AMRA Medical’s Post

💉 𝗢𝗯𝗲𝘀𝗶𝘁𝘆 𝗨𝗽𝗱𝗮𝘁𝗲! There’s no ignoring the GLP-1 boom, which has acted as a catalyst for this transformative era, redefining the Obesity industry and setting the stage for unprecedented growth. With the market set to skyrocket to $131 billion by 2028, staying ahead of the curve is essential for leaders in this space. The 𝗜𝗻𝗻𝗼𝘃𝗮𝘁𝗶𝗼𝗻 𝗶𝗻 𝗢𝗯𝗲𝘀𝗶𝘁𝘆 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰𝘀 𝗦𝘂𝗺𝗺𝗶𝘁 – 𝗪𝗲𝘀𝘁 𝗖𝗼𝗮𝘀𝘁 makes its breaking debut to San Diego this December, as the only industry focused event dedicated solely to innovative obesity drug development, from discovery to early clinical development. Explore what's in store here: https://ter.li/ozlfk2 A sneak peak of what’s to expect: ◽𝗢𝗽𝘁𝗶𝗺𝗶𝘇𝗲 𝗕𝗼𝗱𝘆 𝗖𝗼𝗺𝗽𝗼𝘀𝗶𝘁𝗶𝗼𝗻 𝗔𝗽𝗽𝗿𝗼𝗮𝗰𝗵𝗲𝘀: Uncover innovative therapies that prioritize fat loss while preserving muscle, ensuring healthier, long-term weight management ◽𝗗𝘂𝗿𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗦𝘁𝗿𝗮𝘁𝗲𝗴𝗶𝗲𝘀 𝗳𝗼𝗿 𝗦𝘂𝘀𝘁𝗮𝗶𝗻𝗲𝗱 𝗢𝘂𝘁𝗰𝗼𝗺𝗲𝘀: Explore ground-breaking methods aimed at delivering long-term, lasting results to maintain weight loss and prevent regain, including combination therapies, gene editing, and more ◽𝗣𝗶𝗼𝗻𝗲𝗲𝗿𝗶𝗻𝗴 𝗥𝗲𝘀𝗲𝗮𝗿𝗰𝗵 𝗕𝗲𝘆𝗼𝗻𝗱 𝗚𝗟𝗣-𝟭: Stay ahead with the latest on novel drug classes and targets such as Amylin, CB1, and the latest insights into mitochondrial biology and adipose tissue, offering fresh avenues for effective obesity treatments ◽𝗣𝗮𝘁𝗶𝗲𝗻𝘁-𝗖𝗲𝗻𝘁𝗿𝗶𝗰 𝗗𝗿𝘂𝗴 𝗗𝗲𝘃𝗲𝗹𝗼𝗽𝗺𝗲𝗻𝘁: Explore oral GLP-1 agonists and innovative administration routes that promise improved patient adherence and outcomes View the full list of topics covered here: https://ter.li/ozlfk2 🔉 Get ready to hear from: Adam Mendelsohn, Anton Pekcec, Christel Menet, David Bearss, David Tingley, Ethan Weiss, Feng Liu, Harith Rajagopalan, James Peyer,, Karen Wurster, Micah T. Webster,, Mark Fineman, Mark Sleeman, Martijn van de Bunt, Olivia Osborn, Punit Dhillon, Roman V. Dvorak,, Ruchi Gupta, Samuel Klein, 𝗧𝗶𝗺𝗼𝘁𝗵𝘆 𝗞𝗲𝗶𝗳𝗳𝗲𝗿 This December, join your industry and benchmark your development and align your 2025 R&D strategies with the latest industry trends to stay ahead of the curve and ensure your place in the future of obesity therapeutics.

Cool paper in Cell Metabolism: A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 https://lnkd.in/eAx-DmSk The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivoabolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer.

Unveiling the Cellular Mechanism of Fasting: Implications for Metabolic Health and Cancer Treatment Fasting has long been recognized for its health benefits, but recent findings provide insight into the cellular mechanisms behind these effects. During fasting, liver cells reduce overall protein synthesis, yet a critical protein, eIF4E, becomes phosphorylated (P-eIF4E), a key step in breaking down fats into ketone bodies. This process is initiated by increased fatty acids during fasting, which activate AMPK and MNK proteins, ultimately leading to the activation of P-eIF4E. Significantly, certain cancers, such as pancreatic cancer, can exploit ketone bodies as an energy source. A study demonstrated that blocking P-eIF4E with the drug eFT508 slows the growth of pancreatic tumors in mice on a ketogenic diet. This suggests that combining eIF4E inhibitors with a ketogenic diet could offer a novel approach to treating pancreatic cancer, a notoriously challenging malignancy. #Fasting #CellularMetabolism #CancerResearch #KetogenicDiet #PancreaticCancer #Metabolism #AMPK #eIF4E

