Tag: Medication

Posted on

A Two-Part Intervention to Target Cardiovascular Health

Conditions: Autism; Adverse Childhood Experience; Stress; Cardiovascular (CV) Risk

Interventions: Behavioral: Lifestyle Medicine; Behavioral: Cognitive Behavioral Therapy (CBT); Behavioral: Lifestyle Medicine with CBT Group

Sponsors: University of California, Los Angeles; Health Resources and Services Administration (HRSA)

Not yet recruiting
Posted on

Insilico, SK Launch Up-to-$2.5B Neuroimmune AI Drug Collaboration

Insilico Medicine will partner with SK Biopharmaceuticals to discover new artificial intelligence (AI)-based drug candidates for disorders affecting the neuroimmune area of the central nervous system (CNS), through a collaboration that could generate up to $2.5 billion for the AI-based drug developer.

Insilico agreed to apply its Pharma.AI platform, which addresses target validation, generative chemistry, and molecule optimization, along with its preclinical drug discovery expertise, to discover, design, and optimize candidates for neuroimmune indications against targets that will originate with SK.

SK will contribute its development and clinical capabilities in neuroimmune disorders, steering the late-stage development and commercialization of all resulting programs.

“Some of the collaborations we do are very focused on target discovery, but here it’s more focused on the delivery of the real drug,” Alex Zhavoronkov, PhD, Insilico’s founder, co-CEO, and chief business officer, told GEN in an interview at his company’s exhibition-hall booth during the Biotechnology Innovation Organization (BIO) International Convention, held recently in San Diego.

“Basically, we are being brought in to develop a drug, to discover and take it to a certain point, after which the partner takes it over. And they usually have a lot of choices to do it with other partners,” Zhavoronkov explained. “But they trust AI. They like AI. They like the way we design drugs and like our speed and efficiency.”

Headquartered in Seongnam, South Korea, SK Biopharmaceuticals is a global biotech focused on the research, development, and commercialization of new therapies for CNS disorders and beyond, including radiopharmaceutical and targeted protein degradation therapies. In 2020, SK became the first Korean pharma to independently develop and commercialize a novel drug in the United States, the epilepsy treatment Xcopri® (cenobamate), after it won FDA approval a year earlier.

Beyond epilepsy

“This collaboration represents an important milestone in expanding our growth beyond epilepsy into new CNS therapeutic areas, building on the deep CNS expertise we have established through the successful development and commercialization of cenobamate,” Donghoon Lee, SK Biopharmaceuticals’ president and CEO, said in a statement. “By combining Insilico’s AI-powered drug discovery platform with SK Biopharmaceuticals’ clinical development and U.S. commercialization capabilities, we believe we can accelerate the discovery of innovative CNS therapies for patients.”

“Beyond a single program, we see this collaboration as a scalable and repeatable growth platform that can be leveraged for future target discovery and development opportunities,” Lee added.

SK Biopharmaceuticals is part of the SK Group, South Korea’s second-largest family-owned chaebol or conglomerate, after Samsung Group, and a chaebol whose holdings include the vaccine developer SK Bioscience, the contract development and manufacturing organization (CDMO) SK Pharmteco, and SK Hynix, a supplier of high bandwidth memory (HBM) chips that power the AI processors of Nvidia and AMD. SK Hynix and a sister chaebol company, SK Telecom, are investors in Rebellions, a Korean dedicated fabless design company specializing in manufacturing AI neural processing units optimized for data centers and large language models.

Insilico’s AI-based drug development background complemented SK’s focus on leveraging AI and digital technologies across drug discovery, development, and treatment, SK Biopharmaceuticals concluded.

“Very difficult space”

“After you have done this,” Zhavoronkov said, pointing to a graphic showing Insilico’s AI-based pipeline, “people know that we can do this. The question is, can we do it in neuroimmunology? That is a very difficult space, one of the most difficult disease areas to tackle, given the need to develop molecules with properties that include high levels of safety and brain penetration.”

