miR-132

Researchers have analyzed how an antidiabetic treatment could help control the growth of tumors, potentially paving the way for the design of better cancer treatments. Flinders University researchers have analysed how an antidiabetic treatment could help control the growth of tumours, potentially paving the way for the design of better cancer treatments. The new study investigated what happens when metformin, a type 2 diabetes medication, is used to treat colorectal cancer cells, in the process demonstrating that it could be exploited to develop new cancer therapies. Previous epidemiology studies show that taking metformin helps protect diabetes patients from developing some forms of cancer including bowel, or colorectal, cancer. The Flinders' researchers sought to understand how taking metformin medication impacts cancer cells and how this could help with future cancer treatments. "Using the latest techniques, we analysed how metformin helps to stop colorectal cancer cells from growing and multiplying by controlling certain 'pathways' inside the cells that help to regulate growth and division," says lead author Dr Ayla Orang from Flinders University's College of Medicine and Public Health. "Importantly, our work has pinpointed that metformin uses small pieces of RNA (called microRNAs) to act as a 'circuit breaker' and turn off certain genes that are involved in cell growth and division, so it is possible that our findings could eventually be used to develop a new targeted cancer therapy. "In particular, we found that metformin increases the levels of certain microRNAs, like miR-2110 and miR-132-3p, which then target specific genes and slow down the growth and progression of tumours. "With this information we may be able to develop RNA-based therapies -- new treatments for cancer that target RNA molecules (like microRNAs)," she says. The research, Restricting Colorectal Cancer Cell Metabolism with Metformin: An Integrated Transcriptomics Study, used advanced techniques to study microRNAs, and the entire set of genes being expressed in the colon cancer cells, to help understand how metformin affects the cells. Metformin increased the levels of certain microRNAs (miR-2110 and miR-132-3p) that target a specific gene (PIK3R3). This process helps to slow down the growth of cancer cells and stop them from multiplying too quickly. Another gene (STMN1) was also targeted by different microRNAs, which led to slower cell growth and a delayed cell cycle. Senior authors of the study, Associate Professor Michael Michael and Professor Janni Petersen say the results are a step forward in our understanding of the way metformin disrupts cancer cell growth and how they could be used to fight cancer. "Our research provides new insights into the molecular mechanisms of how metformin works, and how we might be able to target genes responsible for turning normal cells cancerous," says Associate Professor Michael. "This is important because it shows the potential of metformin as a preventive agent for reducing the growth of cancer in the bowel, and the emergence of RNA therapeutics as a promising new avenue for exploring the clinical efficacy of these findings. "We need to further investigate the potential therapeutic benefits of targeting specific miRNAs or pathways using RNA-based therapies for the treatment of cancer. Having used metformin to unravel metabolism in cancer cells, the next stage of research is focusing on specific cell pathways, which should lead to animal studies and then human clinical trials."

25 March, 2024 – Novo Nordisk and Cardior Pharmaceuticals today announced that Novo Nordisk has agreed to acquire Cardior for up to 1.025 billion Euros, including an upfront payment and additional payments if certain development and commercial milestones are achieved. Cardior is a leader in the discovery and development of therapies that target RNA as a means to prevent, repair and reverse diseases of the heart. The company’s therapeutic approach targets distinctive non-coding RNAs as a platform for addressing root causes of cardiac dysfunctions with an aim to achieve lasting patient impact. The agreement includes Cardior’s lead compound CDR132L, currently in phase 2 clinical development for the treatment of heart failure. The acquisition is an important step forward in Novo Nordisk’s strategy to establish a presence in cardiovascular disease. Novo Nordisk aims to build a focused, impactful portfolio of therapies through internal and external innovation to address the significant unmet needs that still exist within cardiovascular disease, the most common cause of death globally. “By welcoming Cardior as a part of Novo Nordisk, we will strengthen our pipeline of projects in cardiovascular disease where we already have ongoing programmes across all phases of clinical development,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “We have been impressed by the scientific work carried out by the Cardior team, especially on CDR132L, which has a distinctive mode of action and potential to become a first-in-class therapy designed to halt or partially reverse the course of disease for people living with heart failure.” CDR132L is designed to halt and partially reverse cellular pathology by selectively blocking abnormal levels of the microRNA molecule miR-132, potentially leading to long-lasting improvement in heart function. In a phase 1b trial published in the European Heart Journal1, CDR132L was reported to be safe and well tolerated and the results suggested cardiac functional improvements in people with heart failure compared to placebo. CDR132L is currently being investigated in the phase 2 trial HF-REVERT in 280 people with heart failure with reduced ejection fraction (HFrEF) who have previously suffered a heart attack (myocardial infarction). The first patient was dosed in the HF-REVERT trial in July 2022. Novo Nordisk plans to initiate a second phase 2 trial that will investigate CDR132L in a chronic heart failure population with cardiac hypertrophy – a condition that causes the walls of the heart muscle to become thick and stiff, affecting the heart’s ability to pump blood. “This acquisition is a reflection of CDR132L’s transformative potential as a disease-modifying therapy for heart failure,” said Claudia Ulbrich, MD, CEO and co-founder of Cardior. “Novo Nordisk is the ideal partner based on its deep clinical and commercial expertise combined with its resources to accelerate our late-stage development programme, including through larger registrational studies. We look forward to advancing CDR132L towards market approval.” The closing of the acquisition is subject to receipt of applicable regulatory approvals and other customary conditions and is expected to happen in the second quarter of 2024. The transaction will not impact Novo Nordisk’s previously communicated operating profit outlook for 2024 or the ongoing share buy-back programme. Novo Nordisk will fund the acquisition from financial reserves. Heart failure is a chronic, progressive condition in which the heart muscle is unable to pump enough blood to meet the body’s needs for blood and oxygen. The condition leads to frequent hospitalisations, and more than half of people diagnosed with heart failure die within five years2. Heart failure affects more than 65 million people globally and is most commonly caused by heart conditions such as ischaemic heart disease, cardiomyopathy or high blood pressure3. The condition cannot be cured. Current therapies can slow but not halt disease progression4, and morbidity and mortality remain high5. Cardior works to identify and counteract the molecular mechanisms of the broad area of ischaemic-induced heart failure as well as specific cardiac diseases such as hypertrophic and dilated cardiomyopathies. Cardior primarily seeks to advance a novel class of antisense oligonucleotides (ASOs) targeting so-called non-coding RNAs (ncRNAs) that are able to act on several key disease pathways simultaneously, triggering a concerted therapeutic effect against key hallmarks of heart disease, including cardiac hypertrophy, fibrosis, impaired contractility and reduced vascularization. Although ncRNAs are not translated into proteins, they are important for the regulation of critical cellular processes and their dysregulation is a hallmark of many diseases. With its deep knowledge in RNA biology, Cardior is developing a clinically-oriented approach to restore normal levels and functions of these key players in the pathological processes of cardiac diseases. Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 63,400 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com, Facebook, Instagram, X, LinkedIn and YouTube. Cardior Pharmaceuticals is a leading clinical-stage biopharmaceutical company pioneering the discovery and development of RNA-based therapeutics designed to prevent, repair and reverse diseases of the heart. Cardior’s therapeutic approach uses distinctive non-coding RNAs as an innovative platform for addressing the root causes of cardiac dysfunctions. The company aspires to bring transformative therapeutics and diagnostics to patients and thereby make a lasting impact on the treatment of cardiac diseases worldwide. 1 Täubel J et al. European Heart Journal 2021 Jan 7;42(2):178-188 Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study - PubMed (nih.gov) 2 Jones NR et al. European Journal of Heart Failure 2019 Nov; 21(11): 1306–1325 Survival of patients with chronic heart failure in the community: a systematic review and meta‐analysis - PMC (nih.gov) 3 Bragazzi NL et al. Preventive Cardiology 2021;28(15):1682-1690 Burden of heart failure and underlying causes in 195 countries and territories from 1990 to 2017 – PubMed (nih.gov) 4 McDonagh TA et al. European Heart Journal 2021 Sep 21;42(36):3599-3726 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure - PubMed (nih.gov) 5 Savarese G, Lund LH. Cardiac Failure Review. 2017;03(01):7-11 Global Public Health Burden of Heart Failure - PubMed (nih.gov) The content above comes from the network. if any infringement, please contact us to modify.

