netrin-1

NEW YORK, June 17, 2024 /PRNewswire/ -- Kathryn J. Moore, PhD, the Jean and David Blechman Professor of Cardiology in the Department of Medicine at NYU Grossman School of Medicine, has been awarded the Lefoulon Delalande Institut de France Grand Prize in Science (the Grand Prix Scientifique) for 2024. Moore, also director of the Cardiovascular Research Center at NYU Langone Health, was honored for her answers to central questions in the field of cardiovascular physiology, including, for instance, how persistent activation of the immune system (chronic inflammation) by excess cholesterol drives the development of plaques in the arteries of patients with atherosclerosis. The award is conferred annually by the Lefoulon-Delalande Foundation at the Institut de France in various areas of medical science. With a different theme each year (but often focused on cardiology), the prize comes with a $650,000 award, making it the largest of its kind in cardiovascular research. Moore's research team discovered that the immune system recognizes certain (oxidized) forms of cholesterol using signaling proteins (receptors) designed to detect foreign invaders (e.g. bacteria). This immune response sets off chronic inflammation of the arteries that results in the formation of plaques, which compromise arterial blood flow and can lead to heart attacks. Moore and colleagues also showed that when immune system cells known as macrophages engulf oxidized cholesterol, it can lead to the formation of cholesterol crystals that sound an inflammatory alarm. These intracellular cholesterol crystals trigger a protein group called the NLRP3-inflammasome complex. This complex is responsible for generating the potent pro-inflammatory cytokine interleukin-1b, whose inhibition has been shown in clinical trials to reduce risk of cardiovascular events. "I am thrilled to receive this prize that honors the work carried out by my research team over the last two decades," said Moore. "It has been an honor to work with such talented trainees and world-class colleagues in pursuit of answers to why chronic inflammation develops in response to hyper-cholesterolemia and drives cardiovascular diseases that place such a burden on millions of patients globally." In other work, Moore and colleagues revealed the role of a molecule called netrin-1 in causing macrophages to accumulate in atherosclerotic plaques and fat (adipose) tissue of obese individuals to drive a vicious cycle of chronic inflammation, insulin resistance, and cardiometabolic disease. Moore also made discoveries on the role of tiny RNA molecules in regulating the pathways that control cholesterol levels in cells and the blood. She showed that these "microRNAs" can repress the pathways that help cells rid themselves of excess cholesterol, resulting in the accumulation of cholesterol-laden immune cells in plaques and the development of atherosclerotic disease. Importantly, she found that microRNAs, in particular miR-33, could be targeted therapeutically to promote the normal balance of cholesterol in the body. "The impact of Dr. Moore's work on both the current and near-future of treatment for cardiovascular diseases is nothing short of profound," said Glenn I. Fishman, MD, director of the Leon H. Charney Division of Cardiology at NYU Grossman School of Medicine. "It is great to see such an innovative and dedicated scientist be recognized in this way," added Fishman, also vice chair for research for the Department of Medicine. "There is no better example than Dr. Moore of the kind of exemplary scientist we seek to support at our institution," said Dafna Bar-Sagi, PhD, senior vice president, vice dean for science, and chief scientific officer at NYU Langone Health. "Congratulations to her and the entire cardiology team." Dr. Moore shares the award this year with Christopher Glass, MD, PhD, professor of Cellular and Molecular Medicine at the University of California at San Diego. Previous awards recognizing Dr. Moore's research include in 2022 a Gill Heart and Vascular Institute Award, given each year to honor individuals who have made outstanding contributions to the field of cardiovascular medicine. In 2021, she was elected to the National Academy of Sciences, among the highest honors in the scientific field. Members of the academy serve pro bono as "advisers to the nation" on science, engineering, and medicine. Lastly, in 2017, Dr. Moore received a $6.7 million "Outstanding Investigator Award" from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. The award funded her work seeking to determine the role of an unusual form of genetic material called long noncoding RNA, or lncRNA. She found that this class of molecules regulates the body's immune response to plaques, which are made of cholesterol, fatty substances, and cellular waste that blocks arteries. Understanding IncRNAs may lead to new treatment approaches for cardiovascular diseases that remain the leading cause of death worldwide, she says. Contact: Gregory Williams, [email protected] SOURCE NYU Langone Health System