Study: Lilly pill reduces heart attacks and other adverse cardiovascular events by nearly 86% In a mid-stage trial, Eli Lilly's experimental pill muvalaplin significantly reduced levels of lipoprotein(a) or Lp(a), a form of inherited high cholesterol, according to Reuters. https://lnkd.in/ebMDkbcc. Presented at the American Heart Association meeting in Chicago, the highest dose of muvalaplin lowered Lp(a) levels by 70% using a traditional blood test and by nearly 86% with a more specific test developed by the company. Ruth Gimeno, Lilly's group vice president for diabetes and metabolic research, stated that the company is considering the next steps for advancing to late-stage trials. Muvalaplin stands out as the only oral treatment among several injectable therapies being tested for high Lp(a), a risk factor for heart disease affecting one in five people globally. Unlike LDL cholesterol, which can be managed with diet and statins, there are no approved treatments for Lp(a), and few people are aware they have it. Elevated Lp(a) levels can significantly increase the risk of heart attacks, strokes, aortic valve narrowing, and peripheral artery disease. Individuals of African and South Asian ancestry are at the highest risk. The trial included 233 adults with high Lp(a) levels, comparing three daily doses of muvalaplin (10, 60, and 240 milligrams) with a placebo. Researchers measured Lp(a) levels using both traditional blood tests and a new method that assesses intact Lp(a) particles in the blood. "We'll have to have discussions with regulators, but we're very excited," Gimeno said in an interview, noting that large trials are needed to prove that lowering Lp(a) actually reduces heart attacks and other adverse cardiovascular events. At the same meeting, London-based Silence Therapeutics shared the 60-week results of a Phase 2 trial involving 180 patients for their drug zerlasiran. Zerlasiran operates by reducing the activity of the LPA gene, which is responsible for high levels of Lp(a), using a technology called short interfering RNA (siRNA). Picture credit: lanereport #cholesterol #heart #strokes #rna #lilly #heartattacks #healthcare #lpa #lipoprotein

Study: Lilly pill reduces heart attacks and other adverse cardiovascular events by nearly 86% In a mid-stage trial, Eli Lilly's experimental pill muvalaplin significantly reduced levels of lipoprotein(a) or Lp(a), a form of inherited high cholesterol, according to Reuters. https://lnkd.in/ewm-dvit Presented at the American Heart Association meeting in Chicago, the highest dose of muvalaplin lowered Lp(a) levels by 70% using a traditional blood test and by nearly 86% with a more specific test developed by the company. Ruth Gimeno, Lilly's group vice president for diabetes and metabolic research, stated that the company is considering the next steps for advancing to late-stage trials. Muvalaplin stands out as the only oral treatment among several injectable therapies being tested for high Lp(a), a risk factor for heart disease affecting one in five people globally. Unlike LDL cholesterol, which can be managed with diet and statins, there are no approved treatments for Lp(a), and few people are aware they have it. Elevated Lp(a) levels can significantly increase the risk of heart attacks, strokes, aortic valve narrowing, and peripheral artery disease. Individuals of African and South Asian ancestry are at the highest risk. The trial included 233 adults with high Lp(a) levels, comparing three daily doses of muvalaplin (10, 60, and 240 milligrams) with a placebo. Researchers measured Lp(a) levels using both traditional blood tests and a new method that assesses intact Lp(a) particles in the blood. "We'll have to have discussions with regulators, but we're very excited," Gimeno said in an interview, noting that large trials are needed to prove that lowering Lp(a) actually reduces heart attacks and other adverse cardiovascular events. At the same meeting, London-based Silence Therapeutics shared the 60-week results of a Phase 2 trial involving 180 patients for their drug zerlasiran. Zerlasiran operates by reducing the activity of the LPA gene, which is responsible for high levels of Lp(a), using a technology called short interfering RNA (siRNA). Picture credit: lanereport #cholesterol #heart #strokes #rna #lilly #heartattacks #healthcare #lpa #lipoprotein

🗞️ This week's Metabolic News Weekly emphasizes the overlap of type 2 diabetes (#T2D) and metabolic dysfunction-associated steatotic liver disease (#MASLD), highlighting their shared risk factors and the efficacy of certain treatments. Key Insights: ⏵ #Obesity and insulin resistance are common risk factors for type 2 diabetes and MASLD. ⏵ #Retatrutide, a triple hormone receptor agonist, significantly reduces liver fat. ⏵ #Tirzepatide improves MASH resolution and fibrosis, promoting weight loss. ⏵ The dual #GLP-1 and glucagon receptor agonist, #survodutide, shows promising results in treating fatty liver disease. ⏵ The collaborative efforts of Boehringer Ingelheim and Zealand Pharma are enhancing GLP-1/glucagon receptor dual agonist therapies. Impact: ⏵ New therapies could significantly improve quality of life and treatment outcomes for patients with MASLD. ⏵ Enhancing understanding of metabolic diseases through shared risk factor management. ⏵ Potential shifts in therapeutic strategies for treating metabolic dysfunction. ⏵ Reduced healthcare costs through effective management of diabetes and liver disease. ⏵ Increased emphasis on personalized medicine in managing metabolic health. Check out the full edition here for this weeks news and more👇

