SBIR-STTR Award

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.

Thesaurus Terms:
"ablation; Accounting; Adverse Effects; Amylases; Apopain; Apoptosis; Apoptosis Pathway; Area; Aspiration, Respiratory; Biochemical; Bleeding; Blood Pressure; Blood Serum; Body Tissues; Breathing; Casp-3; Casp3; Cpp-32; Cpp32; Cpp32 Protein; Cpp32b; Cpp32beta; Cancer Death Rates; Carcinoma; Carcinoma Of The Pancreas; Carcinoma, Epidermoid; Carcinoma, Planocellular; Carcinoma, Squamous; Caspase 3, Apoptosis-Related Cysteine Protease; Cell Death, Programmed; Cell Membrane Permeability; Cells; Clinical; Clinical Trials; Clinical Trials, Unspecified; Cysteine Protease Cpp32; Data; Diagnosis; Diagnosis, Ultrasound; Diastase; Disease; Disease Remission; Disorder; Ecg; Ekg; Echography; Echotomography; Electrocardiogram; Electrocardiography; Electrodes; Endoscopes; Epithelial Neoplasms, Malignant; Epithelial Tumors, Malignant; Evaluation; Exocrine Pancreas Carcinoma; Family Suidae; Fever; Frequencies (Time Pattern); Frequency; Gastrointestinal Tract, Pancreas; Gastroscopes; Goals; Hemorrhage; Histologic; Histologically; Housing; Human; Human, General; Hyperthermia; Image; In Situ Nick-End Labeling; Incidence; Induction Therapy; Induction Of Apoptosis; Infection; Inhalation; Inhaling; Inspiration, Respiratory; Intracellular Membranes; Label; Lead; Lipase; Location; Malignant Melanoma; Malignant Pancreatic Neoplasm; Malignant Skin Neoplasm; Malignant Tumor Of The Skin; Malignant Neoplasm Of Pancreas; Mammals, Mice; Man (Taxonomy); Man, Modern; Medical Device; Medical Imaging, Ultrasound; Medical Center; Melanoma And Non-Melanoma Skin Cancer; Mice; Modeling; Monitor; Morbidity; Morbidity - Disease Rate; Mortality; Mortality Vital Statistics; Murine; Mus; Neoadj; Needles; Neoadjuvant; Neoadjuvant Therapy; Neoadjuvant Treatment; Operation; Operative Procedures; Operative Surgical Procedures; Parp Cleavage Protease; Pancreas; Pancreas Cancer; Pancreas Neoplasms; Pancreatic; Pancreatic Cancer; Pancreatic Tumor; Pancreatic Carcinoma; Pancreatitis; Patients; Pb Element; Permeability; Phase; Physiologic Pulse; Pigs; Procedures; Pulse; Pyrexia; Rmsn; Remission; Sca-1; Srebp Cleavage Activity 1; Safety; Serum; Site; Skin Cancer; Skin Cancer, Including Melanoma; Skin Neoplasms; Solid Neoplasm; Solid Tumor; Squamous Cell Epithelioma; Squamous Cell Carcinoma; Staining Method; Stainings; Stains; Stomach; Suidae; Surgical; Surgical Interventions; Surgical Procedure; Swine; System; System, Loinc Axis 4; Tunel; Technology; Testing; Tissues; Treatment Side Effects; Triacylglycerol Hydrolase; Triacylglycerol Lipase; Triacylglycerol Acylhydrolase; Tributyrinase; Triglyceridase; Triglyceride Lipase; Triolean Hydrolase; Tube; Tumor Cell; Tumor Of The Pancreas; Tumor Of The Skin; Ultrasonic Imaging; Ultrasonogram; Ultrasonography; Ultrasound Test; Ultrasound, Medical; Xenograft Model; Yama; Yama Protein; Blood Loss; Caspase-3; Clinical Investigation; Cysteine Protease P32; Diagnostic Ultrasound; Disease/Disorder; Effective Therapy; Electric Field; Epithelial Carcinoma; Febrile; Febris; Flexibility; Gastric; Heavy Metal Pb; Heavy Metal Lead; Imaging; In Vivo; Inspiration; Melanoma; Membrane Permeability; Minimally Invasive; Nano Second; Nanosecond; Neoplastic Cell; Pancreas Carcinoma; Pancreatic Neoplasm; Porcine; Prototype; Public Health Relevance; Side Effect; Sonogram; Sonography; Sound Measurement; Subcutaneous; Suid; Surgery; Terminal Nick End Labeling; Therapy Adverse Effect; Treatment Adverse Effect; Tributyrase; Tumor; Tumor Eradication; Ultrasound; Ultrasound Imaging; Ultrasound Scanning"

BioElectroMed is developing a new medical device called the EndoPulse"" that works in conjunction with an echoendoscope to deliver nanosecond pulsed electric field therapy to treat pancreatic carcinoma as well as lesions in the kidney and liver. The EndoPulse"" is designed to penetrate through the stomach wall into a pancreatic carcinoma before extending an electrode array on both sides of the tumor. We are also developing a high voltage model of the PulseCure"" nanosecond pulse generator that can generate 30 kV/cm between the two electrode arrays, exposing the entire tumor to this field strength. We have determined that the application of 500 pulses 100 ns long and 30 kV/cm in amplitude triggers apoptosis in all the human tumor cells between the electrodes and causes them to self-destruct within two weeks. We propose to complete the design and testing of both the EndoPulse"" and PulseCure"" prototypes and have the final versions manufactured under GMP for use in human clinical trials. These two instruments will then be used to ablate small regions of pancreas in pigs to demonstrate safety and efficacy prior to submitting the application to the FDA for an Investigational Device Exemption (IDE) required for the clinical trial. Once the IDE is granted, we will conduct a six-patient feasibility clinical trial at Stanford University Medical Center with Drs. Ann Chen and Subhas Banerjee acting as Co-Principal Investigators of this trial. These two gastroenterologists receive 3-4 patients per month with non-resectable pancreatic carcinomas for which there is currently no effective therapy. If the PulseCure""-EndoPulse"" system can reliably ablate pancreatic carcinomas, it would offer the first effective, non-surgical therapy for pancreatic cancer that could extend the lives of tens of thousands of patients each year.

Public Health Relevance:
This research will develop a breakthrough, minimally invasive approach to the treatment of pancreatic tumors for which current treatment options are poor and costly. This new medical device called the EndoPulse is readily extendable to treat other focal internal lesions especially in the liver, kidney and lymph nodes. The EndoPulse is guided to the internal tumor by ultrasound imaging in an echoendoscope and applies ultrashort electrical pulses that cause the tumor cells to self-destruct.