COMPETITIVE EDGE

Traditional options for treating a tumor located in or on the brain include surgery, radiation, chemotherapy and existing local tumor therapy methods. Local or intratumoral methods include chemotherapy wafers, stereotactic (precise 3D guided) injections and convection enhanced deliveries using pumping devices that feed an externalized catheter from outside the patient's body. All of these methods have demonstrated limited success but have deficiencies that limit the application and/or effectiveness of therapy and reduce the quality of life of the patient. 

The MBP will be the first implantable pump used to treat gliomas and will represent the first time that an implantable pump uses a catheter for local delivery of medication to treat brain tumors. This implantable device is expected to offer an easier, more reliable and effective method for treating malignant brain tumors. Systemically applied cytotoxic agents in brain tumor medications are currently administered after determination of the maximum tolerated dose (MTD) that can be distributed more or less globally throughout the patient's body. This global administration is inefficient and often dangerous and can lead to severe, debilitating side effects. Because the MBP will administer cytotoxic agents directly to the brain tumor site rather than systemically, the MBP will enable the physician to use the optimal biological dose, which is generally greater than the MTD, thus increasing the effectiveness of the medication on malignant cells and decreasing the exposure of cytotoxins to normal tissues. 

The MBP will also provide physicians a method of treating brain tumors that does not need to take into consideration the dilution or hindrance of medicating agents caused by the blood brain barrier. Moreover, due to the active pumping mechanism, the anticancer agents reach well beyond the border of the tumor bed, which may result in a reduction of local recurrence.

A unique and potentially powerful capability of the MBP system is its ability to adjust the delivery of anticancer agents intelligently, based on the physiologic response of the tumor to therapy. Response to therapy is assessed by analyzing collected cerebral fluid from the tumor bed as well as by direct sensing of physiologic conditions within the tumor bed. The implanted control system of the MBP is designed to monitor vascular endothelial growth factor (VEGF) concentration determined by a light spectrometry sensor. Concentration of VEGF is detected by activating micropumps which circulate tumor fluid from the tumor site to the control unit. Depending on the concentration detected, the physician selects the medications and their amounts, which are regulated by the MBP control unit to locally deliver these medications via a double-lumen catheter. 

The control unit at the chest wall consists of several sensors and signal processing units as well as micropumps, valves and drug reservoirs. In addition to the VEGF spectrometer, sensors for intratumoral pressure, temperature and pH are located at the distal end of the catheter for monitoring physiological conditions at the tumor site.  These sensors are connected to a signal conditioning circuit before conversion to digital values by an Analog-to-Digital Converter. A microcontroller processes the sensor data and manages the micropumps and valves for delivery of the medication from the reservoirs. 

Pharmaco-Kinesis is currently working to miniaturize the components of the MBP.  Following miniaturization, the Company will conduct animal studies and plans to work with drug manufacturers to conduct the animal as well as human studies of the MBP.  The biological measurement of tumor response provided by the MBP is expected to enable drug manufacturers to evaluate the effectiveness of their drugs through detailed information on local delivery, dose, cycle and circadian time effects of medication, as well as pharmacokinetic and pharmacodynamic behavior. 

The state-of-the-art micropumps and electronically-actuated valves permit delivery of an accurate amount of medication as calculated by the microcontroller based on a predetermined table for pump control model parameters and delivery schedule. For resected tumors, an intracranial pouch helps penetrate the medication into the tumor tissue. The sensor data are stored locally on a flash memory chip and transmitted over a wireless radio link to the physician monitoring and control station, where the data can be logged and monitored in real time. The bi-directional radio link permits the physician to immediately gain control of the implanted system, if so desired, by sending the pump control model parameters via the user interface on the control station.