Novo Nordisk is adding on to its cardiovascular drug pipeline with the acquisition of Cardior Pharmaceuticals, a genetic medicines developer whose lead program is in mid-stage clinical testing in heart failure. The Danish pharmaceutical giant said Monday that it has committed up to €1.025 billion (about $1.1 billion) to acquire Cardior. Novo Nordisk did not provide a financial breakdown of the deal, other than to say that the sum includes an upfront payment as well as development and commercial milestones that were not specified. Hanover, Germany-based Cardior discovers and develops genetic medicines intended to prevent, repair, and even reverse diseases of the heart. Its drugs are antisense oligonucleotides, a class of medicines that employ small pieces of DNA or RNA to stop production of a disease-causing protein. Cardior’s RNA medicines specifically target non-coding RNA. While this type of RNA does not encode a protein, it does regulate certain cellular processes. Cardio says that by targeting non-coding RNAs, its antisense oligonucleotides can act on several disease pathways, which in turn offers a therapeutic effect in heart diseases. Lead Cardior program CDR132L is designed to block a microRNA molecule called miR-132. This non-coding RNA has been studied for its role in neuronal cells, inflammation, and cancer. Cardior’s focus is on the role that excessive miR-132 activity has on the heart. The drug candidate is designed to selectively block abnormal levels of miR-132, which could in turn halt and partially reverse the effects of heart failure, a condition affecting the heart muscle’s ability to pump blood to the rest of the body. While current treatment options address heart failure symptoms, Cardior claims its drug address an underlying cause of the disorder. In a 28-patient Phase 1b study, results showed Cardior’s intravenously infused CDR132L was safe and well tolerated. Additionally, results from this placebo-controlled, dose-escalating study showed improvement in cardiac function. The results were published in 2021 in the European Heart Journal. After reporting those data, Cardior went on to raise a €64 million (about $69.3 million) Series B round of financing to continue clinical development of CDR132L, which is currently in Phase 2 testing in heart failure. This drug is also in preclinical development for two additional indications: heart failure with preserved ejection fraction and dilated cardiomyopathy. Two other Cardior programs are in preclinical development for hypertrophic cardiomyopathy. While Novo Nordisk’s metabolic disorder drugs continue to drive record sales, the company has said its growth strategy includes expanding into adjacent areas, such as cardiovascular conditions. In 2021, Novo Nordisk paid $100 million up front to acquire global rights to a Prothena drug in development for the cardiomyopathy caused by the rare disease hereditary transthyretin amyloidosis. That antibody drug is currently in Phase 2 testing under Prothena. Last fall, Novo Nordisk paid $60 million up front for three preclinical cardiovascular drugs from Valo Health. The pharma giant characterizes the Cardior acquisition as “an important step forward in Novo Nordisk’s strategy to establish a presence in cardiovascular disease.” “We have been impressed by the scientific work carried out by the Cardior team, especially on CDR132L, which has a distinctive mode of action and potential to become a first-in-class therapy designed to halt or partially reverse the course of disease for people living with heart failure,” Martin Holst Lange, executive vice president for development at Novo Nordisk said in a prepared statement. Image: Magicmine, Getty Images