A Neural Implant for Cytostatic Hypothermia in Swine (P4-5.008).

in Neurology by Syed Faaiz Enam, Mahabad Barwari, Aksharkumar Dobariya, Reed Chen, Ravi Bellamkonda, Toral Patel, Ankur Patel

TLDR

  • Researchers have developed an implantable device that uses temperature control to stop brain cancer from growing, showing promise in early animal testing and potential for future human clinical trials.

Abstract

To develop an implantable device capable of delivering intracranial cytostatic hypothermia in swine. Patients with glioblastoma (GBM) require novel approaches to treatment. We have previously demonstrated that intra-tumoral, non-freezing, 'cytostatic' hypothermia, can safely stunt GBM growth and effectively prolong survival in rodents with GBM. This was demonstrated through a device consisting of a thermoelectric cooler, probe, heat sink, and fan. Unlike targeted therapeutics that are successful in preclinical models but fail in clinical trials, cytostatic hypothermia leveraged fundamental physics that influenced biology broadly. This makes biological translation more feasible but engineering challenges to larger animals and eventually patients remain unsolved. Here we used finite element modeling to simulate heat transfer in a fully implantable system that incorporates corporal fluid-based heat distribution. We then designed devices consisting of a multiprobe array and artificial internal circulation system. Devices were successfully fabricated via CAD software, a desktop CNC machine, and a 3D printer. They were tested under lab conditionsand thenin anesthetized swine. Modeling demonstrated that a multi-probe array strategy could homogenously cool a region of brain tissue to 25°C. The heat transferred out of the tissue did not raise skin temperature by >3°C from baseline (the temperature at which continuous exposure could induce thermal damage).testing validated these findings. Subsequent testing in anesthetized pigs successfully reached the target temperature that would otherwise be cytostatic: 25°C, without heating the skin by >3°C from baseline. The power source and data collection were also made fully portable, paving the way for survival surgeries. Cytostatic hypothermia is effective in prolonging the survival of rodents with GBM. Here we have demonstrated that this approach can be scaled to larger animals and made implantable. Both these characteristics bring this novel approach closer to becoming a real option for patients with GBM.Dr. Enam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Emory University. Dr. Enam has stock in Thermeutics, LLC. Dr. Enam has received intellectual property interests from a discovery or technology relating to health care. Ms. Barwari has nothing to disclose. Mr. Dobariya has nothing to disclose. Mr. Chen has received intellectual property interests from a discovery or technology relating to health care. Prof. Bellamkonda has nothing to disclose. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Elekta. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GT Medical Technologies. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Elekta. Dr. Patel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GT Medical Technologies. An immediate family member of Dr. Patel has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Mann Morrow, PLLC. The institution of Dr. Patel has received research support from NINDS. The institution of Dr. Patel has received research support from NIH/NCI. The institution of Dr. Patel has received research support from CPRIT. The institution of Dr. Patel has received research support from NIH/NCI. The institution of Dr. Patel has received research support from Ben and Catherine Ivy Foundation. Dr. Patel has received intellectual property interests from a discovery or technology relating to health care. Dr. Patel has nothing to disclose.

Overview

  • The study aims to develop an implantable device capable of delivering intracranial cytostatic hypothermia in swine, a novel approach for treating glioblastoma (GBM).
  • The device uses thermoelectric cooling, a probe, heat sink, and fan to safely stunt GBM growth and prolong survival in larger animals. Finite element modeling was used to simulate heat transfer and design the device.
  • The primary objective is to demonstrate the scalability of this approach to larger animals and make it implantable, bringing it closer to becoming a treatment option for patients with GBM.

Comparative Analysis & Findings

  • The study demonstrates that a multi-probe array strategy can homogenously cool a region of brain tissue to 25°C, making it suitable for cytostatic hypothermia.
  • The device successfully cooled the brain tissue to 25°C without raising the skin temperature by >3°C from baseline, meeting the safety criteria.
  • The study shows that the device can be powered and designed for survival surgeries, paving the way for further development and potential clinical applications.

Implications and Future Directions

  • The development of an implantable device for cytostatic hypothermia has the potential to revolutionize the treatment of GBM and other brain tumors.
  • Future studies can focus on testing the device in larger animal models and eventually in human clinical trials to further validate its safety and efficacy.
  • The device's scalability and implantability make it a promising approach for treating other types of brain tumors and diseases, warranting further research and exploration.
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