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Focused Ultrasound for Neuropathic Pain: US Clinical Trial Data Published

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Key Points Final results from the first clinical trial in the US using focused ultrasound ablation to treat refractory neuropathic pain have been published. The procedure was feasible and safe and could potentially be used to reduce pain in these patients. Researchers at the University of Maryland Medical Center have published the final results from the first US clinical trial treating refractory neuropathic pain with focused ultrasound–induced central lateral thalamotomy (CLT). The publication, in the journal Neurosurgery, is titled, “Focused Ultrasound Central Lateral Thalamotomy for the Treatment of Refractory Neuropathic Pain: Phase I Trial.” Led by Dheeraj Gandhi, MD, the prospective, nonrandomized, single-arm, investigator-initiated phase I trial used Insightec’s Exablate Neuro device and was funded by the Focused Ultrasound Foundation.  Neuropathic pain is a type of chronic pain caused by nerve damage or a malfunctioning nervous system. It can cause significant disability, depression, and sleep problems. Dr. Daniel Jeanmonod in Switzerland pioneered the use of focused ultrasound for treating neuropathic pain.  The study team at the University of Maryland consisted of a multidisciplinary panel of physicians, including a neurointerventionalist, a neurosurgeon, a neurologist, and pain specialists. To achieve its main goals to assess safety and potential efficacy, the US clinical trial enrolled 10 patients with various types of neuropathic pain that had lasted longer than six months and did not respond to one or more previous interventions. The participants had a mean age of 50.9 years and symptoms that had lasted an average of 12.3 years.  Nine of the participants had a successful CLT ablation, and eight of those reached the one-year follow-up assessment. The group reported 12 mild or moderate adverse events, but no serious adverse events. After one year, pain scores had decreased by 46.3% on one scale (brief pain inventory) and by 42.8% on another (numeric rating). Their pain disability index decreased an average of 39.3%.  Two of the participants in this study, Tammy and Terri (seen in the video), shared their experiences undergoing a focused ultrasound brain treatment.  “We were pleased to see that bilateral treatment of the central lateral thalamus successfully reduced pain scores by over 40% at one year, with no major adverse side effects,” said Timothy D. Meakem, MD, the Foundation’s Chief Medical Officer. “It has traditionally been challenging for the US Food and Drug Administration (FDA) to approve treatments for subjective pain, so Dr. Gandhi is in discussions with the FDA to help determine whether a larger clinical trial will be planned.”  The researchers concluded that CLT was feasible and safe for treating neuropathic pain and that it could potentially be used to reduce symptoms of pain, especially in patients with intermittent pain or pain from stimuli that do not normally cause pain (allodynia). Medication use also decreased in some of the patients.  See Neurosurgery  See the Corresponding Commentary by Stephano Chang, MD, PhD and Ausaf Bari, MD, PhD Related Stories  Focused Ultrasound Offers Sustained Relief from Chronic Neuropathic Pain March 2023 (Swiss Study)  Investigator Profile: Howard Eisenberg, MD January 2022  A Focused Ultrasound Patient Story: Terri (Neuropathic Pain) September 2021  Focused Ultrasound Clinical Trial Patients Featured in Baltimore Sun April 2019  First Patient Treated in U.S. Neuropathic Pain Clinical Trial October 2018  Patient Finds Relief for Chronic Neuropathic Pain October 2018 (And see University of Maryland’s video of Tammy dancing after the procedure.)  Investigator Profile: Dheeraj Gandhi, MD October 2018 
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Focused Ultrasound Helps Sono-Sensitized Chemotherapy Reach and Treat Deep Tumors

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Key Points Researchers in Hong Kong developed an anti-cancer platinum prodrug called cyaninplatin and then showed that focused ultrasound could activate it. The team also conducted preclinical studies to deliver sono-sensitized chemotherapy to deep tumors. An Ultrasound-Activatable Platinum Prodrug for Sono-Sensitized Chemotherapy Schematic illustration of the working mechanism of cyaninplatin. Cyaninplatin can execute cancer cell killing and multimodal imaging guided sono-sensitized chemotherapy (SSCT) upon activation by focused ultrasound (FUS). i.v., intravenous.Source: Gongyuan Liu et al., An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy.Sci. Adv.9,eadg5964(2023).DOI:10.1126/sciadv.adg5964 To improve the delivery of chemotherapy to deeper tumors, a collaborative group of researchers based at City University of Hong Kong developed an anti-cancer platinum prodrug called cyaninplatin, and then showed that focused ultrasound could activate it within target lesions. Platinum (Pt) prodrugs have recently been used for diagnosing and treating disease, but the understanding of how mechanical forces activate metal-based anticancer agents is lacking. After developing cyaninplatin, the research team used focused ultrasound to convert it to carboplatin, a common chemotherapy drug, and presented data on potential mechanisms of the required chemical reaction. This precise and spatiotemporally controlled technique activates the cyaninplatin to damage mitochondria, which depletes intracellular reductants and induces bursts of reactive oxygen species, all of which may contribute to cell damage and death. Importantly, the prodrug also acts as a multi-imaging contrast agent, allowing for real time guidance with high-resolution ultrasound, near-infrared optical imaging, and photoacoustic CT. Interestingly, the sono-activated cyaninplatin also evoked an immune response by recruiting and activating T cells. For these experiments, the researchers designed a custom, ultrasound-guided focused ultrasound system in their laboratory. The system has integrated components from Sonic Concepts and Verasonics. The authors concluded that the use of sono-sensitized chemotherapy increased their ability to visualize and treat deep tumors: In Ex vivo and in vivo tests, the technology successfully activated cyaninplatin with a centimeter range of tissue depth. These findings have great potential for clinical translation. Focused Ultrasound Turns Chemo from Shotgun Blast to Sniper Shot, an article about this research in New Atlas, said “When fighting cancer, chemotherapy is still a bit of a blunt instrument. By combining it with soundwaves, however, researchers have found a way to turn it into more of a scalpel than a club, sparing damage to nearby tissue and the body as a whole.” See Science Advances (open source) See New Atlas
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