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Yahoo
3 days ago
- Health
- Yahoo
Publication in Alzheimer's & Dementia Elucidates Multimodal Mechanism of Action Underpinning Promising New Neuromodulation Therapy for Alzheimer's
Review publication details benefits of repetitive transcranial magnetic stimulation (rTMS) on Alzheimer's, including increases in neuroplasticity and other structural and functional second order impacts on the brain Seminal publication on rTMS in Alzheimer's authored by Sinaptica scientific co-founders along with other experts in neuromodulation and Alzheimer's disease CAMBRIDGE, Mass., June 18, 2025--(BUSINESS WIRE)--Sinaptica Therapeutics, Inc., a clinical-stage company leading the development of a new class of personalized neuromodulation therapeutics to treat Alzheimer's and other primary neurodegenerative diseases, today announced that a comprehensive review article published in the peer-reviewed journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association delivers a landmark synthesis of evidence that positions repetitive transcranial magnetic stimulation (rTMS) as a scientifically grounded, non-invasive therapeutic strategy for Alzheimer's disease (AD). The publication, "The Neurobiological Foundation of Effective Repetitive Transcranial Magnetic Brain Stimulation in Alzheimer's Disease," was authored by a multidisciplinary team led by Sinaptica scientific co-founder Dr. Giacomo Koch of the Santa Lucia Foundation, University of Ferrara, and the Italian Institute of Technology. Drawing on foundational models and recent clinical and animal data, the article charts how rTMS modulates biological systems across multiple levels—molecular, cellular, synaptic, and network-wide—to address core mechanisms of neurodegeneration. "Our goal with this publication is to consolidate the preclinical and clinical findings to explain why rTMS isn't just symptomatic—it is actually disease modifying. This gives us a foundational understanding of how stimulation protocols can directly modulate neurotransmission, reduce inflammation, enhance plasticity, and even promote clearance of toxic proteins," said Giacomo Koch, MD, PhD, Sinaptica scientific co-founder, Neurologist, Professor of Physiology, University of Ferrara, and Director, Non-Invasive Brain Stimulation Laboratory, Santa Lucia Foundation. The publication reviews the evidence supporting the fundamental mechanisms of action of rTMS treatments in AD. rTMS exerts profound effects from the micro-molecular scale to the macro network-level scale. By engaging distinct pre- and post-synaptic structures within the stimulated neural network, it directly and indirectly influences various cellular and molecular components. These effects work together to stabilize and improve brain function through the following means: Strengthens Neuronal Structures - Upregulates neurotrophic factors e.g. BDNF, leading to neuronal structural changes e.g. via remodeling of dendritic spines. Strengthens Synapses - Modulates neurotransmitter circuits, both through increased production and sensitivity of dopaminergic-, glutamatergic-, and GABA-ergic pathways. Neuroinflammation - Mitigates neuroinflammation by reducing microglial activation and pro-inflammatory cytokines release e.g. by promoting glutamate reuptake. Amyloid - May counteract beta amyloid overproduction and toxic aggregation by interrupting a vicious cycle of hyperexcitability. Tau - Potentially reduces tau hyperphosphorylation and accumulation via the GSK-3β pathway. Clearance - Potentially increases glymphatic clearance of toxic proteins. All of the above mechanisms contribute to restoring network-wide excitation/inhibition imbalance, restoring LTP-like mechanisms of neuroplasticity, and enhancing large-scale connectivity. Authors of this definitive paper are Giacomo Koch (Experimental Neuropsychophysiology Lab, Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS), Emiliano Santarnecchi (Gordon Center for Medical Imaging, Mass General Research Institute; Harvard Medical School), Harald Hampel (Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital), Annibale Antonioni (Department of Neuroscience and Rehabilitation, University of Ferrara), and Alessandro Martorana (Memory Clinic, Department of Systems Medicine, University of Tor Vergata). "Based on this new publication, repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus in the brain's central Default Mode Network is an emerging element of precision medicine in neurology. Based on accumulating basic, translational, and clinical evidence, this standardized targeted non-invasive electro-magnetic brain stimulation will likely be part of the evolving clinical care landscape with different treatments and combinations," said co-author Dr. Harald Hampel, a leading international brain researcher and Alzheimer's disease (AD) scientist. "Further clinical studies are warranted to benefit the globally increasing population of AD patients." As the field moves toward more personalized and mechanistically distinct Alzheimer's therapies, this review provides a vital reference point for researchers, clinicians, and innovators. It supports the integration of rTMS into a precision medicine framework that could transform how providers manage Alzheimer's—potentially shifting the paradigm from reactive care