PIEZO1

A new study unlocks the secrets of how high blood pressure (hypertension) fuels the progression of arterial disease. A new study in Advanced Science unlocks the secrets of how high blood pressure (hypertension) fuels the progression of arterial disease. Led by Professor Thomas Iskratsch, Professor of Cardiovascular Mechanobiology & Bioengineering at Queen Mary University of London, the research team exposes a novel mechanism by which elevated pressure transforms muscle cells in the arterial wall into "foam cells" -- the building blocks of plaque buildup that cripples arteries. The study focuses on vascular smooth muscle cells (VSMCs), the workhorses responsible for maintaining blood vessel tone and flow. Under the chronic stress of hypertension, VSMCs undergo a dramatic makeover. The researchers discovered that pressure alone triggers these cells to fill with lipid droplets, morphing them into foam cells -- culprits in the formation of atherosclerotic lesions, the hallmark of arterial disease. "This finding is pivotal because VSMCs make up over half of the foam cells found in arterial blockages," explains Professor Iskratsch. "Understanding how pressure flips this switch from muscle to foam cell is crucial for developing new therapies to control or reverse the buildup of these dangerous lesions." The study goes deeper, identifying the molecular machinery behind pressure's impact. Using advanced imaging techniques, researchers pinpointed a "mechanosignalling" pathway involving Piezo1, a pressure-sensitive protein, as well as changes in lipid metabolism and gene activity. This paves the way for novel therapies targeting specific pressure-sensitive points in the cell. This breakthrough research offers not only a deeper understanding of arterial disease but also exciting possibilities for future treatment strategies. By targeting the mechanisms that drive VSMC transformation into foam cells, researchers might be able to develop medications that prevent or even shrink atherosclerotic lesions. "Our findings provide a vital blueprint for developing next-generation therapies that could benefit millions suffering from the life-threatening consequences of arterial disease," concludes Professor Iskratsch. "This is a significant step forward in our journey towards a future where high blood pressure doesn't have to steal away life."

Independent mouse study conducted at Case Western Reserve University School of Medicine, published in OncoImmunology, builds on body of evidence demonstrating cryoablation can activate the body's natural immune response by enhancing CD8+ T cells, which are an important arm of immune response Data support previous studies and suggest ProSense® may produce anti-cancer benefits in humans beyond tumor destruction during cryoablation procedure CAESAREA, Israel, Jan. 3, 2024 /PRNewswire/ -- IceCure Medical Ltd. (Nasdaq: ICCM), developer of the ProSense® System, a minimally-invasive cryoablation technology that destroys tumors by freezing as an alternative to surgical tumor removal, today announced the publication of a study titled "Piezo1 facilitates optimal T cell activation during tumor challenge" in the highly influential peer-reviewed journal OncoImmunology. The study, conducted at Case Western Reserve University School of Medicine in Cleveland, Ohio, by Muta Abiff et al, utilized ProSense® for cryoablation procedures in a mouse model to explore the role of the Piezo1 protein in regulating T-cell tumor immune-mediated rejection of soft tissue tumors. The Piezo1 study involved performing cryoablation with ProSense® on tumor volumes of approximately 100 mm3 (diameter ~6 mm) using a mouse model. The cryoprobe was placed percutaneously directly on the tumor mass. The data demonstrates that cryoablation induces immune rejection by enhancing CD8+ T cell activation, a process dependent on T cell expression of Piezo1. Increased activation and responsiveness, potentially leading to a more robust immune response against abnormal cells, was detected up to 2 weeks after cryoablation, displayed as an increase in CD25 and interferon gamma (IFNγ) expression on CD8+ T cells. In the field of cryoimmunology, cryoablation is known to induce potent T cell-dependent tumor rejection. Prior independent research using ProSense® to explore cryoablation's antitumor activity includes a study titled "Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation" by Alshebremi et al published in August 2023 in the Journal of ImmunoTherapy of Cancer. The study demonstrated the unequivocal role of an ongoing and functional STING pathway as a major driver of local control and the systemic abscopal effects on advanced tumors following cryoablation. "Preclinical data from both of these independent studies demonstrate the unique mechanism of action through which ProSense® induces the activation of immune cells which are critical to increasing the potential therapeutic benefits of cryoablation against solid tumors. These benefits extend beyond the destruction of the tumor through our minimally invasive procedure, by activating the immune system for weeks following the procedure," stated IceCure's Chief Executive Officer, Eyal Shamir. "These studies pave the way for analysis of immune response in the growing number of ProSense® cryoablation investigator-initiated trials in humans. As always, we are very grateful to the doctors conducting these independent studies that explore and confirm ProSense®'s mechanism of action and its benefits for patients." About ProSense® The ProSense ® Cyroablation System provides a minimally invasive treatment option to destroy tumors by freezing them. The system uniquely harnesses the power of liquid nitrogen to create large lethal zones for maximum efficacy in tumor destruction in benign and cancerous lesions, including breast, kidney, lung, and liver. ProSense ® enhances patient and provider value by accelerating recovery, reducing pain, surgical risks, and complications. With its easy, transportable design and liquid nitrogen utilization, ProSense ® opens that door to fast and convenient office-based procedure for breast tumors. About IceCure Medical IceCure Medical (Nasdaq: ICCM) develops and markets ProSense®, an advanced liquid-nitrogen-based cryoablation therapy for the treatment of tumors (benign and cancerous) by freezing, with the primary focus areas being breast, kidney, bone and lung cancer. Its minimally invasive technology is a safe and effective alternative to hospital surgical tumor removal that is easily performed in a relatively short procedure. The system is marketed and sold worldwide for the indications cleared and approved to date including in the U.S., Europe, and China. Forward Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 and other Federal and Israeli securities laws. Words such as "expects," "anticipates," "intends," "plans," "believes," "seeks," "estimates" and similar expressions or variations of such words are intended to identify forward-looking statements. For example, IceCure is using forward looking statement in this press release when it discusses: the expected plan and progress towards completion of the follow-up on the ICE3 clinical study in February 2024; evaluating all strategies to efficiently and effectively address the FDA's comments; and the expected 5-year results passed on the interim analysis of the ICE3 trial. Historic results of scientific research and clinical and preclinical trials do not guarantee that the conclusions of future research or trials will suggest identical or even similar conclusions. Because such statements deal with future events and are based on IceCure's current expectations, they are subject to various risks and uncertainties and actual results, performance, or achievements of IceCure could differ materially from those described in or implied by the statements in this press release. The forward-looking statements contained or implied in this press release are subject to other risks and uncertainties, many of which are beyond the control of the Company, including those set forth in the Risk Factors section of the Company's Annual Report on Form 20-F for the year ended December 31, 2022 filed with the SEC on March 29, 2023, and other documents filed with or furnished to the SEC which are available on the SEC's website, . The Company undertakes no obligation to update these statements for revisions or changes after the date of this release, except as required by law. IR Contact: Email: [email protected] Michael Polyviou Phone: 732-232-6914 Todd Kehrli Phone: 310-625-4462 Logo - SOURCE IceCure Medical