A new scientific finding is the foundation for the first clinical trial in the U.S. to study an experimental drug's ability to fight pancreatic cancer with metastasis to the liver.   Pancreatic cancer is tricky to manage because it spreads easily and early, and the tumors have a unique biological makeup. But, researchers made a breakthrough by learning about the genetic changes that occur during tumor migration -- and also found a drug that can obstruct the process. The next step is a groundbreaking clinical trial at the University of Rochester's Wilmot Cancer Institute, planned for early in 2024, to test the drug from their laboratory discovery, said senior investigator Darren Carpizo, MD, PhD, co-leader of Wilmot's Genetics, Epigenetics and Metabolism research program, and chief of Surgical Oncology at the University of Rochester Medical Center. "We will be the first institution in the U.S. to study the safety and effectiveness of the experimental drug, known as NP137, on pancreatic cancer that has spread to the liver," Carpizo said. Carpizo and several collaborators recently published the results of their bench science investigation in the journal Cell Reports, and Carpizo will lead the Wilmot clinical trial with Aram Hezel, MD, chief of Hematology/Oncology at Wilmot, and Nabeel Badri, MBChB, a medical oncologist at Wilmot. The five-year survival rate for pancreatic cancer is only 12 percent, which is a slight increase in 2023 compared to previous years. The number of cases is rising worldwide, however, and by 2030, pancreatic cancer is predicted to be the second leading cause of cancer deaths. Why is pancreatic cancer deadly? First, because it spreads (metastasizes) very early during its development. In 85 percent of patients, the cancer has already spread outside of the pancreas at diagnosis. Even when the cancer is localized to the pancreas and surgical removal is possible, the majority of patients face a recurrence of their cancer. The metastasis causes these patients to eventually succumb to the disease, which is why researchers are focused on understanding the biology of metastatic pancreatic cancer. Second, although pancreatic cancer cells do not have to travel far to reach the liver, along the way they genetically reprogram themselves and become stronger. The result: newly seeded cancer cells in the liver have a distinctly different biology from the primary tumor in the pancreas, and are able to resist standard treatment, Carpizo said. In their latest work, Wilmot researchers built on what was already known about a key gene, Netrin-1, involved in pancreas, breast and colon cancers. They discovered, for the first time, the complex mechanisms that allow Netrin-1 to drive the lethal, genetic changes as pancreatic cancer cells migrate to the liver. They also showed how Netrin-1 activates hepatic stellate cells, which are involved in liver fibrosis, a serious chronic disease, priming the liver as a host for cancer. In mice and in tissue studies, when researchers suppressed Netrin-1 with the anti-cancer drug (NP137), cancer was less likely to spread and cancer cell death occurred. The team includes scientists from Rutgers University, where Carpizo worked as a surgeon-scientist before joining Wilmot in 2020, Fox Chase Cancer Center in Philadelphia, and a laboratory in France. The Wilmot clinical trial will likely require eligible patients to take two cycles of NP137 before surgery, undergo surgery to remove the cancer, and then take more of the experimental medication along with chemotherapy after surgery for up to six months, Carpizo said. He noted that NP137 is made by Netris Pharma, of Lyon, France, and is currently being tested in clinical trials in that country. The Pancreatic Cancer Action Network (PanCAN) funded much of the work through a grant to Carpizo; Wilmot also provided pilot funding. PanCAN has emphasized that the recent, small uptick in survivorship rates for pancreatic cancer is due to transformative research and clinical trials, and strongly recommends that patients talk to their oncologists about clinical trials at every stage of their disease. Carpizo's study is part of a larger collaborative effort at Wilmot aimed at pancreatic cancer. Others, including URMC Surgery Chair David Linehan, MD., and Wilmot investigator Scott Gerber, PhD., and members of the Cancer Microenvironment research program, are also conducting studies on new, targeted treatments. The goal is to use newly discovered drugs in combination with immunotherapy, radiation therapy, and chemotherapy to attack pancreatic cancer.