to proactive, highly tailored, connectome-level intervention, including combination therapies. "We are beginning to see rTMS emerge as a safe, scalable precision medicine platform for Alzheimer's," said Emiliano Santarnecchi, PhD, co-founder of Sinaptica Therapeutics, Associate Professor of Radiology & Neurology at Harvard Medical School, as well as Director, Precision Neuroscience & Neuromodulation Program and Director, Network Control Laboratory, at Massachusetts General Hospital in Boston, MA. "This is not just about stimulating the brain—it's about rewiring disease-affected networks with intention and scientific precision." The publication establishes the translational relevance of these findings, citing Phase 1 and 2 human trials in which targeted, neuronavigated rTMS protocols have boosted memory, stabilized cognitive performance, restored functional brain connectivity, and enhanced gamma rhythm activity—key markers of brain health. These protocols, particularly those focused on the Default Mode Network (DMN), are seen as promising interventions for mild cognitive impairment and Alzheimer's. "This definitive reference illuminates an evolving paradigm shift away from simplistic linear 'nerve stimulation' toward the new and rapidly progressing field of 'network modulation," said Ken Mariash, CEO of Sinaptica Therapeutics. "This publication presents a higher order systems-level approach to how we think about and treat brain diseases. Sinaptica's nDMN therapy induces a cascade of network-wide effects that compound, ultimately restoring the exquisite balance of the networks involved in memory and cognition. In this new context, we can better understand how it was possible to achieve such strong and consistent clinical outcomes in previous Phase 2 trials in mild/moderate Alzheimer's patients. This important publication reinforces everything we're building at Sinaptica by elucidating the neurobiological mechanisms underlying our therapy and validating the importance of targeting the brain's network-level dysfunction with both precision and personalization." About the SinaptiStim® SystemThe SinaptiStim® System is an investigational new approach to treating Alzheimer's disease using non-invasive personalized precision neuromodulation. Calibrated to each individual's brain, the therapy is delivered in weekly 20-minute sessions in a recliner. The SinaptiStim system delivers safe, painless, customized neurostimulation technology targeting the Default Mode Network (DMN), an important brain network associated with episodic memory, introspection, and other cognitive functions. The technology was granted Breakthrough Device Designation by the FDA in 2022. The company is preparing for a pivotal randomized controlled clinical trial in mild-to-moderate Alzheimer's. In this trial, the treatment will be calibrated quarterly using TMS and EEG concurrently in combination with MRI-guided neuronavigation, which enables the SinaptiStim System to achieve customized precise repeatable targeting and safe-yet-effective dosage for each patient, tracking progress and adjusting over time to achieve the best possible individualized outcomes with its nDMN therapy. The pivotal trial will also be designed to determine the effects of SinaptiStim® System on several biomarkers measuring beta amyloid, phosphorylated tau, neuroinflammation, and synaptic dysfunction. About Sinaptica TherapeuticsSinaptica Therapeutics is a clinical-stage neuromodulation therapeutics company leading the development of a new class of novel personalized therapeutics to revolutionize the treatment of Alzheimer's and other primary neurodegenerative diseases. The company utilizes a patented non-invasive approach to treating Alzheimer's via precision neurostimulation of a key brain network involved in memory, the Default Mode Network. Sinaptica's scientific co-founders pioneered research on this novel approach which a growing body of evidence indicates can slow disease progression. Sinaptica's mission is to bring a safe, effective, and non-invasive neuromodulation therapy to Alzheimer's patients that can help to significantly slow the progression of cognitive, functional, and behavioral decline. Learn more at and follow us on LinkedIn and X @SinapticaTX. The SinaptiStim® System is for investigational use only. It has not been approved by the U.S. Food and Drug Administration and is not available for commercial sale in any geography. View source version on Contacts Kathryn Morris, BrightPointkathryn@ 914-204-6412 Sign in to access your portfolio
Business Wire
3 days ago
- Health
- Business Wire
Publication in Alzheimer's & Dementia Elucidates Multimodal Mechanism of Action Underpinning Promising New Neuromodulation Therapy for Alzheimer's
