ADM

MONDAY, Jan. 6, 2025 -- Palling around with family and friends is more than just fun and relaxing -- it also boosts health. A new study published in the journal Nature Human Behavior says that blood samples show that an active social life appears to boost the immune system and lower risk of illnesses like heart disease, stroke and type 2 diabetes. “These findings drive home the importance of social contact in keeping us well,” Barbara Sahakian , a professor with the University of Cambridge, said in a news release from the college. Researchers identified 175 proteins in blood associated with social isolation and 26 associated with loneliness. Many of these proteins are produced in response to illness -- inflammation, viral infection, immune response, and chronic ailments like heart disease and diabetes, researchers said. “We know that social isolation and loneliness are linked to poorer health, but we’ve never understood why,” lead researcher Chun Shen , a postdoctoral investigator with the University of Cambridge Department of Clinical Neurosciences, said in a news release from the college. “Our work has highlighted a number of proteins that appear to play a key role in this relationship, with levels of some proteins in particular increasing as a direct consequence of loneliness,” Shen continued. For the study, researchers analyzed proteins found in blood samples from more than 42,000 people 40 to 69 donated as part of the long-term UK Biobank health study. The proteins found in the samples were then compared to each person’s self-reported levels of social isolation and loneliness, as well as their overall health. Looking more closely, researchers found five specific proteins that appear in high levels due to loneliness. One of the five, ADM, plays a role in regulating hormones related to stress, as well as the so-called “love hormone” oxytocin. Higher levels of ADM were linked with an increased risk of early death, researchers said. The protein also appeared to play a role in people’s risk of heart disease, dementia and stroke. Elevated ADM is also associated with smaller sizes in key brain regions, researchers said. These regions include the insula, a brain hub for our ability to sense what’s happening in our environment, and the left caudate, which is involved in emotional, reward and social processing. Another protein, ASGR1, is associated with high cholesterol and increased risk of heart disease. “We discovered that both ADM and ASGR1 were strongly associated with a range of biochemical, hematological, and metabolic biomarkers, including CRP (a sign of inflammation), cholesterol, and triglycerides,” researchers wrote in their paper. Other identified proteins play roles in the development of insulin resistance, hardening of the arteries, and cancer progression. "The proteins we’ve identified give us clues to the biology underpinning poor health among people who are socially isolated or lonely, highlighting why social relationships play such an important part in keeping us healthy,” senior researcher Jianfeng Feng , a professor with the University of Warwick, said in a news release. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

MONDAY, Jan. 6, 2025 -- Proteins associated with social isolation and loneliness are implicated in inflammation, antiviral responses, and complement systems, according to a study published online Jan. 3 in Nature Human Behavior . Chun Shen, Ph.D., from the Institute of Science and Technology for Brain-Inspired Intelligence at Fudan University in Shanghai, and colleagues characterized the proteomic signatures of social isolation and loneliness through a proteome-wide association study and protein co-expression network analysis leveraging data from 42,062 participants across 2,920 plasma proteins in the U.K. Biobank. The researchers found that proteins linked to these constructs were involved in inflammation, antiviral responses, and complement systems. During a 14-year follow-up, more than half of these proteins were prospectively linked to cardiovascular disease, type 2 diabetes, stroke, and mortality. Causal relationships were suggested in a Mendelian randomization (MR) analysis from loneliness to five proteins (GFRA1, ADM, FABP4, TNFRSF10A, and ASGR1); colocalization further supported two proteins (ADM and ASGR1). The five MR-identified proteins showed broad associations with other blood biomarkers and with brain volume in regions involved in interoception and emotional and social processes. The relationship between loneliness and cardiovascular diseases, stroke, and mortality was partly mediated by the MR-identified proteins. "This is the first study delineating robust and comprehensive plasma proteomic signatures associated with social isolation and loneliness. The plasma proteome can help bridge the link between social relationships and morbidity and mortality," the authors write. "Comprehending the biology underlying the impact of social relationships on health, particularly the peripheral changes preceding disease, may provide new opportunities for targeted prevention and for effective intervention." Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

