EndoPulse System for Endoscopic Ultrasound-Guided Therapy of Pancreatic Carcinoma

描述（由申请人提供）：BioElectroMed正在开发一种名为endpulse的新型医疗设备，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在消除所有三种类型的皮肤癌，基底细胞癌和鳞状细胞癌以及黑色素瘤方面的功效。nsPEF引起肿瘤消退的机制包括增加细胞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并不是细胞特异性的，因此能有效消除皮肤肿瘤的脉冲参数也应该能有效治疗胰腺肿瘤。与其他肿瘤治疗相比，这种nsPEF应用的主要优点是它最大限度地减少了对肿瘤周围健康组织的损害。只有位于电极阵列内的细胞才会受到nsPEF的刺激而发生凋亡。主要的挑战是电极在肿瘤周围的准确位置，这将通过内窥镜超声（EUS）来完成。endpulse电极将插入内窥镜的辅助通道，并通过超声成像引导到肿瘤。在这个项目的第一阶段，我们有三个具体的目标：1)制造一个纳秒脉冲电场（nsPEF）电极，与内窥镜超声兼容，并能够将nsPEF应用于胰腺肿瘤；2)利用小鼠皮下异种移植模型，确定与endpulse电极一起触发胰腺肿瘤细胞凋亡的最佳脉冲参数；3)验证eus引导下nsPEF消融猪正常胰腺组织的安全性和可行性。第二阶段将在陈安博士的指导下在斯坦福医学中心开展临床试验。如果endoppulse能够可靠地消除胰腺癌，它将为这种致命疾病的治疗提供一个急需的突破。

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.