This month's featured topic goes by several names: image-guided drug delivery, focused ultrasound-mediated drug delivery and focal drug delivery.
Exciting, multi-faceted and filled with potential, this innovative approach has been studied by scientists worldwide for nearly a decade. Many applications are being explored, yet none seems more promising than the treatment of cancer. In fact, focal drug delivery could benefit millions of cancer patients worldwide by increasing the amount of chemotherapy that reaches and penetrates tumors and by eliminating toxic side effects associated with systemically administered treatments – treatments that can adversely affect healthy tissues and organs throughout the body.
In treating cancer, focal drug delivery involves the use of chemotherapy encapsulated in microscopic carriers – such as liposomes, microbubbles, nanoparticples – that travel intact through a patient's bloodstream until they reach a targeted tumor. At the treatment site, focused ultrasound provides the energy to activate the drug carriers and release their contents. MR-imaging visualizes the target site, measures local tissue temperature and monitors accurate delivery of focused ultrasound energy.
While most research is still in the preclinical stage, the field's frontrunner, Celsion Corporation, has requested FDA permission to launch U.S. clinical trials of its investigational liposome-encapsulated drug, ThermoDox. Conducted in partnership with Philips Healthcare, those studies will investigate the use of ThermoDox in focal drug delivery treatments for patients with metastatic bone cancer. (See story below.)
In this issue, you will also read about the pre-clinical research being performed by Holger Grüll and Nathan McDannold. Both are deeply committed to the development of focal drug delivery and have made important contributions to the field.
These stories merely hint at the work underway. As reported in the Foundation's March 25 news bulletin, researchers participating in our recent invitational Focal Drug Delivery Workshop have set the stage for fast-tracking a new generation of clinical applications for cancers of the liver, brain and pancreas. Treatments for Alzheimer's and Parkinson's diseases are expected to soon follow.
Going forward, we expect interest and participation in this field to grow steadily, pushing the process of discovery further and faster than currently imagined.
Celsion and Philips plan clinical studies of focal drug delivery treatment for metastatic bone cancer
In a major development, Celsion Corporation and Philips Healthcare have requested FDA permission to launch U.S. clinical studies of a new focal drug delivery treatment for metastatic bone cancer. The method uses Celsion's ThermoDox – a heat-sensitive liposomal encapsulation of the proven and widely used cancer drug, doxorubicin – and Philips' MR-guided focused ultrasound technology.
Celsion is developing the combination of ThermoDox and high intensity focused ultrasound (HIFU) through a joint research agreement with Philips Healthcare, a division of Royal Philips Electronics.
A recent publication by Holger Grüll, Ph.D. and his colleagues has been hailed as an important development in the SonoDrugs project. Launched in November 2008, SonoDrugs is a multinational, 15-partner consortium backed by the European Union's Seventh Framework Programme (FP7) and aimed at holding the line on healthcare expenditures while providing access to state-of-the-art medical care. The consortium is developing new therapeutic options for cancer and cardiovascular disease that offer greater efficacy, reduced side effects, fewer burdens on the patient and faster recovery times than existing treatments.
As a researcher, Nathan McDannold, Ph.D. is on a quest to improve the delivery of drugs to the brain. "Most drugs don't actually get into the brain when you inject them into the body or if a person takes a pill because of the blood-brain barrier," he explains. "It places a big limitation on what drugs you can use."
In preclinical studies a decade ago, McDannold and his colleagues made an important discovery: the blood-brain barrier (BBB) could be temporarily disrupted without causing damage. Doing so involved the use of pulsed, low power ultrasound combined with small microbubbles filled with a contrast agent for ultrasound imaging.
Since then, McDannold's goal has been to translate this discovery into safe and effective patient therapies that not only treat brain disorders but also precisely target where drugs are delivered.
The last ten years have been challenging for Billy R. Williams of Fort Valley, Virginia. The former Pentagon employee, who survived the 9/11 terrorist attack, has suffered from essential tremor, a progressive and debilitating neurological disorder.
Medications controlled his tremor for a while, but eventually the shaking became so severe that Williams found it impossible to do anything with his dominant right hand. He was unable to button his shirt, eat without spilling or fill in a crossword puzzle. An avid golfer, he even needed help teeing up his ball. Referred to the University of Virginia for evaluation, he learned about various treatment options and ultimately agreed to participate in a new clinical trial. Funded by the FUS Foundation, the study is assessing the safety and initial efficacy of noninvasive MR-guided focused ultrasound as a treatment for essential tremor.