Insilico’s pipeline includes one candidate designed to treat CNS disorders—ISM8969, a Phase I oral brain penetrant NLRP3 inhibitor, which the company is co-developing with Hygtia Therapeutics under an exclusive global license and co-development collaboration. Both companies hold 50% worldwide rights to ISM8969, with Insilico eligible to receive up to $66 million in upfront and milestone payments from Hygtia, an incubatee of Shenzhen Pengfu Fund of Fosun Health Capital and Fosun Pharma.

Insilico is leading initial clinical development of ISM8969, from IND submission through execution of the Phase I trial (NCT07581431) for the drug’s initial indication of Parkinson’s disease. Hygtia will lead subsequent global clinical studies, regulatory submissions, and commercialization activities.

Discovered using the company’s generative AI platform Chemistry42, ISM8969 has shown strong efficacy, favorable safety, and robust blood-brain barrier (BBB) penetration, leading to marked anti-inflammatory activity in preclinical studies, according to Insilico.

Unlike other drug developers that concentrate on a few therapeutic areas, Insilico maintains a pipeline of 40+ programs across a wide variety of indications, including idiopathic pulmonary fibrosis (IPF), cancer, obesity and metabolic diseases, pain, and inflammatory diseases, including inflammatory bowel disease.

Longevity focus

“We focus on aging. That’s what we care about,” Zhavoronkov declared. “Most of the programs that we like to work on are focused on longevity.”

Furthest along in clinical studies is rentosertib (formerly called ISM001-055), a small molecule designed to treat idiopathic pulmonary fibrosis (IPF) by targeting Traf2- and NCK-interacting kinase (TNIK), a serine/threonine kinase whose activation plays a crucial role in cellular processes that include signal transduction pathways essential for fibrosis development.

Rentosertib has completed a 12-week Phase IIa trial (NCT05938920) conducted across 22 sites in China, with results published in Nature Medicine, and is in a separate Phase II trial in the United States. In the Chinese trial, rentosertib met its primary endpoint of safety and tolerability across all dose levels, and showed positive results for the secondary efficacy endpoint, wherein a dose-dependent forced vital capacity (FVC) improvement was seen.

“We’re preparing for the next step. When that gets announced, it’s going to be a big deal. Hopefully sooner than later. Like, much sooner than much later,” Zhavoronkov said.

As in later this year?

“It’s in the second half, but maybe closer to the earlier second half,” he replied.

The U.S. trial has not progressed as quickly as the Chinese trial. “We have not seen a trial slower than that in our history. Enrollment is just extremely slow because our criteria for enrollment are very high. Also, there are not that many [IPF] patients compared with China, where it was just much faster,” Zhavoronkov said.

Given the slow speed of the U.S. trial, he said, it would be more worthwhile to just start a Phase IIb or Phase III following more data from China. “It’s a game of chess, so to speak. You need to time it [an additional trial], and you need to properly adjust to the realities of enrollment.”

In April, Insilico received investigational new drug (IND) clearance from China’s Center for Drug Evaluation (CDE) to begin a Phase I study of inhalable rentosertib in IPF—the company’s 13th pipeline program to receive IND clearance. The study will evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of rentosertib inhalation solution—first through a randomized, double-blind, placebo-controlled trial in healthy participants involving single and multiple ascending dose cohorts; then through a non-randomized, open-label evaluation in IPF patients who will receive multiple doses. Approximately 80 people are expected to be enrolled.

“Most promising”

“IPF is the most promising disease for longevity therapeutic testing because the patients are old. And even normal people up to 65, they start losing force valve capacity quite a bit, like the amount of air you can breathe out of your lungs. And it’s like 30, 40 milliliters a year. IPF patients can lose up to 400 milliliters,” Zhavoronkov said. “That’s the critical measure of lung function, and that’s what we measure in the study.”