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Sinaptica Therapeutics, Inc., a clinical-stage company leading the development of a new class of personalized neuromodulation therapeutics to treat Alzheimer's and other primary neurodegenerative diseases, today announced that a comprehensive review article published in the peer-reviewed journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association delivers a landmark synthesis of evidence that positions repetitive transcranial magnetic stimulation (rTMS) as a scientifically grounded, non-invasive therapeutic strategy for Alzheimer's disease (AD). The publication, ' The Neurobiological Foundation of Effective Repetitive Transcranial Magnetic Brain Stimulation in Alzheimer's Disease,' was authored by a multidisciplinary team led by Sinaptica scientific co-founder Dr. Giacomo Koch of the Santa Lucia Foundation, University of Ferrara, and the Italian Institute of Technology. Drawing on foundational models and recent clinical and animal data, the article charts how rTMS modulates biological systems across multiple levels—molecular, cellular, synaptic, and network-wide—to address core mechanisms of neurodegeneration. 'Our goal with this publication is to consolidate the preclinical and clinical findings to explain why rTMS isn't just symptomatic—it is actually disease modifying. This gives us a foundational understanding of how stimulation protocols can directly modulate neurotransmission, reduce inflammation, enhance plasticity, and even promote clearance of toxic proteins,' said Giacomo Koch, MD, PhD, Sinaptica scientific co-founder, Neurologist, Professor of Physiology, University of Ferrara, and Director, Non-Invasive Brain Stimulation Laboratory, Santa Lucia Foundation. The publication reviews the evidence supporting the fundamental mechanisms of action of rTMS treatments in AD. rTMS exerts profound effects from the micro-molecular scale to the macro network-level scale. By engaging distinct pre- and post-synaptic structures within the stimulated neural network, it directly and indirectly influences various cellular and molecular components. These effects work together to stabilize and improve brain function through the following means: Strengthens Neuronal Structures - Upregulates neurotrophic factors e.g. BDNF, leading to neuronal structural changes e.g. via remodeling of dendritic spines. Strengthens Synapses - Modulates neurotransmitter circuits, both through increased production and sensitivity of dopaminergic-, glutamatergic-, and GABA-ergic pathways. Neuroinflammation - Mitigates neuroinflammation by reducing microglial activation and pro-inflammatory cytokines release e.g. by promoting glutamate reuptake. Amyloid - May counteract beta amyloid overproduction and toxic aggregation by interrupting a vicious cycle of hyperexcitability. Tau - Potentially reduces tau hyperphosphorylation and accumulation via the GSK-3β pathway. Clearance - Potentially increases glymphatic clearance of toxic proteins. All of the above mechanisms contribute to restoring network-wide excitation/inhibition imbalance, restoring LTP-like mechanisms of neuroplasticity, and enhancing large-scale connectivity. Authors of this definitive paper are Giacomo Koch (Experimental Neuropsychophysiology Lab, Department of Clinical and Behavioural Neurology, Santa Lucia Foundation IRCCS), Emiliano Santarnecchi (Gordon Center for Medical Imaging, Mass General Research Institute; Harvard Medical School), Harald Hampel (Sorbonne University, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital), Annibale Antonioni (Department of Neuroscience and Rehabilitation, University of Ferrara), and Alessandro Martorana (Memory Clinic, Department of Systems Medicine, University of Tor Vergata). 'Based on this new publication, repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus in the brain's central Default Mode Network is an emerging element of precision medicine in neurology. Based on accumulating basic, translational, and clinical evidence, this standardized targeted non-invasive electro-magnetic brain stimulation will likely be part of the evolving clinical care landscape with different treatments and combinations,' said co-author Dr. Harald Hampel, a leading international brain researcher and Alzheimer's disease (AD) scientist. 'Further clinical studies are warranted to benefit the globally increasing population of AD patients.' As the field moves toward more personalized and mechanistically distinct Alzheimer's therapies, this review provides a vital reference point for researchers, clinicians, and innovators. It supports the integration of rTMS into a precision medicine framework that could transform how providers manage Alzheimer's—potentially shifting the paradigm from reactive care to proactive, highly tailored, connectome-level intervention, including combination therapies. 'We are beginning to see rTMS emerge as a safe, scalable precision medicine platform for Alzheimer's,' said Emiliano Santarnecchi, PhD, co-founder of Sinaptica Therapeutics, Associate Professor of Radiology & Neurology at Harvard Medical School, as well as Director, Precision Neuroscience & Neuromodulation Program and Director, Network Control Laboratory, at Massachusetts General Hospital in Boston, MA. 'This is not just about stimulating the brain—it's about rewiring disease-affected networks with intention and scientific precision.' The publication establishes the translational relevance of these findings, citing Phase 1 and 2 human trials in which targeted, neuronavigated rTMS protocols have boosted memory, stabilized cognitive performance, restored functional brain connectivity, and enhanced gamma rhythm activity—key markers of brain health. These protocols, particularly those focused on the Default Mode Network (DMN), are seen as promising interventions for mild cognitive impairment and Alzheimer's. 