On February 25, 2011, Williams became the first essential tremor patient in the world to receive MR-guided focused ultrasound therapy, and the results were dramatically positive.
Philips Sonalleve receives CE Mark for MR-guided focused ultrasound ablation of metastatic bone cancer
During last month's meeting of the European Congress of Radiology in Vienna, Philips Healthcareannounced that its Sonalleve MR-HIFU system has received CE Marking for palliative care of patients with bone metastases. Equivalent to FDA approval in the U.S., CE Marking is recognized by countries in the European Economic Area and signifies that a product complies with the essential requirements of relevant health, safety and environmental protection legislation.
The company acknowledged that it intends to seek similar approval in the U.S.
Philips has been marketing the Sonalleve for uterine fibroid treatment since December 2009 and has installed 22 systems worldwide. The Sonalleve system uses ultrasound energy to ablate metastatic tissue and sensitive nerves around the bone, alleviating the significant pain experienced by advanced cancer patients. The system's MR imaging provides 3D planning and temperature monitoring.
Profound Medical and Siemens to conduct clinical trials for prostate cancer
Profound Medical Inc. (PMI) and Siemens Healthcare have announced plans to conduct a global, multi-site, human safety/feasibility clinical trial initiative involving early stage prostate cancer patients in Europe, the U.S. and Canada.
In making the announcement, PMI's CEO Paul Chipperton observed, "We are developing a truly unique, minimally-invasive medical device for the treatment of prostate cancer, combining the already proven clinical efficacy of ultrasound thermal therapy with the unparalleled imaging capabilities of MRI." He had previously said that the new device has the potential to treat patients three to six times faster than existing options with greater accuracy and fewer side effects.
Chipperton noted that Siemens has a global reputation for excellence in research and development and has installed its Magnetom Tim MRI Systems in all of PMI's target markets. These factors, he said, "made it a natural fit to interface the two companies' technologies to provide improved speed, precision and accuracy in the treatment of prostate cancer." According to Chipperton, the companies will each bring complementary expertise in terms of hardware, software and technical support to accelerate PMI's clinical trials.
Previously, PMI had disclosed it would launch a pilot clinical trial at two U.S. hospitals in 2011. That study is expected to treat as many as 30 patients with early stage prostate cancer.
Dates and location set for 2012 International Symposium on MR-guided FUS
The Focused Ultrasound Surgery Foundation has set the date and location for the 3rd International Symposium on MR-guided Focused Ultrasound. The meeting will be held October 14-17, 2012 at the Bethesda North Marriott Hotel & Conference Centerin Bethesda, MD, USA.
Targeted to scientists, clinicians and others interested in current and future applications of MR-guided focused ultrasound, the 2012 symposium will spotlight research and clinical developments. The program will include plenary sessions, panel and small group discussions, poster presentations and technical exhibits.
From the launching of new initiatives in reimbursement and regulatory affairs to the 2nd International Symposium on MR-guided Focused Ultrasound, 2010 was a momentous year for the FUS Foundation. Research remained our key area of investment as indicated by the invitational workshops hosted by our Brain and Drug Delivery Programs and by our funding of Research Awards and Fellowships.
Albemarle Magazine spotlights FUSF and MR-guided focused ultrasound
The February/March 2011 issue of Albemarle Magazine featured an extensive interview with FUS Foundation Founder and Chairman Neal Kassell, M.D. In addition to chronicling the Foundation's origins, the report provides an excellent overview of the potential and promise of MR-guided focused ultrasound.
The FUS Foundation's patient support organization, Fibroid Relief, has scheduled a free public education event for April 27, 2011 in Houston, Texas. The event is being organized in partnership with the focused ultrasound centers at the Methodist Hospital and at St. Luke's Episcopal Hospital.
"This is the first time that we have organized an event to support two focused ultrasound centers," said Tina Krall, Fibroid Relief executive director. "Each center uses a different device to noninvasively treat uterine fibroids. Methodist is using the FDA-approved InSightec ExAblate System, and St. Luke's is a clinical trial site for the Philips Sonalleve System."
Krall said panelists for the interactive event will include three members of the Fibroid Relief Advisory Board: Denise R. Nebgen, M.D., an OB/GYN specialist at the Methodist Hospital; Robert K. Zurawin, an associate professor in the Division of Gynecology at Baylor College of Medicine; and John H. Fischer, an interventional radiologist at St. Luke's Hospital.
Additionally, several patient advocates will participate in the panel discussion, including one woman who was treated with focused ultrasound and carried a full-term pregnancy.