Insilico researchers chronicled the drug’s discovery and early development in Nature Biotechnology in March 2024, detailing a novel target discovered by Insilico’s target identification engine, PandaOmics, and a novel molecular structure designed by its generative chemistry engine, Chemistry42. Both are specific-function platforms within the company’s AI platform, Pharma.AI.

“We are making massive progress on the AI side,” Zhavornkov said.

Massive enough that users should expect to see either tweaks in the platform or new platforms? “100%, you’re going to see a complete rewall,” he replied, as in a secure, self-contained AI environment or “walled garden” pursued by AI developers during commercial inflection points.

“We have so many new next-generation tools right now that it’s actually very difficult to productize them. Because at the lab level and at the platform level, we see superintelligence already. I’m talking about, we can probably go from prompt to drug in some areas: You basically prompt it, and you could make it and potentially take it,” Zhavoronkov explained. “I think we’re there. It’s just, fortunately, you have to do all the nitty-gritty testing and then clinical studies.”

Insilico’s other Phase II program is ISM5411, a gut-restricted molecule designed to treat inflammatory bowel disease (IBD) by taking aim at another anti-aging target, PHD 1/2. Unlike with rentosertib, clinical studies for the PHD1/2 inhibitor have found it easier to recruit patients in the United States than in China, where fewer patients are diagnosed with the disease.

The program, formerly called ISM012-042, was shown in preclinical studies to restore intestinal barrier function and alleviate gut inflammation in multiple experimental colitis models, while exhibiting favorable safety and pharmacokinetic profiles, according to a 2024 study published in Nature Biotechnology. The program is one of two that target PHD 1/2; the other is a small molecule designed to treat anemia of chronic kidney disease, for which Greater China rights have been outlicensed to TaiGen.

Longevity-linked targets

PHD 1/2, TNIK, and NLRP3 are three of numerous longevity-linked targets for the drug candidates within Insilico’s growing pipeline. Among the others that are targets of candidates in the clinic or IND-cleared:

  • ENPP1 (ectonucleotide phosphodiesterase 1), a target of a program designed to treat anti-PD-1/-L1 resistant cancers, and has won IND clearance.
  • KAT6 (lysine acetyltransferase 6 ) and KIF18A (kinesin family member 18A), targets of MEN2312 and MEN2501, respectively, are both Phase I cancer-fighting candidates outlicensed to Menarini Group through collaborations launched in 2024 and 2025.
  • MAT2A (methionine adenosyltransferase 2α), a target of a Phase I small molecule candidate designed to treat MTAP -/- (methylthioadenosine phosphorylase deficient) cancer.
  • QPCTL (glutaminyl-peptide cyclotransferase-like protein), a target of a first-in-class Phase I oral small molecule cancer immunotherapy for cold tumors being co-developed in partnership with Fosun.
  • TEAD (transcriptional enhanced associate domain), a target of ISM6631, a Phase I “pan-TEAD” (TEAD 1/2/3/4) inhibitor designed to treat mesothelioma and solid tumors that include epithelioid hemangioendothelioma (EHE), meningioma, glioblastoma, liposarcoma, and pancreatic cancers.
  • USP1 (ubiquitin-specific protease 1), a target of a Phase I BRCA-mutated cancer drug outlicensed to Exelixis under a 2023 collaboration.

“Our differentiation from everybody else is novelty—novelty of the target,” Zhavoronkov said. “Nobody I know in our industry has such a large number of absolutely novel targets that have never been in the clinic before or that are novel for indication. But with novelty comes a great risk. And pharma doesn’t want to take that risk up until a certain point.”

“Very often, you need to spend a long time in the process of discovery and then development in order to license a drug,” he added. “Once you license a drug, usually in Insilico’s case, some of the pharma companies actually like to get some access to AI technologies, and then it would be structured as a licensing class collaboration.”

Second multi-billion-dollar collaboration

SK Biopharmaceuticals is the second multi-billion-dollar collaboration announced by Insilico this year. The first was an up-to-$2.75 billion discovery and development partnership with Eli Lilly, to which Insilico granted an exclusive global license to develop, manufacture, and commercialize what the companies described in an announcement only as “potentially best-in-class, novel oral therapeutics in preclinical development for certain indications,” without detailing the therapeutic areas where the companies plan to partner.