With a mortality rate of 20-30% for sepsis and 30-50% for septic shock in developed countries, sepsis represents an enormous public health burden and is responsible for almost 20% of all deaths worldwide Enibarcimab has the potential to become the first treatment addressing the under-lying pathophysiology of sepsis. Combined with precision medicine to identify patients most likely to respond to treatment, this approach is the way towards an effective treatment, after development failures of “one-size-fits-all” therapies AdrenoMed is preparing a confirmatory clinical trial to confirm the reduced septic shock mortality under enibarcimab treatment employing precision medicine In the AdrenOSS-2 Phase II trial, the respective patient subgroup had a statistically significant >60% relative reduction in 28-day mortality vs. placebo HENNIGSDORF, Germany and BERLIN, April 10, 2024 (GLOBE NEWSWIRE) -- Adrenomed AG, the vascular integrity company, today announced that the US Food and Drug Administration (FDA) has granted Fast Track designation to its lead product candidate enibarcimab, a first-in-class non-neutralizing monoclonal antibody, for the treatment of septic shock. AdrenoMed is now preparing a confirmatory Phase IIb/III clinical trial to confirm the reduced septic shock mortality under enibarcimab treatment employing a precision medicine approach. AdrenoMed’s CEO Dr. Richard Jones commented: “We are very pleased that enibarcimab has received Fast Track designation from the FDA, recognizing its potential as an innovative biomarker-guided treatment against septic shock to fill the unmet medical need in this very serious condition with a high death toll. This is a great confirmation of AdrenoMed’s efforts to reduce patient heterogeneity and develop effective treatments by bringing precision medicine also to intensive care units.” Enibarcimab is a non-blocking antibody binding to the vasoprotective hormone adrenomedullin. Applying AdrenoMed’s precision medicine approach, enibarcimab treatment of patients with septic shock resulted in improved organ dysfunction and a relevant reduction of day 28 all-cause mortality from 24% to 8% in the patient population defined by the two biomarkers adrenomedullin and DPP3 in the AdrenOSS-2 trial. With a mortality rate of 20-30% for sepsis1 and 30%-50% for septic shock in developed countries,2 sepsis represents an enormous public health burden and is responsible for almost 20% of all deaths worldwide. Fast Track is a process designed by the FDA to facilitate the development of promising drugs for the treatment of serious conditions that fill an unmet medical need and to accelerate review by the regulatory authority, aimed at getting important new drugs to the patient earlier. A drug that receives Fast Track designation is eligible for more frequent meetings with FDA to discuss development plans for the drug regarding collection of data needed to support its approval; more frequent communication about such things as the design of the proposed clinical trials and use of biomarkers; eligibility for Accelerated Approval and Priority Review, if relevant criteria are met; and Rolling Review. Dr. Stephan Witte, CMO of AdrenoMed, said: “We are very confident that the use of enibarcimab in combination with two biomarkers, Adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3), holds the promise to become the first effective targeted treatment against septic shock. With AdrenoMed’s biomarker-guided approach it is possible to clearly define the patient population benefitting most from enibarcimab, resulting in a more pronounced treatment effect and leading to improved mortality in septic shock.” This was the conclusion also drawn by Prof. Peter Pickkers from the Department of Intensive Care Medicine and Radboud Center for Infectious Diseases (RCI), Nijmegen, Netherlands, in a poster session during the recent ISICEM 2024, which took place in Brussels, Belgium, from March 19 – 22, 2024, where he presented previously unpublished data from a prespecified subgroup of the AdrenOSS-2 trial.3 About AdrenOSS-2 The double-blind, randomized, placebo-controlled, biomarker-guided Phase II trial AdrenOSS-2 (n = 301) had included a prespecified analysis of the role of cDPP3 as a second biomarker (next to ADM) to exclude patients who are unlikely to respond to enibarcimab treatment. DPP3 is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of cDPP3 indicate a high risk of organ dysfunction and mortality. This pathway is mechanistically independent from the loss of vascular integrity, which is known to be the main driver of mortality in septic shock and is indicated by elevated plasma levels of ADM (>70 pg/mL). Consequently, the aim of additional analyses was to investigate the impact of different cDPP3 levels on the treatment effect (28-day all-cause mortality) and to identify a suitable cut-off level. It was shown that the effect of enibarcimab on mortality improves with lower cDPP3 values and that the patients with elevated ADM, but non-elevated baseline cDPP3 (below the upper normal range, ≤ 30-50 ng/mL), benefitted the most from enibarcimab treatment. At 28 days, this patient subgroup had a statistically significant >60% relative reduction in mortality compared to placebo. About AdrenoMed AdrenoMed AG is a German privately financed, clinical-stage biopharmaceutical company. AdrenoMed’s mission is to rescue vascular integrity in order to save the lives of critically ill patients with limited treatment options. Founded in 2009 by a management team with decades of in-depth experience in sepsis and deep knowledge in diagnostics and drug development, the company’s lead product candidate enibarcimab (formerly adrecizumab) is a first-in-class non-blocking monoclonal antibody. Enibarcimab targets the vasoprotective peptide Adrenomedullin, an essential regulator of vascular integrity. Enibarcimab has successfully completed a biomarker-guided, double-blinded, placebo-controlled, randomized, multicenter proof-of-concept Phase II trial with 301 patients suffering from septic shock. For further information, please visit and follow us on LinkedIn and Twitter. Contact AdrenoMed AG Martina Kalle-Brune, Ph.D. phone: +49 (0)3302 207780 bd@adrenomed.com Media Inquiries MC Services AG Eva Bauer / Julia von Hummel phone: +49 (0)89 2102280 adrenomed@mc-services.eu __________________________ 1 Global report on the epidemiology and burden of sepsis: current evidence, identifying gaps and future directions. Geneva: World Health Organization; 2020. . 2 Rudd KE et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the global burden of disease studyThe Lancet 2020;395(10219):200–211. (19)32989-7. 3 Pickkers P, Van Lier D, Knothe C, Struck J, Witte S, Laterre PF, Mebazaa A. Precision medicine in septic shock with enibarcimab – biomarker guided definition of target population, 43rd International Symposium on Intensive Care and Emergency Medicine, Poster A284.