The role of 𝗚𝗔𝗕𝗔 𝗶𝘀 𝗸𝗲𝘆 to understanding 𝗧𝘆𝗽𝗲 𝟭 𝗗𝗶𝗮𝗯𝗲𝘁𝗲𝘀 𝗱𝘆𝘀𝗳𝘂𝗻𝗰𝘁𝗶𝗼𝗻𝘀 in the pancreas. β-cells are the primary source of GABA in the endocrine system. GABA is a crucial neurotransmitter responsible for communication between the α and β endocrine cells in the islets. This is essential for the 𝗽𝗿𝗼𝗽𝗲𝗿 𝘀𝗲𝗰𝗿𝗲𝘁𝗶𝗼𝗻 𝗼𝗳 𝗴𝗹𝘂𝗰𝗮𝗴𝗼𝗻 from the α-cells and 𝗶𝗻𝘀𝘂𝗹𝗶𝗻 from the β-cells in response to glucose intake. Our search for a functional cure led us to the work published in 𝗡𝗮𝘁𝘂𝗿𝗲 𝗠𝗲𝘁𝗮𝗯𝗼𝗹𝗶𝘀𝗺 by our scientific advisor, Dr. Walker Hagan  (https://lnkd.in/dgDJ_vJx). He discovered that GABA is depleted in type 1 diabetic islets devoid of functional  β-cells and in the islets with residual β-cells that are still producing insulin. This discovery is of considerable significance, as it implies that all T1D patients, including those who maintain partial insulin secretion, are devoid of GABA in the pancreas. Administering exogenous GABA would be expected to correct the intra-islet GABA deficiency in T1D patients, thereby restoring normal β and α-cell functions. Additionally, GABA elevates other hormones critical for the regeneration of β-cell mass, such as GLP-1 and Gastrin, and stimulates  β-cell proliferation. Furthermore, GABA is an important inhibitor of the autoimmunity response for β-cell destruction in T1D. #Levicure #Breaktrough #T1D #Type1Diabetes #GABA Nature Magazine

Delighted to share that my latest research article, "Effects of purslane on liver function tests, metabolic profile, oxidative stress and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: a randomized, double-blind clinical trial", has been published! This study investigates the potential therapeutic effects of Portulaca oleracea, also known as purslane, on liver function and metabolic health in patients with non-alcoholic fatty liver disease. Our findings suggest that purslane supplementation may have a positive impact on liver function tests, metabolic profile, and oxidative stress levels in these patients. Read the full article to learn more about the study's results, and implications for the management of NAFLD. https://lnkd.in/dPzyW82d #NonAlcoholicFattyLiverDisease #Purslane #LiverHealth #NutritionResearch #ClinicalTrial

Swiss obesity start up SixPeaks Bio AG has made a good start, announcing a US$30m Series A financing led by Versant Ventures and a US$80m biobucks partnership with AstraZeneca plc. SixPeaks Bio, launched with US$30m in Series A funding led by Versant Ventures, which is known for its build to buy strategy, and announced a two-year collaboration with AstraZeneca to co-develop its dual-specific antibody that targets the activin type IIA and B receptors, which blocks myostatin signalling. Disruption of myostatin signaling increases muscle mass and decreases glucose levels, a potential way to treat obesity. Treatments for the complex syndrome are projected to create a US$100bn market by 2030. The British drugmaker like Roche aims to come from behind in the heated obesity market opportunity. SixPeaks Bio is focussed on preserving muscle mass, which could be a good complementation for GLP-1 receptor agonists such as semaglutide or tirzepatide that have made Eli Lilly and Novo Nordisk to No. 1 and No. 2 global pharma companies in terms of market calitalisation due to the diabetes/obesity drug’s ability to decrease blood glucose levels and body mass index by centrally regulating hunger. SixPeaks assumes its drug to be effective as monotherapy or in combination with GLP-1 receptor agonistic incretins. The company is also developing a preclinical conjugate combining both incretins and Myosin signalling blockers. After having terminated two GLP1 receptor agonist programmes last year, AstraZeneca has already licenced an oral Phase I candidate from Chineses Eccogene Co. Ltd. The dual acting programme named AZD6234 is an amylin and calcitonon receptor agonist. Calcitonin promotes insulin sensitivity, and can inhibit gastric emptying, the thyroid hormone promotes gallbladder relaxation, increases energy expenditure and induces satiety as well as weight loss. Amylin, derived from pancreatic beta cells, regulates plasma glucose by delaying gastric emptying after meal ingestion, and modulates glucagon secretion and central satiety signalling in the brain.

Diet intervention (ketogenic diet and intermittent fasting) combined with a P-eIF4E inhibitor to reduce pancreatic cancer growth showed in this preclinical study. Check out this new interesting paper!