ImmunoNET Study Aims to Expand Patient Response to Immunotherapies LYON, France--(BUSINESS WIRE)-- NETRIS Pharma, a clinical-stage private biopharmaceutical company developing a new class of drugs based on dependence receptor biology, today announced dosing of the first patient in the ImmunoNET trial. ImmunoNET is a multicenter, open-label, proof of concept phase II trial designed to assess the clinical and biological activity of NETRIS Pharma’s first drug candidate, NP137, as add-on therapy in patients with advanced/metastatic solid tumors treated by standard immunotherapies. “The enrollment of the first patient in ImmunoNET is a new clinical milestone for NETRIS Pharma. Immune-checkpoint inhibitors have revolutionized the treatment of cancer, yet the vast majority of patients do not respond or transiently respond to these immunotherapies. Based on a unique mode of action of NP137 and biomarker studies conducted in Phase 1, we believe we can enlarge the fraction of responding patients and potentially prevent resistance,” said Patrick Mehlen, CEO of NETRIS Pharma. “ImmunoNET has been specifically designed by clinicians to provide new solutions for patients suffering from resistance to immune-checkpoint inhibitors.” The study will enroll up to 90 patients suffering from solid-tumor cancers, including Head and Neck, Melanoma, Non-Small Cell Lung Cancer, Urothelial and other tumor types. These patients will be classified according to their responses to immunotherapy, in 3 arms: (1) patients under stable disease after 12 weeks under standard PD-1/PD-L1 therapy; (2) patients with radiological progression; and (3) patients with radiological progression following an initial objective response according to RECIST V1.1, with clinical benefit according to RECIST. “Despite some remarkable results with the use of immunotherapy, which have become the new standard of care in various oncology indications, many patients are experiencing an absence of response or immune resistance,” said Jérome Fayette, clinical oncologist at Centre Léon Bérard and Principal Investigator of this Investigator Initiated Trial conducted in collaboration with several key clinical centers in France. “We look forward to measure the potential benefit of NP137 on patients partially or not responding from immunotherapy.” “NETRIS Pharma is thankful to the EU Innovation Council and SME’s Executive Agency (EISMEA) to participate to the funding of this trial after having been selected as one of the most innovative project in Europe in December 2021 under the EIC accelerator Instrument program,” added Christophe Guichard, CFO of NETRIS Pharma. About NETRIS Pharma NETRIS Pharma, a clinical-stage company designs and develops anti-cancer therapeutic molecules, particularly monoclonal antibodies, to block the interaction between dependence receptors and their ligands. NETRIS Pharma, based in Lyon, is the world most advanced biopharmaceutical company targeting netrin-1. Further information can be found at: . About NP137 NP137 is a humanized monoclonal antibody of isotype IgG1 directed against netrin-1. Most types of tumors produce an abnormal amount of dependence receptors’ ligands, which prevents cells from apoptosis. Netrin-1 is overexpressed in a large percentage of human cancers. Expression of netrin-1 often correlates with disease severity and no therapy has ever been tested against this new pathway. Pre-clinical studies show NP137 to have an anti-cancer effect as a monotherapy as well as synergistic effects in combination with chemotherapy or immune checkpoint inhibitors. Further to the confirmation of the excellent safety pro human, NETRIS Pharma is simultaneously actively recruiting up to 240 patients in a separate randomized Phase 2 GYNET trial, in uterine cancer indications, in combination with chemotherapy and immunotherapy. About Centre Léon Bérard Centre Leon Berard is among the top 3 Comprehensive Cancer Center in France and an integrated cancer research site (SIRIC), with a high level of excellence in basic, translational and clinical research in oncology. It is accredited by the Organization of European Cancer Institutes (OEIC) and hosts the Cancer Research Centre of Lyon (CRCL – U1052 – UMR5286), with more than 500 collaborators involved in all domains of cancer research. Further information can be found at: ; . About EIC Accelerator The EIC Accelerator supports individual Small and Medium Enterprises (SMEs), in particular Startups and spinout companies to develop and scaleup game-changing innovations. ImmunoNET is co-funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or NETRIS Pharma. Neither the European Union nor NETRIS Pharma can be held responsible for them. View source version on businesswire.com: Contacts NETRIS Pharma Patrick MEHLEN, CEO, patrickmehlen@netrispharma.com Christophe GUICHARD, CFO and IR, christopheguichard@netrispharma.com Mike Sinclair, Halsin Partners (for NETRIS Pharma) msinclair@halsin.com Centre Léon Bérard Press Office: +33 (0) 4 69 85 61 85 julie.colomb@lyon.unicancer.fr Source: NETRIS Pharma View this news release online at: