EndoPulse System for Endoscopic Ultrasound-Guided Therapy of Pancreatic Carcinoma

描述(申请人提供)：BioElectrMed正在开发一种名为EndoPulse的新医疗设备，该设备将提供纳秒脉冲电场(NsPEF)来治疗胰腺癌。我们有广泛的证据支持nsPEF在消除所有三种皮肤癌、基底细胞癌和鳞状细胞癌以及黑色素瘤方面的有效性。NsPEF导致肿瘤消退的机制包括增加细胞内膜的通透性和触发细胞凋亡。这种电场诱导的膜通透性增加不是细胞特有的，因此同样的脉冲参数在消除皮肤肿瘤方面有效，在治疗胰腺肿瘤方面也应该有效。与其他肿瘤治疗方法相比，这种nsPEF应用的主要优势是它将对肿瘤周围健康组织的损害降至最低。只有位于电极阵列内的细胞才会受到nsPEF应用的刺激而发生凋亡。主要的挑战是在肿瘤周围准确放置电极，这将使用内窥镜超声(EUS)来完成。EndoPulse电极将被插入内窥镜的辅助通道，并使用超声成像引导至肿瘤。在该项目的第一阶段，我们有三个具体目标：1)制造与内窥镜超声兼容的纳秒脉冲电场(NsPEF)电极，并且能够将nsPEF应用于胰腺肿瘤；2)通过小鼠皮下移植瘤模型，确定EndoPulse电极触发胰腺肿瘤细胞凋亡的最佳脉冲参数；3)证明EUS引导下nsPEF消融猪正常胰腺组织的安全性和可行性。然后，第二阶段将在陈安博士的指导下，在斯坦福医学中心启动临床试验。如果EndoPulse能够可靠地消除胰腺癌，它将在这种致命疾病的治疗方面提供亟需的突破。 与公共卫生相关：我们正在开发一种新的医疗设备，EndoPulse，用于治疗胰腺癌，目前还没有有效的治疗方法。EndoPulse将肿瘤暴露在超短电脉冲下，这些超短电脉冲渗透到细胞内的细胞膜，并引发细胞凋亡或程序性细胞死亡。这会导致胰腺癌自我毁灭。EndoPulse通过超声成像内窥镜中的辅助通道被引导到肿瘤，该辅助通道也将用于成像肿瘤周围电极的放置。通过内窥镜传递电脉冲来触发肿瘤缓解，为胰腺癌的治疗提供了亟需的突破。

DESCRIPTION (provided by applicant): BioElectroMed is developing a new medical device called the EndoPulse that will deliver nanosecond pulsed electric fields (nsPEF) to treat pancreatic carcinomas. We have extensive evidence supporting the efficacy of nsPEF in eliminating all three types of skin cancer, basal and squamous cell carcinoma and melanoma. The mechanism by which nsPEF causes tumor regression involves increasing the permeability of intracellular membranes and triggering apoptosis. This electric field-induced membrane permeability increase is not cell specific so the same pulse parameters that are effective at eliminating skin tumors should also be effective at treating pancreatic tumors. The main advantage of this nsPEF application over other tumor treatments is that it minimizes damage to healthy tissue surrounding the tumor. Only cells located within the electrode array are stimulated by nsPEF application to undergo apoptosis. The main challenge is the accurate placement of the electrodes around the tumor and this will be accomplished using endoscopic ultrasound (EUS). The EndoPulse electrodes will be inserted down the accessory channel of the endoscope and guided to the tumor using ultrasound imaging. During Phase I of this project we have three specific aims: 1) Fabricate a nanosecond pulsed electric field (nsPEF) electrode compatible with endoscopic ultrasound and capable of applying nsPEF to pancreatic tumors; 2) Determine the optimal pulse parameters to use with the EndoPulse electrode to trigger apoptosis in pancreatic tumors using a murine subcutaneous xenograft model; 3) Demonstrate safety and feasibility of EUS-guided nsPEF ablation of normal pancreatic tissue in a pig. Phase II will then launch clinical trials at Stanford Medical Center under the direction of Dr. Ann Chen. If the EndoPulse can reliably eliminate pancreatic carcinomas, it would offer a much needed breakthrough in the treatment of this deadly disease. PUBLIC HEALTH RELEVANCE: We are developing a new medical device, the EndoPulse, for treating pancreatic carcinoma for which there are currently no effective therapies. The EndoPulse exposes the tumor to ultrashort electrical pulses which permeabilize intracellular membranes and trigger apoptosis or programmed cell death. This causes pancreatic carcinomas to self-destruct. The EndoPulse is guided to the carcinoma via an accessory channel in an ultrasound imaging endoscope which will also be used to image the placement of the electrodes around the tumor. Endoscopically delivered electrical pulses to trigger tumor remission offers a much needed breakthrough in the treatment of pancreatic cancer.