Thanks to laboratory produced human mini-retinas, researchers were able to observe complex changes in the retina as they occur in macular degeneration. This enabled them to discover the so-called cell extrusion as a potential mechanism for neurodegenerative diseases. Visual cells in the human retina may not simply die in some diseases, but are mechanically transported out of the retina beforehand. Scientists from the Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) and the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden have now discovered this. For their research, they used miniature human retinas produced in the laboratory, so-called organoids. In the new issue of the journal Nature Communications, they report on their discovery, which paves the way for completely new research approaches, especially in connection with age-related macular degeneration (AMD). "This principle, known as cell extrusion, has not yet been studied in neurodegenerative diseases," says Prof. Mike Karl, who heads the research group. AMD is the main cause of blindness and severe visual impairment in Germany. It is estimated that a quarter of people over the age of 60 suffer from AMD. The macula is a special region within the human retina that is needed, among other things, for high resolution color vision. In AMD, thousands of light-sensitive visual cells, the so-called photoreceptor cells, are lost in the macula. "This was the starting point for our research project: we observed that photoreceptors are lost, but we could not detect any cell death in the retina," explains Mike Karl, who conducts research at the Dresden site of the DZNE and the CRTD at TU Dresden. "Half of all photoreceptors disappeared from the retinal organoid within ten days, but obviously they did not die in the retina. That made us curious." For the researchers -- the DZNE and the CRTD were involved, as well as the Helmholtz Centre for Environmental Research (UFZ) -- an elaborate search for the causes began. This led them to a study from 2012 (doi: 10.1038/nature10999): Jody Rosenblatt from King's College in London was the first to describe the extrusion of living cells -- the mechanical ejection of cells from epithelia. The thereby extruded cells then only die in succession. She demonstrated this mechanism in simple epithelial cells of the kidney. Mike Karl and his team now showed in their pioneering work that this extrusion can also be triggered in the much more complex retina, consisting of several different cell types, and leads to neurodegeneration. Interestingly, this cell extrusion could explain the outlying cells that have been previously reported in the ageing and diseased retina of patients with AMD and other diseases, but have not been studied in detail until now. The researchers made use of a technique they had previously developed: They worked with so-called retinal organoids -- an organ-like, three-dimensional model of the human retina grown from human stem cells in the laboratory. These organoids provide some characteristics of the human macula. The team found that two substances previously described in various neurodegenerative diseases -- the proteins HBEGF and TNF -- are sufficient to trigger degeneration in the retinal organoid. During this process, the researchers filmed the organoids in real time by so-called live imaging, considered as the gold standard for cell tracking. "We were able to capture the degeneration of photoreceptors through cell extrusion in the lab," says Mike Karl. The scientists found that this extrusion is triggered by activation of the protein PIEZO1, a sensor for biomechanical forces. That biomechanics may play a larger role in retinal degeneration is a new finding. "The retina is not known to be a biomechanically active tissue such as a muscle. It was known that diseases of the nervous system are associated with changes in the shape of cells, but to which extent biomechanical regulators are involved has not yet been studied in detail," says Karl. Thanks to the organoids, he and his team were able to observe the processes in an accelerated manner, so to speak: While it takes several years or even decades for photoreceptors to disappear in patients, such a process could now be reproduced in the laboratory in just 40 days. In the next step, the researchers now want to find out whether this mechanism occurs in human patients in the same way as in organoids. Initial findings suggest that this might be the same mechanism, but proof is still lacking. In their study, the Dresden researchers also found that pharmacological agents could prevent extrusion in an experimental setting in their model. They used a special snake venom to block the mechanosensor PIEZO1 on the cells. As a result, not only were the photoreceptors not ejected, but further pathological changes in the retina were prevented. "This gives hope for the development of future preventive and therapeutic treatments for complex neurodegenerative diseases such as AMD," Mike Karl sums up.