“Those are early preclinical drugs that have incredible properties. I like to use the term maximally multi-parameter optimized molecule or MMOMs,” Zhavoronkov said.

Lilly agreed to pay Insilico $115 million upfront, as well as development, regulatory, and commercial milestones plus tiered royalties on future sales. The deal continued and expanded a relationship that began late in 2023, when Lilly inked a licensing agreement allowing it to access Insilico’s Pharma.AI software suite.

The Lilly collaboration will allow Insilico and Zhavoronkov to work with Jiye Shi, PhD, the pharma giant’s senior vice president of discovery technology & platforms and early molecule discovery, who has specialized in research on integrating machine learning and AI into the pharmaceutical pipeline. Previously at UCB, he led a computational biology team that used machine learning and computational design to create bimekizumab, a humanized interleukin-17A and F antagonist hailed as one of the first, if not the first, AI-based dual-targeting monoclonal antibodies to reach the market, where it is sold as Bimzelx® (bimekizumab-bkzx).

In February, Shi and Zhavoronkov co-authored a paper outlining a vision for a “prompt-to-drug” pipeline, where AI not only generates novel hypotheses and designs optimized drug candidates but also orchestrates synthesis, validation, and clinical planning in a closed-loop system.

“The realization of a true ‘prompt-to-drug’ pipeline, in which a natural language request initiates a fully autonomous drug development program, is no longer a distant aspiration. With the development of modular AI platforms, humanoid-in-the-loop robotics, and multi-agent systems, the foundational components for this vision are already operational,” wrote Shi, Zhavoronkov, and co-author David Gennert, PhD, a medical writer who at the time was Insilico’s senior scientific writer and editor.

Insilico’s collaboration with SK, Zhavoronkov said, reflects how AI “has transformed from being a fairy tale or a promise, to being a real tool that is used routinely to discover and develop drugs.”

“This is basically production level,” he added. “We’re not trying to do a pilot here.”

The post Insilico, SK Launch Up-to-$2.5B Neuroimmune AI Drug Collaboration appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Women with Parkinson’s Have More Amyloid Plaques than Men

A study led by the Mayo Clinic Arizona shows women with Parkinson’s disease have greater amyloid plaque burden than men with the condition, even after controlling for factors like carriage of the APOE4 Alzheimer’s disease susceptibility gene variant.

As reported at the European Academy of Neurology Congress in Geneva this week, 57% of women included in the study had a high amyloid plaque burden versus 40% of the men.

Amyloid-beta is a protein fragment that normally gets cleared from the brain. In Alzheimer’s disease, it misfolds and aggregates into oligomers and plaques between neurons. This disrupts synaptic signaling, activates neuroinflammation, and promotes tau protein hyperphosphorylation into neurofibrillary tangles as the disease progresses.

In contrast, Parkinson’s disease is caused by the misfolding and clumping of a protein called alpha-synuclein into toxic deposits known as Lewy bodies, which build up in and destroy the neurons that produce dopamine in a brain region called the substantia nigra. While Parkinson’s is known for its characteristic motor symptoms, at least 25% also have dementia-like symptoms similar to those seen in Alzheimer’s disease. Amyloid beta plaques are thought to worsen Parkinson’s disease and increase the risk of dementia symptoms.

There are known differences in the prevalence and symptoms shown by men and women with Parkinson’s disease. To investigate this further, 230 people enrolled in the Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program were included in this study after death. Amyloid burden in the brain was assessed during autopsy. Other clinical factors such as cognition and symptoms were recorded prior to death.

The study found that amyloid plaque burden in women was higher than in men with Alzheimer’s. For example, mean cortical total plaque score in women was 6.5/15 vs 4.9/15 in men. Neuritic plaque density was also higher in women at 1.7/3 compared with 1.3/3 in men.

After correcting for age at death and APOE4 status, women in the study were more than twice as likely to have a high plaque burden than men.

This did not seem to translate to cognitive differences between men and women in the study though. “Men and women with Parkinson’s disease had similar rates of Alzheimer’s dementia and similar results on cognitive testing. However, women showed a higher amyloid plaque burden compared with men,” explained presenting author Erika Driver-Dunckley, MD, Mayo Clinic Arizona, in a press statement.

Notably, in standard Parkinson’s disease, men are at higher risk of developing dementia than women, so it is possible women have some protection from alpha-synuclein-driven decline but not from damage linked to amyloid accumulation. Women with Parkinson’s also live longer than men with the condition, as well as being more prone to amyloid buildup and Alzheimer’s disease, which complicates understanding the meaning of these results.

“Our findings highlight the need for further research into sex differences in Parkinson’s disease and Alzheimer’s-related pathology,” concluded Driver-Dunckley. “An important next step will be to confirm these findings in additional large clinicopathological studies and better understand the biological mechanisms that may underlie these differences.

The post Women with Parkinson’s Have More Amyloid Plaques than Men appeared first on Inside Precision Medicine.

Posted on
<![CDATA[Expert shares ADHD medication sequencing tips and practical insomnia strategies, from stimulants to melatonin, for kids and adults.]]>
Posted on

VR Rehabilitation Improves Arm and Hand Movement After Stroke

A new rehabilitation platform combining virtual reality (VR) and nerve stimulation significantly improved the recovery of arm and hand function after a stroke compared to conventional rehabilitation approaches. Published today in Nature Medicine, results from a small-scale clinical study show early promise for a more effective and accessible rehabilitation approach that can be personalized to each patient’s needs. 

Approximately 60% of stroke survivors develop long-term disability affecting their mobility. Even after extensive physiotherapy and occupational therapy, many continue to live with reduced arm and hand function, which severely impacts their ability to perform day to day tasks and live independently. 

“Our aim was to go beyond mere movement training,” said Stanisa Raspopovic, PhD, professor of biomedical engineering at the Medical University of Vienna and senior author of the study. “After a stroke, patients often have difficulty not only moving the affected limb, but also feeling it and perceiving it correctly. MultiSensy was developed to reconnect movement, sensation and body awareness during rehabilitation.” 

The MultiSensy rehabilitation platform combines immersive VR with electrical nerve stimulation. The VR goggles present users with interactive virtual tasks designed to train arm and hand functions such as reaching, grasping, pinching, and forearm rotation. Meanwhile, electrodes on the skin stimulate sensory nerves in real time to make patients feel virtual objects as if they were physically touching them. 

The system was tested on a cohort of 34 patients who had suffered a stroke over three months before. Participants were divided into two groups who were treated either with MultiSensy or conventional rehabilitation including physiotherapy and occupational therapy. Both groups completed a total of 12 training sessions over the course of three weeks. 

Patients who used the VR system saw a greater recovery of arm and hand movement compared to those in the control group, achieving nearly twice the improvement according to a standard assessment of motor impairment after stroke. In addition, MultiSensy was able to address body awareness and sensory deficits caused by stroke, which are often left aside by conventional rehabilitation strategies.  

“After a stroke, some patients struggle to feel touch in their affected hand and may even perceive the arm as distorted in size, shape, or position,” said Valerio Aurucci, PhD, lead author of the study and former graduate student at ETH Zurich. “Participants treated with the new system showed improvements in their sense of touch and in perception of their affected arm.”

Another advantage of the MultiSensy platform is that each task can be adapted to the impairment level of the user, tailoring treatment to their unique needs. The VR system collects movement data during training, providing objective measurements of progression that clinicians can rely on to monitor a patient’s performance and recovery over time.

