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Research Awards Update: Eight Preclinical Projects Initiated in the First Quarter of 2023

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Key Points The Foundation’s Research Awards Program has initiated eight preclinical studies this year. Along with improving brain treatments, the funded projects use focused ultrasound to address Parkinson’s disease, pediatric neuroblastoma, tissue healing, cancer, and more. The Foundation’s Research Awards Program initiated eight new preclinical studies in the first quarter of 2023. Along with improving brain treatments, the funded projects use focused ultrasound to address Parkinson’s disease (with gene therapy), pediatric neuroblastoma, breast cancer, liver trauma, liver cancer, uterine diseases, and tissue healing. One of the brain projects will be led by a next-generation scholar. “With so many new projects getting underway in the first quarter, it is encouraging to see such a strong start to 2023,” said Matt Eames, PhD, the Foundation’s Director of Extramural Research. “This cohort includes one of our first active preclinical gene therapy projects, which is using sonogenetics to augment stem cell therapy for Parkinson’s disease.” Each newly initiated project is listed below. Gene Therapy Sonogenetics-Enabled Spatial and Temporal Expression of Transcription Factors for Direct Programming of Human Stem Cells led by Yun Jing, PhD, at Pennsylvania State UniversityIn this project, researchers will develop a new ultrasound-based (sonogenetic) approach for addressing the current limitations of stem cell therapy for treating Parkinson’s disease. Brain Investigation of Pulse Sequences for Nanodroplet-Enhanced Focused Ultrasound Mechanical Ablation in the Rat Brain led by Swanee Douglas at Brigham and Women’s Hospital*In this next-generation scholar project, researchers will design, prepare, and perform preclinical experiments with a clinical focused ultrasound device for specialized brain applications. They will use MRI for treatment guidance and assessing treatment response. Swanee Douglas is an undergraduate student at the University of Toronto. She received the Foundation’s 2022 Global Intern Award. Immunotherapy Ultrasound-Enhanced CAR-T Cell Immunotherapy of Pediatric Neuroblastoma led by Gail ter Haar, PhD, at the Institute of Cancer Research*This project will determine whether histotripsy exposure can improve engineered CAR-T cell uptake and immunotherapy efficacy in neuroblastoma. Engineered CAR-T cells are effective against blood cancers but lack efficacy in soft tissue tumors, in part due to their low uptake. Although concomitantly administered vascular permeabilizing drugs improve tumor uptake, they remain suboptimal. Histotripsy may enhance uptake sufficiently to provide an effective treatment for pediatric neuroblastoma. Biomechanical Modulation of Inflammation with Focused Ultrasound for Breast Cancer Therapy led by Charles Caskey, PhD, at Vanderbilt UniversityTo address a knowledge gap about how pulsed focused ultrasound modulates the immune system in cancer therapy, researchers will characterize the effects of focused ultrasound immunomodulation on healthy tissue and the spleen in a mouse model. Body Focused Ultrasound–Induced Hemostasis for the Treatment of Liver Lacerations (in Swine) led by John Eisenbrey, PhD, at Thomas Jefferson University HospitalIn this project, which began in September 2022, researchers will detect active bleeding from liver lacerations with contrast-enhanced ultrasound (CEUS) and then stop the bleeding with high-intensity focused ultrasound (HIFU). The liver is commonly injured from trauma. Focused Ultrasound Targeting for Interstitial Image-Guided Conformal Destruction of Tumor Volumes led by Apatou N’Djin, PhD, at Inserm LabTAU*For this project, researchers are developing new focused ultrasound equipment for the treatment of hepatocellular carcinoma (liver cancer). They are customizing a current focused ultrasound system with an innovative, image-guided, miniaturized energy delivery device to access hard-to-reach liver cancers. Noninvasive High-Intensity Focused Ultrasound Treatment of Functional Uterine Diseases led by David Melodelima, PhD, and Benoît de la Fourniere, MD, at Inserm LabTAU*To improve the efficiency of noninvasive focused ultrasound treatment of fibroids and adenomyosis, researchers will design and build a toroidal transducer that could reduce recovery time, scarring, and the need for anesthesia during the procedure. Low Intensity Focused Ultrasound (LoFU) for the Noninvasive Triggering of Silk Scaffold Degradation led by Rosalyn Abbott-Beauregard, PhD, at Carnegie Mellon UniversityTo determine whether LoFU can assist with wound healing and tissue growth, researchers will closely monitor the healing stages of individual patients and then apply LoFU on-demand to trigger certain healing processes. *Focused Ultrasound Center of Excellence Apply for a Research Award
