population and new materials to unlock green energy — all in a tiny fraction of the time of traditional research. Technology companies like Microsoft and Google are making A.I. tools for science and collaborating with partners in fields like drug discovery. And the Nobel Prize in Chemistry last year went to scientists using A.I. to predict and create proteins. This month, Lila Sciences went public with its own ambitions to revolutionize science through A.I. The start-up, which is based in Cambridge, Mass., had worked in secret for two years “to build scientific superintelligence to solve humankind’s greatest challenges.” Relying on an experienced team of scientists and $200 million in initial funding, Lila has been developing an A.I. program trained on published and experimental data, as well as the scientific process and reasoning. The start-up then lets that A.I. software run experiments in automated, physical labs with a few scientists to assist. Already, in projects demonstrating the technology, Lila’s A.I. has generated novel antibodies to fight disease and developed new materials for capturing carbon from the atmosphere. Lila turned those experiments into physical results in its lab within months, a process that most likely would take years with conventional research. Experiments like Lila’s have convinced many scientists that A.I. will soon make the hypothesis-experiment-test cycle faster than ever before. In some cases, A.I. could even exceed the human imagination with inventions, turbocharging progress. “A.I. will power the next revolution of this most valuable thing humans ever stumbled across — the scientific method,” said Geoffrey von Maltzahn, Lila’s chief executive, who has a Ph.D. in biomedical engineering and medical physics from the Massachusetts Institute of Technology. The push to reinvent the scientific discovery process builds on the power of generative A.I., which burst into public awareness with the introduction of OpenAI’s ChatGPT just over two years ago. The new technology is trained on data across the internet and can answer questions, write reports and compose email with humanlike fluency. The new breed of A.I. set off a commercial arms race and seemingly limitless spending by tech companies including OpenAI, Microsoft and Google. https://lnkd.in/dspiXkvT

Scientists’ suit against top academic publishers lays bare deep frustration over unpaid peer review Researchers allege journal publishers violated federal antitrust law. In a stark sign of scientists’ escalating frustration with how academic journals operate, researchers are taking on six publishing behemoths in court, arguing that the system is exploitative and overly expensive, and that it relies on illegal and anticompetitive practices. Four researchers have sued six of the world’s biggest publishers: Elsevier, John Wiley & Sons, Sage Publications, Springer Nature, Taylor & Francis, and Wolters Kluwer. The scientists allege that these publishers violated federal antitrust law by colluding not to pay researchers for peer reviewing manuscripts, preventing them from submitting papers to more than one journal at a time, and blocking authors from publicly discussing or sharing work once they’ve submitted it to a journal. “The scheme has been remarkably profitable for the publisher defendants, while doing tremendous damage to science and the public interest,” the plaintiffs claim in the suit filed in the U.S. District Court for the Eastern District of New York.The publishers have said the allegations of collusion are without merit and that they will file a motion to dismiss the case. It’s a case that could have sweeping implications for the research community. Publishing papers is central to how scientists launch and sustain their careers, and researchers have long complained that academia relies on unpaid and underpaid work. But scientific and legal experts told STAT that it’s unusual to see these arguments play out in federal court. They added that while it’s unclear whether this particular lawsuit will succeed, the rising discontent threatens to topple the system tasked with vetting, recording, and communicating biomedical breakthroughs. “The need to confront what has been going on in the scientific publishing area is very overdue,” said Tim Errington, senior director of research at the Center for Open Science. “This [has reached] a fever pitch now.” Academic publishing has changed dramatically since its humble inception in the 17th century, when scientific societies began publishing the work of their members. It’s now standard for new findings to undergo peer review, a process in which outside experts offer critical feedback that a researcher must address before their work ends up in a journal. And papers are now often published by massive, for-profit companies. Many major publishers have profit margins around 40%, exceeding corporate behemoths like Apple and Coca-Cola. https://lnkd.in/eWygRWzG

Novo Nordisk cuts Wegovy prices in half for cash-paying consumers Novo Nordisk now offering weight-loss drug Wegovy for $499 per month Novo Nordisk is cutting the cost of its blockbuster weight-loss drug Wegovy in half for U.S. patients paying cash through its direct-to-patient online pharmacy, as competition in the highly lucrative market stiffens. With NovoCare Pharmacy, uninsured patients or eligible patients with commercial insurance who do not have coverage can access all dose strengths of Wegovy, the brand name for semaglutide, for $499 per month. This includes 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg dose strengths. The list price of the drug before insurance and certain rebates are factored in is well over $1,000. Patients must be prescribed the medication. Those who are eligible can schedule shipments of their Wegovy prescriptions directly to their home through the pharmacy service. These home shipments are fulfilled by CenterWell Pharmacy. NovoCare also offers benefit verification, refill reminders and gives patients access to live support from a NovoCare case manager, according to the pharmaceutical giant. With NovoCare Pharmacy, uninsured patients or eligible patients with commercial insurance who do not have coverage can access all dose strengths of Wegovy for $499 per month. (Carsten Snejbjerg/Bloomberg via / Getty Images) The company said its offering came shortly after the Food and Drug Administration (FDA) confirmed that the shortage of this medication is resolved. All dose strengths of Wegovy meet or exceed both current and projected U.S. demand, according to the pharmaceutical giant. ELI LILLY CUTS PRICES FOR ZEPBOUND WEIGHT-LOSS DRUG AGAIN Just last week, Eli Lilly announced it is expanding the supply and cutting the costs of its weight-loss drug Zepbound, again, effectively broadening access to more patients without insurance with its own self-pay pharmacy. The company, which has also seen a significant boost in profits from Zepbound and Mounjaro — essentially the same drug with different FDA-approved uses — announced that the new vials and pricing are exclusively available through LillyDirect Self Pay Pharmacy Solutions. This isn't the first time Lilly has expanded the supply of its weight-loss drug and cut its cost to effectively compete in the highly lucrative market. The pharmaceutical giant announced in August it was offering 2.5 mg and 5 mg single-dose vials of tirzepatide for the first time in response to growing demand. At the time, Lilly said the doses were also "priced at a 50% or greater discount compared to the list price of all other incretin (GLP-1) medicines for obesity." https://lnkd.in/eMM4BKsb

Survey shows most people unaware of extent of HPV risk in men While most people know women infected with human papillomavirus (HPV) can develop cervical cancer, far fewer are aware the virus poses significant cancer risks to men, as well, and that men are more likely than women to have HPV. And a second study spotlights the rising incidence of cervical cancer rates in rural US counties. The findings on HPV knowledge and misconceptions come from a new survey conducted by The Ohio State University Comprehensive Cancer Center. Researchers said the findings are concerning, especially because rates of throat and tongue cancers in men linked to HPV are rising. 45% of those surveyed did not know of other cancer risks Overall, the survey included 1,005 respondents who completed the survey in early February of this year. Among respondents, 45% did not know if HPV was linked to cancers other than cervical cancer. A similar percentage, 42%, said HPV was more common in women than in men. HPV is actually more common in men, but only women are screened for the virus, the authors said. “This is concerning because more men are infected with HPV than women and they could unknowingly spread it to their partners,” said Electra Paskett, PhD, a professor in The Ohio State University College of Medicine, in a press release from the university’s Wexner Medical Center. Tonsil and tongue-based cancers could become most common Moreover, many of the cancers caused by HPV, including cervical and oropharyngeal (tonsil and tongue base) do not produce symptoms until they are advanced. Ohio State researchers said the rapidly rising rates of HPV-related oropharyngeal (tonsil and tongue base) cancers could be among the most common forms of cancer in adults between the ages of 45 and 65 years old if trends continue. Once exposed, there are currently no treatments for HPV infections, and many who are unvaccinated unknowingly carry and spread high-risk strains of the virus “It can take years or even decades for the genetic changes caused by HPV to take effect and transform into cancer,” said Matthew Old, MD, a head and neck surgeon at Ohio State. “Once exposed, there are currently no treatments for HPV infections, and many who are unvaccinated unknowingly carry and spread high-risk strains of the virus. That’s why vaccination is so important.” Currently, 42 million Americans are estimated to have HPV. https://lnkd.in/gP_ZYS8C

Aging Brains Have a Sugar Problem – And Stanford Scientists May Have Found a Fix By Stanford UniversityMarch 1, 2025 Stanford researchers discovered that age-related thinning of the brain’s glycocalyx—a sugar layer on blood-brain barrier cells—leads to increased permeability, neuroinflammation, and cognitive decline. Restoring key glycans improved barrier integrity and brain function, opening new avenues for treating neurodegenerative diseases. Aging depletes the brain’s protective sugar shield, weakening defenses and fueling cognitive decline, but restoring key sugars may reverse these effects. What if a critical piece of the puzzle of brain aging has been hiding in plain sight? While neuroscience has traditionally focused on proteins and DNA, a team of Stanford researchers dared to shift their focus to sugars—specifically, the complex sugar chains that coat our cells like chain mail. Their investigation uncovered how changes in this sugary armor on the brain’s frontline cells could be crucial to understanding cognitive decline and diseases like Alzheimer’s. “This is like landing on a new planet,” says Nobel laureate Carolyn Bertozzi, professor of chemistry and Baker Family Director of Sarafan ChEM-H, whose groundbreaking research on cell surface sugars and their biological roles laid the groundwork for this interdisciplinary study. “We’re stepping outside for the first time and trying to make sense of what’s out there.” At the center of this discovery is Sophia Shi, a Stanford Bio-X Graduate Fellow, whose doctoral research bridges the labs of Bertozzi and neuroscientist Tony Wyss-Coray, professor of neurology and neurological sciences and the Director of the Phil and Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute. In a study in aging mice, Shi has uncovered striking age-related changes in the sugary coating – called the glycocalyx – on cells that form the blood-brain barrier, a structure that protects the brain by filtering out harmful substances while allowing in essential nutrients. “The glycocalyx is like a forest,” Shi explains. “In young, healthy brains, this forest is lush and thriving. But in older brains, it becomes sparse, patchy, and degraded.” https://lnkd.in/gWs3-GUK

A little-known Chinese company made a drug that beat the world’s biggest-selling medicine By Wayne Chang, Will Ripley and Eric Cheung — China’s DeepSeek shocked the world by delivering unexpected innovation at an unbelievable price. But this disruptive trend isn’t confined to Big Tech: it has been quietly happening in the pharmaceutical sector. In September, Akeso, a little-known Chinese biotech company founded nearly a decade ago shook up the biotech sector with its new lung cancer drug. Ivonescimab, the new drug, was found in a trial conducted in China to have bested Keytruda, the blockbuster medication developed by Merck that has raked in more than $130 billion in sales for the American behemoth that has dominated cancer treatment. Patients treated with Akeso’s new drug went 11.1 months before their tumors began to grow again, compared with 5.8 months for Keytruda, according to clinical data released at the World Conference on Lung Cancer, a top medical forum. Over the course of several days in early September, shares in California-based Summit Therapeutics, Akeso’s US partner, more than doubled to a record high, according to data from Refinitiv. The firm had licensed the right to commercialize the new drug in North America and Europe. At the time, though experts said it was a watershed moment for Chinese pharmaceutical companies, it was little noticed outside the industry. All that changed following DeepSeek’s exploits earlier this year, which put international attention on pockets of innovation in China — with growing global implications. https://lnkd.in/e-98Xh9Z