'This definitive reference illuminates an evolving paradigm shift away from simplistic linear 'nerve stimulation' toward the new and rapidly progressing field of 'network modulation,' said Ken Mariash, CEO of Sinaptica Therapeutics. 'This publication presents a higher order systems-level approach to how we think about and treat brain diseases. Sinaptica's nDMN therapy induces a cascade of network-wide effects that compound, ultimately restoring the exquisite balance of the networks involved in memory and cognition. In this new context, we can better understand how it was possible to achieve such strong and consistent clinical outcomes in previous Phase 2 trials in mild/moderate Alzheimer's patients. This important publication reinforces everything we're building at Sinaptica by elucidating the neurobiological mechanisms underlying our therapy and validating the importance of targeting the brain's network-level dysfunction with both precision and personalization.' About the SinaptiStim ® System The SinaptiStim ® System is an investigational new approach to treating Alzheimer's disease using non-invasive personalized precision neuromodulation. Calibrated to each individual's brain, the therapy is delivered in weekly 20-minute sessions in a recliner. The SinaptiStim system delivers safe, painless, customized neurostimulation technology targeting the Default Mode Network (DMN), an important brain network associated with episodic memory, introspection, and other cognitive functions. The technology was granted Breakthrough Device Designation by the FDA in 2022. The company is preparing for a pivotal randomized controlled clinical trial in mild-to-moderate Alzheimer's. In this trial, the treatment will be calibrated quarterly using TMS and EEG concurrently in combination with MRI-guided neuronavigation, which enables the SinaptiStim System to achieve customized precise repeatable targeting and safe-yet-effective dosage for each patient, tracking progress and adjusting over time to achieve the best possible individualized outcomes with its nDMN therapy. The pivotal trial will also be designed to determine the effects of SinaptiStim ® System on several biomarkers measuring beta amyloid, phosphorylated tau, neuroinflammation, and synaptic dysfunction. About Sinaptica Therapeutics Sinaptica Therapeutics is a clinical-stage neuromodulation therapeutics company leading the development of a new class of novel personalized therapeutics to revolutionize the treatment of Alzheimer's and other primary neurodegenerative diseases. The company utilizes a patented non-invasive approach to treating Alzheimer's via precision neurostimulation of a key brain network involved in memory, the Default Mode Network. Sinaptica's scientific co-founders pioneered research on this novel approach which a growing body of evidence indicates can slow disease progression. Sinaptica's mission is to bring a safe, effective, and non-invasive neuromodulation therapy to Alzheimer's patients that can help to significantly slow the progression of cognitive, functional, and behavioral decline. Learn more at and follow us on LinkedIn and X @SinapticaTX. The SinaptiStim ® System is for investigational use only. It has not been approved by the U.S. Food and Drug Administration and is not available for commercial sale in any geography.
Business Wire
02-05-2025
- Health
- Business Wire
BREZTRI met primary endpoints in KALOS and LOGOS Phase III trials in asthma
WILMINGTON, Del.--(BUSINESS WIRE)--Positive high-level results from the Phase III KALOS and LOGOS trials in patients with uncontrolled asthma showed that AstraZeneca's fixed-dose triple-combination therapy BREZTRI AEROSPHERE (budesonide/glycopyrronium/formoterol fumarate or BGF (320/28.8/9.6μg)) met all primary endpoints, demonstrating a statistically significant and clinically meaningful improvement in lung function compared with dual-combination inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) medicines. KALOS and LOGOS were replicate, randomized, double-blind trials designed to investigate BREZTRI as a potential treatment for asthma. 1,2 The trials evaluated the efficacy and safety of BREZTRI versus maintenance treatment with ICS/LABA in adults and adolescents with uncontrolled asthma. 1,2 Asthma is a common, chronic respiratory disease characterized by inflammation and muscle tightening in the airway (bronchoconstriction), which can make it difficult to breathe. 3 As many as 262 million people worldwide are affected by asthma, 3 and it is estimated that nearly half of those treated with dual therapy remain uncontrolled, which can significantly limit lung function and decrease quality of life. 4,5 Alberto Papi, Professor and Chair of Respiratory Medicine at the University of Ferrara, and Director of the Respiratory Unit, CardioRespiratory Department, S. Anna University Hospital, Ferrara, Italy, and primary investigator, said: 'Despite advancements in asthma treatments, millions of patients remain uncontrolled, which can cause frequent breathlessness, coughing and wheezing, significantly impacting their ability to perform daily activities. The results from the KALOS and LOGOS trials are exciting and demonstrate the potential of budesonide/glycopyrronium/formoterol to evolve the standard of care to more effectively treat asthma in a single inhaled triple therapy for patients who remain uncontrolled with dual maintenance therapy.' Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: 'We are excited by the positive results from the KALOS and LOGOS trials, which demonstrate that BREZTRI could help improve the lives of the millions of patients living with asthma. These asthma data build on the well-established profile of BREZTRI in COPD, and we look forward to sharing with regulatory authorities to bring this important medicine to a wider group of patients.' There were no new safety or tolerability signals identified for BREZTRI in KALOS or LOGOS. Full results from the two Phase III trials will be shared with regulatory authorities and presented at an upcoming medical meeting. BREZTRI is an inhaled triple-combination therapy approved for the treatment of chronic obstructive pulmonary disease (COPD) in adults in more than 80 countries worldwide including the US, EU, China and Japan. IMPORTANT SAFETY INFORMATION BREZTRI AEROSPHERE ® (budesonide, glycopyrrolate, and formoterol fumarate) Inhalation Aerosol BREZTRI is contraindicated in patients who have a hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or product excipients BREZTRI is not indicated for treatment of asthma. Long-acting beta2-adrenergic agonist (LABA) monotherapy for asthma is associated with an increased risk of asthma-related death. These findings are considered a class effect of LABA monotherapy. When a LABA is used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. Available data do not suggest an increased risk of death with use of LABA in patients with COPD BREZTRI should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition BREZTRI is NOT a rescue inhaler. Do NOT use to relieve acute symptoms; treat with an inhaled short-acting beta2-agonist BREZTRI should not be used more often than recommended; at higher doses than recommended; or in combination with LABA-containing medicines, due to risk of overdose. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs Oropharyngeal candidiasis has occurred in patients treated with orally inhaled drug products containing budesonide. Advise patients to rinse their mouths with water without swallowing after inhalation Lower respiratory tract infections, including pneumonia, have been reported following ICS. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap Due to possible immunosuppression, potential worsening of infections could occur. Use with caution. A more serious or fatal course of chickenpox or measles can occur in susceptible patients Particular care is needed for patients transferred from systemic corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI Hypercorticism and adrenal suppression may occur with regular or very high dosage in susceptible individuals. If such changes occur, consider appropriate therapy Caution should be exercised when considering the coadministration of BREZTRI with long-term ketoconazole and other known strong CYP3A4 Inhibitors. Adverse effects related to increased systemic exposure to budesonide may occur If paradoxical bronchospasm occurs, discontinue BREZTRI immediately and institute alternative therapy Anaphylaxis and other hypersensitivity reactions (eg, angioedema, urticaria or rash) have been reported. Discontinue and consider alternative therapy Use caution in patients with cardiovascular disorders, especially coronary insufficiency, as formoterol fumarate can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles Decreases in bone mineral density have been observed with long-term administration of ICS. Assess initially and periodically thereafter in patients at high risk for decreased bone mineral content Glaucoma and cataracts may occur with long-term use of ICS. Worsening of narrow-angle glaucoma may occur, so use with caution. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI long term. Instruct patients to contact a healthcare provider immediately if symptoms occur Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if symptoms occur Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis or unusually responsive to sympathomimetic amines Be alert to hypokalemia or hyperglycemia Most common adverse reactions in a 52-week trial (incidence ≥ 2%) were upper respiratory tract infection (5.7%), pneumonia (4.6%), back pain (3.1%), oral candidiasis (3.0%), influenza (2.9%), muscle spasms (2.8%), urinary tract infection (2.7%), cough (2.7%), sinusitis (2.6%), and diarrhea (2.1%). In a 24-week trial, adverse reactions (incidence ≥ 2%) were dysphonia (3.3%) and muscle spasms (3.3%) BREZTRI should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors and tricyclic antidepressants, as these may potentiate the effect of formoterol fumarate on the cardiovascular system BREZTRI should be administered with caution to patients being treated with: Strong cytochrome P450 3A4 inhibitors (may cause systemic corticosteroid effects) Adrenergic drugs (may potentiate effects of formoterol fumarate) Xanthine derivatives, steroids, or non-potassium sparing diuretics (may potentiate hypokalemia and/or ECG changes) Beta-blockers (may block bronchodilatory effects of beta-agonists and produce severe bronchospasm) Anticholinergic-containing drugs (may interact additively). Avoid use with BREZTRI Use BREZTRI with caution in patients with hepatic impairment, as budesonide and formoterol fumarate systemic exposure may increase. Patients with severe hepatic disease should be closely monitored INDICATION BREZTRI AEROSPHERE is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). LIMITATIONS OF USE Not indicated for the relief of acute bronchospasm or for the treatment of asthma. Please see full BREZTRI Prescribing Information, including Patient Information. You may report side effects related to AstraZeneca products. Notes Asthma Asthma is a prevalent, chronic respiratory disease affecting as many as 262 million people worldwide, 3 including over 25 million in the US. 6 When uncontrolled, inflammation and muscle tightening in the airway (bronchoconstriction) may cause wheezing, breathlessness, chest tightness, coughing, and even death. 3,7 Many patients remain uncontrolled despite the availability of standard of care medicines and continue to experience significant limitations on lung function and reduced quality of life. 4,5 KALOS and LOGOS Phase III trials KALOS and LOGOS are replicate confirmatory, randomized, double-blind, double-dummy, parallel group, multi-centre, 24-to-52-week variable length Phase III trials to assess the efficacy and safety of BGF (320/28.8/9.6μg and 320/14.4/9.6μg) compared with two fixed-dose, dual-combination therapies of budesonide, an ICS, and formoterol fumarate, a LABA: PT009 (in anAEROSPHERE inhaler) and SYMBICORT pressurized metered-dose inhaler (pMDI). 1,2 KALOS and LOGOS included approximately 4,400 randomized patients. The trial design was optimized to evaluate the 320/28.8/9.6μg dose of BGF. The primary efficacy endpoints for the two individual trials were a change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve 0 to 3 hours (AUC0-3) at Week 24 and trough FEV1 over 12-24 weeks and over 24 weeks. 1,2 In addition to the two registrational trials, KALOS and LOGOS, two qualifying trials, LITHOS and VATHOS, 8,9 also met their primary endpoints. LITHOS and VATHOS included approximately 1,000 randomized patients. AstraZeneca in Respiratory & Immunology Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals is a key disease area and growth driver to the Company. AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit and follow us on social media @AstraZeneca. References Study to Assess PT010 in Adult and Adolescent Participants with Inadequately Controlled Asthma (KALOS) [Online]. Available at: [Last accessed: May 2025]. Study to Assess PT010 in Adult and Adolescent Participants with Inadequately Controlled Asthma (LOGOS) [Online]. Available at: [Last accessed: May 2025]. Global Asthma Network. The Global Asthma Report 2022. [Online]. Available at: [Last accessed: May 2025]. Davis J, et al. Burden of asthma among patients adherent to ICS/LABA: A real-world study. J Asthma. 2019 Mar;56(3):332-340. Buhl R, et al. One-year follow up of asthmatic patients newly initiated on treatment with medium- or high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings. Respir Med. 2020 Feb: 162:105859. U.S. Centers for Disease Control and Prevention (CDC). Most Recent National Asthma Data. [Online]. Available at: [Last accessed: May 2025]. Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372. A 12-week Study to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler Relative to Budesonide Metered Dose Inhaler in Participants with Inadequately Controlled Asthma (LITHOS) [Online]. Available at: [Last Accessed: May 2025]. A 24-Week Efficacy and Safety Study to Assess Budesonide and Formoterol Fumarate Metered Dose Inhaler in Adult and Adolescent Participants with Inadequately Controlled Asthma (VATHOS) [Online]. Available at: [Last Accessed: May 2025]. AstraZeneca Data on File. 2025. REF-270910.
Yahoo
01-04-2025
- Science
- Yahoo
Did Neanderthals migrate as far east as China? Discovery of stone tools suggests it's a possibility
Sign up for CNN's Wonder Theory science newsletter. Explore the universe with news on fascinating discoveries, scientific advancements and more. Stone tools unearthed in southwest China helped a mysterious group eke out a living in a cold and harsh environment 60,000 to 50,000 years ago. But whose hands shaped them? The answer could shake up what's known about human origins during this period of the Stone Age, according to new research. Archaeologists excavating the Longtan site in Yunnan province, on the southwestern edge of the Tibetan Plateau, uncovered hundreds of stone artifacts from two trenches dug into the region's reddish, silty clay. The research team determined many of the tools were crafted in the style known as Quina, which is typically regarded as an archaeological signature of Neanderthals, a species of ancient human. The style, or complex, hasn't been found in East Asia before, the study published Monday in the journal Proceedings of the National Academy of Sciences said. 'The discovery at the Longtan site is remarkable, as it documents this particular tradition far (at least 7,000 or 8,000 kilometers) from the region traditionally associated with this techno-cultural complex,' study coauthor Davide Delpiano, a postdoctoral fellow in Paleolithic archaeology at the University of Ferrara in Italy, said via email. Neanderthals roamed Eurasia for some 400,000 years before disappearing 40,000 years ago, but there is no evidence of their remains east of the Altai Mountains in southern Siberia. Neanderthal bones and skeletons have previously been found alongside Quina stone tools at several sites in Western Europe including at the namesake site of La Quina in southwest France. Quina is one of a number of stone tool styles associated with Neanderthals that archaeologists call Mousterian culture. The unprecedented discovery at Longtan had 'significant implications,' Delpiano said, raising two competing possibilities. Neanderthals could have migrated east and reached what's now China, or a different species of ancient human possibly made stone tools uncannily similar to those being made in Europe during this period known as the Middle Paleolithic. The tool set unearthed at Longtan in 2019 and 2020 include scrapers, used to work hides or wood with one sharp side, stone points that might have been attached to wooden spears, and tools that had notches a bit like a saw. In Europe, Neanderthals used Quina stone tools during a dry and cold period 60,000 to 50,000 years ago in a landscape of open woodland. The tools would have helped Neanderthals hunt migrating herds of reindeer, giant deer, horses and bison, according to the study. Quina tools typically had a long period of use and were often retouched and recycled — suggesting they were a response to patchy resources and a highly mobile lifestyle, the researchers wrote. Analysis of ancient pollen grains from Longtan revealed the climate and environment would have been similar in southwestern China to that of Europe. However, the authors found no animal remains at the site, so it's not known whether the humans who lived there hunted similar animals, they said. 'The Quina package represents an adaptation to highly developed mobility strategies: these artifacts were designed to last a long time, as nomadic human groups were forced to search for resources that, due to increasingly harsh climatic conditions, were becoming scarcer,' Delpiano said. It was possible Neanderthals made it as far east as southwest China, or perhaps they encountered other human species in their home territory, an interaction that allowed their stone tool technology to spread eastward, he said. Fossils from Denisova Cave in the Altai Mountains show Neanderthals lived there about 200,000 years ago at roughly the same time as a sister species known as the Denisovans, who are thought to have lived throughout Asia. The study authors added that skulls found in Xuchang in central China's Henan province also displayed some Neanderthal features, which 'might indicate that human interactions occurred between the West and the East.' 'I would not be surprised if Neanderthals made occasional incursions into Chinese said, the issue is that we currently lack this technological package in the rest of Asia, leaving us without a clear 'breadcrumb trail' to connect in a hypothetical migration path,' Delpiano said. An equally plausible explanation put forward by the study was that the hominins who once called Longtan home — perhaps Denisovans or another unknown species — separately developed the same style of stone tool as Neanderthals in response to the similarly harsh environment. 'While we cannot yet confirm the presence of Neanderthals in China — who were responsible for the Middle Paleolithic (tools) in Europe and Central Asia — we know that their 'sister' species, the Denisovans, were present in the region,' he said.'It is thus tentatively possible to attribute these innovations and ecological adaptations to them,' he said. 'Starting from a base of knowledge — a technological foundation common to European Neanderthals — local groups might have 'reinvented' this tool-making tradition because it was well-suited to their ecological conditions,' Delpiano said. Dongju Zhang, an archaeologist and professor at China's Lanzhou University who wasn't involved in the study, said both hypotheses were plausible, if speculative. More concrete evidence was needed to understand who made the tools, she said. 'To me, it is far too early to give an explanation of the producers of this style in Longtan. I am looking forward to seeing more new finds and more certain human fossil or ancient DNA or paleoproteomic (ancient protein) evidences in East Asia,' she said via email. The only way to prove Neanderthals lived in what's now China is for paleontologists working there to find a Neanderthal fossil in China, said John Shea, a professor of anthropology at Stony Brook University in New York. 'Stone tools are not ID cards,' he said. The new study adds to a body of unresolved questions about how the human story unfolded in Asia before the large-scale arrival of our own species, Homo sapiens, in the region. 'For me, the significance of this paper is that it contributes to an ever-growing list of recent discoveries that highlight Eastern and Southeastern Asia as hotspots for human origins research,' said Ben Utting, a postdoctoral fellow in the department of anthropology at the Smithsonian's National Museum of Natural History in Washington, DC. 'While archaeologists and anthropologists long considered Eastern and Southeastern Asia to be cultural 'backwaters,' these discoveries are helping to reverse that narrative and demonstrate that the humans living in these regions were every bit as behaviorally dynamic and complex as humans living elsewhere at the same time.'