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Focused Ultrasound for Epilepsy: Early Pilot Results Published

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Key Points One-year follow-up results from the first two participants treated in an epilepsy clinical trial have now been published. Unilateral anterior nucleus thalamus ablation was feasible and significantly reduced or stopped focal seizures. No serious adverse events were reported, but side effects included memory loss. A Phase 1 Open-Label Trial Evaluating Focused Ultrasound Unilateral Anterior Thalamotomy for Focal Onset Epilepsy One-year follow-up results from the first two participants enrolled in a clinical trial (NCT03417297) to assess the safety, feasibility, and preliminary efficacy of unilateral focused ultrasound ablation of the anterior nucleus thalamus (ANT) in adults with treatment-refractory, focal onset epilepsy have now been published. Insightec’s Exablate Neuro focused ultrasound system was used in this open-label, single-center study designed to test safety and efficacy in patients with treatment-refractory focal or partial onset epilepsy with secondary generalization. “The goal of this clinical trial is to test whether anterior nucleus ablation is safe and determine the initial efficacy,” said the principal investigator, Vibhor Krishna, MD, Associate Professor of Neurosurgery at the University of North Carolina (UNC) Chapel Hill. “We hope to offer a treatment option for patients who refuse epilepsy surgery or implanted hardware. Certainly, this is early, and we cannot make any conclusions about the efficacy without a control group, and seizure freedom or near seizure freedom is not expected in this patient population.” Two neurologists, Nathan Fountain, MD, professor of neurology and director of the Comprehensive Epilepsy Program at the University of Virginia School of Medicine, and Robert Fisher, MD, PhD, Maslah Saul MD Professor and Director of the Stanford Epilepsy Center at Stanford University School of Medicine, are also leading this study. “This novel study demonstrates that subcortical regions of the brain that are involved in seizures can be ablated by minimally invasive focused ultrasound,” said Dr. Fountain. “If this technique is ultimately shown to be safe and effective, then it would add an important tool to the armamentarium of treatments for medication-resistant focal epilepsy.” Dr. Fisher commented that the procedure is being tested as a unilateral procedure because it poses some risk to memory. He added that the safety and efficacy of anterior thalamic ablation by focused ultrasound will only be proven by larger controlled clinical trials. Assessing early safety, feasibility, and initial efficacy produced the following outcomes: This is primarily a safety study. Participants tolerated the procedure with no new neurological deficits or serious adverse events. One participant had a decline in fluency and memory but was able to fully return to work. Feasibility was defined as the ability to create a lesion in the ANT, and the procedure successfully created ANT lesions. Efficacy over time was defined as reduction in monthly seizure frequency from baseline to 12 months. One participant rapidly became seizure free, which lasted for the 12 month follow up period. The second participant’s seizures were reduced from 90 to 100 per month to 3 to 6 per month. The study, which is funded by the Focused Ultrasound Foundation, will resume in May 2023. According to the Epilepsy Foundation, focal onset seizures (“focal seizures”) are the most common type of seizure in people living with epilepsy. They begin in one region or on one side of the brain. The cause is often unknown, but focal seizures may be caused by a head injury, brain infection, stroke, or brain tumor. Medications do not control focal seizures in about 30% of people with epilepsy. See Epilepsia
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Focused Ultrasound Versus Microwave Ablation for Liver Metastases