“The results provide early clinical evidence that immersive virtual reality combined with sensory nerve stimulation can support recovery after stroke, even after months from the event”, said Raspopovic. “The technology is still at the research stage, and larger clinical trials are needed to confirm its benefits. However, the study opens a promising perspective for future personalized and potentially home-based stroke rehabilitation.”

The post VR Rehabilitation Improves Arm and Hand Movement After Stroke appeared first on Inside Precision Medicine.

Posted on

Intravesical CAR T-Cell Therapy Reduces Bladder Cancer Growth in Preclinical Model

Researchers at Weill Cornell Medicine and Roswell Park Comprehensive Cancer Center have genetically engineered CAR T cells that specifically target and kill bladder cancer (BCa) cells. Through their preclinical study the team, co-led by Taha Merghoub, PhD, a professor at Weill Cornell Medicine, identified the protein MUC16 as a clinically relevant target for bladder cancer, and demonstrated that direct delivery of MUC16-targeting CAR T cells into the bladder via a catheter can control bladder tumors in mice. The investigators say their study raises hopes that a similar approach may be effective in humans.

The team reported on their results in Journal of Experimental Medicine, in a paper titled “Intravesical mesothelin-based CAR T cells targeting MUC16 effectively control bladder cancer in preclinical models,” concluding that their findings “… not only establish MUC16 as a clinically relevant target for anti-BCa CAR T-cell therapy, but also suggest that intravesical delivery, a commonly used administration route in urological practice, represents a viable, easy-to-implement, and more effective strategy of antitumoral adoptive CAR T-cell transfer.”

Approximately 600,000 new cases of bladder cancer are diagnosed worldwide each year, causing nearly 200,000 deaths, the authors wrote. Treatment generally involves surgical removal of the tumor followed by chemotherapy or immunotherapy. But these approaches are associated with high recurrence and progression rates, often necessitating complete removal of the bladder, a life-altering procedure that can lead to significant complications. “Intravesical therapies are the mainstay of bladder cancer (BCa) management, but their efficacy is limited by toxicities and recurrences,” they continued. “Given these challenges there is a significant unmet clinical need, driving renewed interest in bladder-sparing therapies for patients with high-risk bladder cancer who are unfit or unwilling to have their bladder removed,” Merghoub said.

CAR T cells are immune cells genetically engineered to express an artificial receptor protein capable of specifically targeting cancer cells. This type of immunotherapy has been successfully used to treat many different types of blood cancer. But success against solid tumors has so far been limited due to challenges that include poor tumor infiltration and off-target toxicity. Merghoub and colleagues attempted to overcome these issues by creating CAR T cells with high specificity for bladder cancer cells and then delivering them directly to the bladder via a catheter, known as intravesical delivery.

The team developed an antigen discovery pipeline, through which they identified MUC16 as a promising BCa target. “In this study, we leveraged a computational antigen-identification pipeline, which prioritized high tumor specificity and minimal pan-tissue expression to rationally identify MUC16 as a potential target for BCa-directed CAR T-cell therapy,” they stated. The researchers also noted that MUC16 and its soluble form, CA-125, have previously been identified as prognostic biomarkers for BCa, and MUC16 has been investigated as a CAR T-cell therapy target in other malignancies, and particularly ovarian cancer.

Through their newly reported study the investigators found that MUC16 is highly expressed on the surface of many bladder cancer cells, including types that are resistant to existing therapies, but is largely absent from normal bladder cells and other healthy tissues. “Given its favorable expression profile, absence in normal bladder, and high expression across a broad spectrum of bladder tumors analyzed collectively spanning a total of 1,292 patients, including those recalcitrant to existing therapies, MUC16 was selected as the lead candidate for BCa-specific CAR T-cell therapy development,” they wrote.

