Breaking Barriers In Neurosurgery and Immunotherapy
The collaboration of Dr. Francesco Prada and Dr. Frederic Padilla, both Merkin Fellows working with the Focused Ultrasound (FUS) Foundation, brings advancements in neurosurgery and surgical oncology closer to reality. Together, these brilliant scientists seek ways to optimize treating some of the most difficult and progressive brain tumors and cancers known to humankind.
To comprehend how focused ultrasound can assist in transforming the lives of those affected by brain tumors and other types of cancer, we must understand the journey of these two scientists from the root of their research into the practice, implementation and execution of their unique discoveries and solutions.
Sonodynamic Therapy (SDT)
Within the last year, Francesco Prada, M.D., recently appointed as Brain Program Director at the Focused Ultrasound (FUS) Foundation, successfully completed the first part of his study on sonodynamic therapy to take on glioblastoma – a type of diffuse brain tumor with a very poor prognosis. Glioblastoma is highly aggressive and difficult to treat as these tumors are found at the base of the brain. They are glial tumors, meaning they arise from the brain’s glial tissue – tissue made up of cells that help support and protect the brain’s neurons.
Prada’s goal is to use focused ultrasound to activate substances that are known to accumulate within the tumor. Typically, this method is used for intraoperative visualization of the tumor for surgical guidance (5-ala/fluorescein) to induce cell death in small animal glioma models. With the initial studies completed, Prada plans to start testing this technique in a larger preclinical model to determine its safety.
Prada is closely following the work of his mentor Dr. Jeffrey Elias, a neurosurgeon at the University of Virginia (UVA), to learn more about his focused ultrasound treatments for various applications, and to study his methods for patient selection.
Together with UVA neurosurgeon Dr. Yashar Kalani, Prada also received approval from UVA’s Internal Review Board to study the clinical use of microbubbles in an intraoperative environment. Several preclinical projects are set in motion to use microbubbles for both brain tumor ablations and blood-brain barrier (BBB) opening. The valuable data gathered from previous studies conducted in Italy at the Fondazione IRCCA C. Besta of Milan will help to create a chart of microbubble distribution in the
brain that will ultimately optimize ultrasound treatments.
In the brain tumor project, the primary purpose is to destroy the tumor in an intracranial glioma model, while the BBB study involves using direct microbubble visualization with contrast-enhancing ultrasound to focus on different parts of the brain.
Prada’s continued efforts to pursue technical, preclinical and clinical projects include further research on focused ultrasound as an adjunct to brain tumor surgery. The second part of the sonodynamic project will include sonicating different photoactive substances in larger animals to verify its safety, and enhance the data already collected from his previous research on small animal models.
“We are installing a focused ultrasound device at my home institution in Milan,” shared Prada. “The FUS Foundation seemed the perfect place to learn more about focused ultrasound in its many aspects while also sharing my clinical expertise toward brain applications, especially brain tumors. The environment at the Foundation has been extremely stimulating, and I had the opportunity to contact and collaborate on various projects with leaders in the field while broadening my understanding of how focused ultrasound can impact brain disease.”
Fighting Tumors Using Focused Ultrasound and Immunotherapy
Meanwhile, Merkin Fellow and FUS Foundation scientist, Dr. Frederic Padilla has been studying how focused ultrasound combined with chemotherapy and immunotherapy can help to alleviate the immunosuppressive microenvironment that tumors naturally develop to protect themselves from the body’s own immune system. The objective is to stimulate an effective immune response that will enhance immunotherapy.
Padilla originally joined the Foundation based on his research experience as an expert in tissue and bone characterization in the context of focused ultrasound. During his fellowship, he plans to initiate studying skull characterization with respect to neurosurgical applications of focused ultrasound, and explore focused ultrasound-induced immunomodulation.
Dr. Padilla’s current research also includes studying how focused ultrasound can trigger an immune response in breast cancer. Further exploration is required to determine if the combination of focused ultrasound and immunotherapy will be successful for breast cancer treatment. New projects on the horizon involve investigating how focused ultrasound can make pancreatic tumors more sensitive to immunotherapy.
Padilla is optimistic that focused ultrasound will provide the opportunity to be the ideal, non-invasive treatment strategy to treat pancreatic cancer – one of the most challenging cancers to treat. He hopes that when combined with immunotherapies, focused ultrasound will trigger or promote a therapeutic response that will result in a more efficient form of treatment.
Prada and Padilla’s partnership and ability to share resources at the Foundation will expand future research into how brain tumors respond to radiosurgery. By combining radiosurgery with focused ultrasound, they aim to treat diffuse brain tumors such as glioblastoma multiforme (GBM). Padilla stated, “During my time with the Foundation, I plan to further study blood-brain barrier opening and its relation to microbubble distribution within the brain.”
The continued support received from Dr. Richard Merkin, President and CEO of Heritage Provider Network (HPN) will allow the Foundation to create unique opportunities for researchers and scientists to work collaboratively to discover solutions that will one day transform healthcare treatment and save the lives of those affected by cancer and other fatal diseases.
To read the full details of Dr. Prada and Dr. Padilla’s research using focused ultrasound, visit the Focused
Ultrasound Foundation’s website at www.fusfoundation.org.
About Francesco Prada, M.D.
Merkin Fellow, July 2017
Brain Program Director at FUS Foundation
Dr. Prada joined the FUS Foundation as a Merkin Fellow in July 2017, being the Foundation’s first clinical fellow. Dr. Prada began practicing neurosurgery in 2000 and to date, has performed more than 500 ultrasound-guided neurological procedures. He relocated from the Istituto Neurologico Carlo Besta (also known as the C. Besta Institute) in Milan, Italy, for his original 12-month appointment. He will serve another year as the Foundation’s Brain Program Director.
As a clinical practitioner and researcher, his main interest is skull base, pituitary and neuro-oncological surgery. His research is focused on the intra-operative application of advanced ultrasound techniques, particularly on the use of microbubbles for image and therapy. He is also a member of the TheraGilo consortium, which focuses on theranostics microbubbles for cerebral glioma.
Dr. Prada’s interests also include physio pathological mechanisms of cerebral edema in high altitude mountain sickness. His current research focuses on ultrasound for the treatment of movement disorders, brain neoplasms and the blood brain barrier opening.
About Frederic Padilla, Ph.D.
Merkin Fellow, July 2017
Visiting Professor at FUS Foundation
Dr. Padilla is currently a Merkin Fellow, joining the FUS Foundation from the Laboratory of Therapeutic Applications of Ultrasound (LabTAU) in Lyon, France. He is signed on for his 12-month appointment as a Visiting Professor at the University of Virginia’s Department of Radiation Oncology while working closely with the Foundation’s scientific team.
His training includes physics and electrical engineering (MSc in Physics, PhD in Physical Acoustics, University of Paris-7; Electrical Engineering degree, Supelec, France). He obtained his Ph.D. in 1998 and then joined the French National Center for Scientific Research (CNRS) where he is under a tenure position as Research Scientist (Associate Professor). He is a Fulbright Fellow, and has been a visiting faculty in Boston University (2008) and a visiting professor at the University of Michigan (2009-2011).
His research agenda currently focuses on activation of anti-cancer immune response by therapeutic ultrasound, ultrasound molecular imaging of cancer and ultrasound cell assembly for tissue engineering.
Courtesy of the FUS Foundation