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Key Points Researchers conducted a study to compare high-intensity focused ultrasound (HIFU) with microwave ablation (MWA) for the treatment of small metastatic liver tumors. When compared with MWA, HIFU was safe and feasible and associated with lower hospitalization costs. Comparison of High-Intensity Focused Ultrasound and Microwave Ablation for the Treatment of Small Liver Metastatic Tumors Researchers from the Department of Hepatobiliary Surgery at Suining Central Hospital in Suining, China, conducted a retrospective study to compare high-intensity focused ultrasound (HIFU) with microwave ablation (MWA) for the treatment of small metastatic liver tumors in 58 patients hospitalized from 2016–2021. This comparative study evaluated the feasibility, safety, efficacy, and costs of each treatment. The group found HIFU to be a safe and feasible treatment for small liver metastatic tumors. When compared with MWA, HIFU was associated with lower hospitalization costs. A total of 30 patients who underwent MWA were matched and compared with 28 patients who received HIFU. The matching process employed both demographic and clinical characteristics. Treating physicians used Chongqing Haifu’s Model JC Focused Ultrasound Tumor Treatment System to provide the HIFU treatments. The MWA equipment, ECO-100A1 microwave therapeutic instrument and microwave ablation needle, was manufactured by Nanjing Yigao Microwave System Engineering Co., LTD. Although the tumor ablation rate, clinical response and control rate, time of postoperative hospitalization, rate of postoperative complications, and the 1- and 3-year survival rates were not significantly different between the two groups of patients, those in the HIFU group had the lower costs for hospitalization despite longer operation times. Because of size and location of metastatic liver lesions, surgical resection is an option for only about 15% of patients with the disease; therefore, local ablation methods, including MWA and HIFU are needed. See the Journal of International Medical Research (Open Access)
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First Patient Treated in HistoSonics’ Kidney Tumor Trial

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Key Points A new clinical trial has begun in the UK investigating histotripsy for the treatment of primary kidney tumors. HistoSonics’ Edison platform uses histotripsy to noninvasively and mechanically destroy tissue. The trial is named after the late Charles Cain, PhD, co-inventor of histotripsy and co-founder of HistoSonics. The first patient has been treated in a new clinical trial investigating the HistoSonics’ Edison platform for the treatment of kidney tumors. Edison is a sonic beam therapy system that uses histotripsy to noninvasively and mechanically destroy tissue. The new Phase I trial will assess the safety and feasibility of using histotripsy to target primary solid renal tumors in 20 participants at multiple sites throughout the UK. It is named the CAIN trial after the late Charles Cain, PhD, former Chair of Biomedical Engineering at the University of Michigan, co-inventor of histotripsy, and co-founder of HistoSonics, who passed away in March 2020. The first procedure was performed in Leeds, UK, by Professor Tze Min Wah, Senior Consultant Radiologist and Clinical Lead for Interventional Oncology Program at Leeds Teaching Hospitals NHS Trust, UK. Professor Tze Min Wah commented in the release, “I was delighted to lead the clinical team in carrying out this world’s first kidney tumor treatment using histotripsy, and [it was] a real privilege to have the trust of the patient and their family in translating this innovative technology into our clinic. The CAIN Trial represents a significant milestone for treatment of solid renal tumors with histotripsy as a needle-less technology and is a paradigm shift from this point onward.” The company also has an FDA-approved Investigational Device Exemption (IDE) trial in the US to evaluate the safety and efficacy of histotripsy in destroying targeted kidney tissue, called the #HOPE4KIDNEY trial, which is expected to begin enrollment later this year. “This first treatment is a significant milestone for the company as it represents expansion into our second active clinical application (after liver) and supports our mission to deliver histotripsy to patients who may potentially benefit from its unique capabilities,” said Mike Blue, President, and CEO of HistoSonics. Learn More About the Trial Read HistoSonics’ Press Release This trial has garnered media coverage from Aunt Minnie and Mass Device.
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