The researchers then generated CAR T cells that target MUC16. In initial tests these CAR T cells were able to kill MUC16-positive tumors grown in the lab from patient-derived bladder cancer cells. Merghoub and colleagues then tested the ability of the MUC16-targeting CAR T cells to control the growth of human bladder cancer cells implanted in the bladders of mice. The team found that the CAR T cells were ineffective when administered intravenously, but when delivered intravesically, they reduced tumor growth and extended survival. When administered directly into the bladder, the CAR T cells were unable to spread into the rest of the body, minimizing the risk of any side effects in other tissues. “Intravesical delivery of these CAR T cells reduced the growth of BCa xenografts and prolonged survival in xenograft-bearing mice, showing superior efficacy compared with typical systemic CAR T-cell administration,” the investigators noted.

“Development of engineered T cells for solid tumors has been challenging, in part due to normal tissue expression of potential target antigens,” Wolchok says. “Using a compartmentalized delivery system allows us to overcome this hurdle and hopefully come one step closer to broader use of CAR and transgenic T cells for common solid tumors, like bladder cancer.”

“Our findings establish MUC16 as a clinically relevant target for CAR T-cell therapy in bladder cancer, and highlight that intravesical delivery, a commonly used administration route in urological practice, represents a feasible, effective, and readily easy-to-implement strategy for adoptive CAR T-cell transfer,” Merghoub said. “This approach could be useful for both initial treatment of bladder cancer as well as treatment refractory subsets of tumors, offering an attractive therapeutic option for patients who may have limited therapeutic alternatives besides bladder removal.”

In their paper the team also suggest that their findings “… lay the groundwork for refining CAR T-cell therapies targeting other antigens for BCa.”

The post Intravesical CAR T-Cell Therapy Reduces Bladder Cancer Growth in Preclinical Model appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Nipah and Hendra Viruses: Antibody Cocktail Provides Complete Protection in Hamster Model

Nipah virus—and the closely related Hendra virus—are zoonotic pathogens causing severe respiratory and neurological disease with high mortality rates. Outbreaks are rare but often devastating, with mortality rates ranging from 40 to 75 percent. There are no approved human vaccines or therapeutics for people infected with these viruses.

Now, an international research team led by investigators at the Icahn School of Medicine at Mount Sinai has developed the first fully human monoclonal antibody cocktail shown to provide complete protection against Nipah and Hendra virus infection—even when treatment was given after infection had begun. The findings represent an important step toward developing the first antibody-based therapy for Nipah virus and establish a promising strategy for combating emerging infectious diseases.

This work is published in Science Translational Medicine, in the paper, “A cocktail of human mAbs targeting the henipavirus fusion and receptor binding proteins provides cross-species neutralization.”

“One of the biggest challenges in developing treatments for henipaviruses is that human survivor samples are extremely rare,” said Axel Guzman-Solis, a graduate student in the Department of Microbiology at the Icahn School of Medicine. “We wanted to determine whether we could create fully human antibodies that target the virus in multiple ways at once, making it much more difficult for the virus to evolve resistance.”

The researchers used vaccinated humanized mice with the fusion protein (F) and receptor binding protein (RBP) of Nipah virus with the goal of isolating monoclonal antibodies. The investigators discovered two antibodies, 8G3 and 2A1, which targeted the RBP and F proteins, respectively, and together, could neutralize the virus and limit the potential for immune escape. Because the antibodies work through independent mechanisms, they create multiple barriers to infection and make it more difficult for the virus to develop resistance.

Using cryo-EM, the researchers discovered that the 2A1 antibody neutralizes the virus by stabilizing a sugar-containing structure on the viral fusion protein rather than displacing it, as scientists had anticipated. This previously unrecognized strategy may help explain the antibody’s potency and resilience against viral escape.

“We were surprised to find that the antibody essentially embraces a structure on the virus that many antibodies try to move out of the way,” said Benhur Lee, MD, chair in microbiology at the Icahn School of Medicine. “The finding suggests that stabilizing a viral protein can sometimes be just as effective—or even more effective—than disrupting it.”

When administered together, the antibody cocktail completely protected hamsters from lethal Nipah virus infection. The treatment remained effective even after infection was established, an encouraging result for a disease that progresses rapidly and carries a high fatality rate.