CNN
01-04-2025
- Science
- CNN
Did Neanderthals migrate as far east as China? Discovery of stone tools suggests it's a possibility
Stone tools unearthed in southwest China helped a mysterious group eke out a living in a cold and harsh environment 60,000 to 50,000 years ago. But whose hands shaped them? The answer could shake up what's known about human origins during this period of the Stone Age, according to new research. Archaeologists excavating the Longtan site in Yunnan province, on the southwestern edge of the Tibetan Plateau, uncovered hundreds of stone artifacts from two trenches dug into the region's reddish, silty clay. The research team determined many of the tools were crafted in the style known as Quina, which is typically regarded as an archaeological signature of Neanderthals, a species of ancient human. The style, or complex, hasn't been found in East Asia before, the study published Monday in the journal Proceedings of the National Academy of Sciences said. 'The discovery at the Longtan site is remarkable, as it documents this particular tradition far (at least 7,000 or 8,000 kilometers) from the region traditionally associated with this techno-cultural complex,' study coauthor Davide Delpiano, a postdoctoral fellow in Paleolithic archaeology at the University of Ferrara in Italy, said via email. Neanderthals roamed Eurasia for some 400,000 years before disappearing 40,000 years ago, but there is no evidence of their remains east of the Altai Mountains in southern Siberia. Neanderthal bones and skeletons have previously been found alongside Quina stone tools at several sites in Western Europe including at the namesake site of La Quina in southwest France. Quina is one of a number of stone tool styles associated with Neanderthals that archaeologists call Mousterian culture. The unprecedented discovery at Longtan had 'significant implications,' Delpiano said, raising two competing possibilities. Neanderthals could have migrated east and reached what's now China, or a different species of ancient human possibly made stone tools uncannily similar to those being made in Europe during this period known as the Middle Paleolithic. The tool set unearthed at Longtan in 2019 and 2020 include scrapers, used to work hides or wood with one sharp side, stone points that might have been attached to wooden spears, and tools that had notches a bit like a saw. In Europe, Neanderthals used Quina stone tools during a dry and cold period 60,000 to 50,000 years ago in a landscape of open woodland. The tools would have helped Neanderthals hunt migrating herds of reindeer, giant deer, horses and bison, according to the study. Quina tools typically had a long period of use and were often retouched and recycled — suggesting they were a response to patchy resources and a highly mobile lifestyle, the researchers wrote. Analysis of ancient pollen grains from Longtan revealed the climate and environment would have been similar in southwestern China to that of Europe. However, the authors found no animal remains at the site, so it's not known whether the humans who lived there hunted similar animals, they said. 'The Quina package represents an adaptation to highly developed mobility strategies: these artifacts were designed to last a long time, as nomadic human groups were forced to search for resources that, due to increasingly harsh climatic conditions, were becoming scarcer,' Delpiano said. It was possible Neanderthals made it as far east as southwest China, or perhaps they encountered other human species in their home territory, an interaction that allowed their stone tool technology to spread eastward, he said. Fossils from Denisova Cave in the Altai Mountains show Neanderthals lived there about 200,000 years ago at roughly the same time as a sister species known as the Denisovans, who are thought to have lived throughout Asia. The study authors added that skulls found in Xuchang in central China's Henan province also displayed some Neanderthal features, which 'might indicate that human interactions occurred between the West and the East.' 'I would not be surprised if Neanderthals made occasional incursions into Chinese said, the issue is that we currently lack this technological package in the rest of Asia, leaving us without a clear 'breadcrumb trail' to connect in a hypothetical migration path,' Delpiano said. An equally plausible explanation put forward by the study was that the hominins who once called Longtan home — perhaps Denisovans or another unknown species — separately developed the same style of stone tool as Neanderthals in response to the similarly harsh environment. 'While we cannot yet confirm the presence of Neanderthals in China — who were responsible for the Middle Paleolithic (tools) in Europe and Central Asia — we know that their 'sister' species, the Denisovans, were present in the region,' he said.'It is thus tentatively possible to attribute these innovations and ecological adaptations to them,' he said. 'Starting from a base of knowledge — a technological foundation common to European Neanderthals — local groups might have 'reinvented' this tool-making tradition because it was well-suited to their ecological conditions,' Delpiano said. Dongju Zhang, an archaeologist and professor at China's Lanzhou University who wasn't involved in the study, said both hypotheses were plausible, if speculative. More concrete evidence was needed to understand who made the tools, she said. 'To me, it is far too early to give an explanation of the producers of this style in Longtan. I am looking forward to seeing more new finds and more certain human fossil or ancient DNA or paleoproteomic (ancient protein) evidences in East Asia,' she said via email. The only way to prove Neanderthals lived in what's now China is for paleontologists working there to find a Neanderthal fossil in China, said John Shea, a professor of anthropology at Stony Brook University in New York. 'Stone tools are not ID cards,' he said. The new study adds to a body of unresolved questions about how the human story unfolded in Asia before the large-scale arrival of our own species, Homo sapiens, in the region. 'For me, the significance of this paper is that it contributes to an ever-growing list of recent discoveries that highlight Eastern and Southeastern Asia as hotspots for human origins research,' said Ben Utting, a postdoctoral fellow in the department of anthropology at the Smithsonian's National Museum of Natural History in Washington, DC. 'While archaeologists and anthropologists long considered Eastern and Southeastern Asia to be cultural 'backwaters,' these discoveries are helping to reverse that narrative and demonstrate that the humans living in these regions were every bit as behaviorally dynamic and complex as humans living elsewhere at the same time.'