The findings may have broader implications for pandemic preparedness. Because many viruses rely on multiple proteins to infect cells, the researchers believe this dual-targeting strategy could be adapted for other high-priority pathogens.

“This work provides a blueprint for developing antibody therapies that are more resistant to viral evolution,” said Lee. “Rather than relying on a single target, we can attack a virus at multiple vulnerable points simultaneously.”

Next steps include studies in nonhuman primates, evaluation of long-term safety, and efforts to optimize the antibodies for clinical use. The team is also exploring next-generation antibody formats, including single molecules capable of targeting multiple viral proteins simultaneously, as well as approaches that could broaden protection against additional members of the henipavirus family.

“As zoonotic outbreaks continue to emerge around the world, there is an urgent need for therapies that can be deployed quickly against high-consequence pathogens,” said Lee. “Our long-term goal is to translate these discoveries into practical tools that help protect people during future outbreaks.”

The post Nipah and Hendra Viruses: Antibody Cocktail Provides Complete Protection in Hamster Model appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Efficacy and predictors of cognitive stimulation therapy combined with pharmacotherapy for mild-to-moderate Alzheimer’s disease: a randomized controlled trial

IntroductionAlzheimer’s disease (AD) is associated with progressive cognitive decline, functional impairment, and reduced quality of life. Although pharmacological treatments such as cholinesterase inhibitors and memantine are commonly used, their clinical benefits remain limited and heterogeneous. Cognitive stimulation therapy (CST) may provide additional benefits when combined with standard pharmacotherapy. This randomized controlled trial (RCT) aimed to evaluate the clinical efficacy of modified CST combined with standard drug therapy on cognitive function, activities of daily living, and quality of life in patients with mild-to-moderate AD and to explore key predictors of CST efficacy using a multivariate regression model.MethodsThis evaluator-blinded randomized controlled trial enrolled 80 patients with mild-to-moderate Alzheimer’s disease (AD), who were randomly assigned in a 1:1 ratio to either the modified CST plus standard pharmacotherapy group (study group, n = 40) or the standard pharmacotherapy-alone group (control group, n = 40).The modified CST program comprised 14 weekly 45-minute sessions. The primary endpoint was the change in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) score from baseline to post-intervention. Secondary measures included the Activities of Daily Living (ADL) scale and the Quality of Life in Alzheimer’s disease (QOL-AD) questionnaire. Data were analyzed using an intention-to-treat (ITT) approach. Independent predictors of treatment efficacy were identified using a two-stage screening strategy (univariate screening and stepwise regression).ResultsA total of 75 patients completed the study, and 80 were included in the ITT analysis. After 14 weeks of intervention, baseline-adjusted ANCOVA showed that the study group had significantly better post-intervention ADAS-Cog scores than the control group. The adjusted mean difference in ADAS-Cog score was -3.28 points (95% CI: -3.72 to -2.83; P < 0.001), favoring the study group. Significant baseline-adjusted between-group differences were also observed for ADL (adjusted mean difference = -4.93, 95% CI: -8.39 to -1.47; P = 0.006) and QOL-AD (adjusted mean difference = 2.69, 95% CI: 1.01 to 4.37; P = 0.002), both favoring the study group. Higher years of education (β = -0.54, P < 0.001), regular physical activity (β = -0.28, P = 0.003), higher baseline Mini-Mental State Examination (MMSE) scores (β = -0.22, P = 0.001), and active hobbies (β = -0.20, P = 0.002) were significant independent predictors of CST efficacy.DiscussionModified CST combined with medication significantly delays cognitive decline and improves QOL-AD in patients with mild-to-moderate AD. Educational attainment, lifestyle factors, and cognitive reserve are key determinants of CST efficacy. Relevant institutions should develop targeted enhancement protocols for patients with lower educational levels or insufficient cognitive reserves when implementing CST.Trial RegistrationChinese Clinical Trial Registry, identifier ChiCTR2600118654, https://www.chictr.org.cn.