By Jessica L. Foley

Innovation is the driving force for biomedical research as we strive for health care that is safer, more effective and of greater value. Continued innovation requires collaboration, particularly in this time of limited resources, global competition and long timelines from bench to bedside. The biomedical community is recognizing the need to break down the silos that impede progress, and foundations — including the Focused Ultrasound Foundation — are realizing a need for quick and widespread dissemination of research results that will forge new partnerships among multiple stakeholders including researchers, clinicians, industry, government and patients.

Promising areas of focused ultrasound, including brain applications and cancer immunotherapy, are benefiting from this culture of collaboration. Recently, there have been many exciting developments in the field of focused ultrasound that are demonstrating the potential of this early-stage, noninvasive therapeutic technology to treat a wide range of serious medical disorders.



Due to focused ultrasound’s ability to elicit more than 18 distinct bio-effects in the body — including destroying tissue, delivering drugs in high concentrations, enhancing radiation therapy and stimulating an immune response — it is now approved or under investigation to treat more than 70 conditions ranging from neurological disorders to cancers, and beyond. Recent Food and Drug Administration approvals for the treatment of essential tremor and prostate diseases have propelled the technology into many clinics and academic medical centers around the world, expanding patient access to this exciting new therapy. As these and emerging clinical applications of focused ultrasound advance through clinical trials and gain critical regulatory approvals, and new fields of research take off, it is clear that collaboration has helped to fuel progress and bring successes at a faster pace.

The tools of a new research Paradigm
Over the last several years, foundations are playing an increasingly critical role in moving research discoveries to the clinic and to commercialization. As many companies have become more risk averse, foundations can help to de-risk innovations. The flat or declining availability of research funding from government and industry players has left a critical need. Organizations like the Focused Ultrasound Foundation have become models for how donor funding can be used to bridge the gap between laboratory research and widespread patient treatment. Foundations are driven by the needs of patients and tasked with being good stewards of their donors’ generous contributions.

To meet their mission, foundations must ensure that their financial support leads to new patient treatments as quickly as possible. This sense of urgency is where collaboration becomes essential. If stakeholders are open to sharing their experiences, ideas and important data, the field can streamline research pathways, avoid duplication and enhance the impact of individual contributions to the field.

Open science is emerging as a methodology that facilitates collaboration by making important research products —experimental design, research data, preprints of publications — freely available as soon as possible. It has become too common in medical research to guard individual work closely, for a host of reasons, but that mentality can complicate and delay progress. A more open and collaborative culture is necessary to get to the finish line as quickly as possible. Government “big science” initiatives such as the Precision Medicine Initiative and the Cancer Moonshot have put a spotlight on promoting open science, particularly data sharing. Widespread accessibility of important data is necessary to meet their big goals — like achieving a decade’s worth of cancer progress in five years.

In addition to government, many private organizations that are passionate about driving progress — including the Focused Ultrasound Foundation — see open science as central to this mission and are employing open science practices and policies to govern the research projects they fund. Encouraging the use of open-access data repositories, establishing multi-site consortia to answer critical questions and making preprints of important publications widely available, among other practices and policies, will drive progress.

Making the case for collaboration: the essential tremor story
This past year brought a key turning point for the field of focused ultrasound when the FDA approved the treatment of essential tremor, marking the first use of the technology for treating the brain to be approved in the U.S. With this procedure, magnetic resonance imaging is used to guide multiple beams of ultrasound energy with extreme precision to a point in the central part of the brain.

At the point where the beams converge, the tissue is heated and destroyed in order to alleviate the tremor. The painless procedure can be performed without anesthesia, and it avoids incisions, burr holes in the skull or placement of electrodes in the brain, thus decreasing the risk of complications like infection or blood clots. The essential tremor approval opens the door in the U.S. to the treatment of other movement disorders, as well as psychiatric disorders, using precise ablation of known targets in the brain.

After FDA approval in July 2016, the Centers for Medicare & Medicaid Services established a payment for the facility component of the procedure that went into effect this year. The next step is to approach both regional Medicare intermediaries and private insurance companies to cover and reimburse the treatment, which will ultimately allow a great number of patients access to this innovative treatment.

The timeline printed on the next page shows the eight-year pathway of focused ultrasound for the treatment of tremor and the Focused Ultrasound Foundation’s role in its progress. Collaboration has been key to accelerating the timeline to bring this new treatment to patients as quickly as possible. From the early days of this effort, the collective discussion of multiple stakeholders in workshops and meetings convened by the Foundation helped to develop the road map. These early discussions identified essential tremor as a good target for focused ultrasound treatment and designed the first clinical trial.

Public-private partnerships between the Foundation, industry and academic institutions enabled the funding of the pilot and pivotal clinical trials. The pivotal trial involved eight prominent academic sites and brought together neurosurgeons, neurologists and their teams from around the world to assess the safety and efficacy of this therapy. Engagement with patient advocacy organizations helped to raise awareness for the new treatment as the pivotal trial recruited patients and preliminary results were published. Early release and widespread accessibility of data from these important clinical trials has enabled additional trials for other brain indications as well as technical, projects to improve the focused ultrasound procedure.

Having learned valuable lessons from the essential tremor pathway, the field is branching out to treat other neurological conditions. Clinical trials are ongoing in the U.S. for Parkinson’s tremor and dyskinesia and epilepsy, and are on the horizon for OCD, depression and dystonia. With continued collaboration within the growing focused ultrasound community of researchers, clinicians, manufacturers, foundations and other stakeholders, rapid progress is expected.

On the horizon
Recent developments demonstrate focused ultrasound’s reach far beyond that of a simple tool for ablation. The first-in-human trial using it to noninvasively and temporarily open the blood-brain barrier (BBB) is ongoing, enabling more effective delivery of chemotherapy into patients’ malignant brain tumors. In this trial, a chemotherapy agent and gas-filled micro-bubbles are infused into the bloodstream of a patient with a brain tumor. Focused ultrasound is applied to areas in the tumor and surrounding brain, causing the micro-bubbles to vibrate, loosening the tight junctions of the cells that comprise the BBB and allowing delivery of the chemotherapy to the targeted tissues.

With promising early results from this trial suggesting the feasibility and safety of opening the BBB, and building on preclinical results, a pilot clinical trial for treatment of Alzheimer’s is being organized. The trial design was a collaborative effort led by the Foundation and included members of industry, scientists and clinicians from several academic sites, government and representatives from patient groups. This safety and feasibility trial should begin this year, and successful results could lead to follow-on trials investigating the efficacy of focused ultrasound with and without drugs to treat or slow the progression of Alzheimer’s.

Pre-clinical evidence is mounting demonstrating that focused ultrasound can enhance the immune response to cancer and/ or enhance the effects of promising cancer immunotherapies such as checkpoint inhibitors. In the near future, the first clinical trial testing focused ultrasound in combination with immunotherapy should begin. If successful, this study could open the door to a promising new combination approach in the treatment of advanced cancer.

The Foundation has helped to advance this burgeoning field, in part, through partnering with other organizations including the Cancer Research Institute. To understand the results of early clinical trials and to inform the design of future trials, the field still needs to answer key questions about the different bioeffects (parameters, mechanism of action) of focused ultrasound.

To move the field forward, the Foundation has established multi-site consortia to investigate the impact of different FUS modalities on the immune response in models of glioblastoma (aggressive and malignant brain tumor), breast cancer and melanoma. By convening world-class experts from around the globe, we are able to benefit from a streamlined, collective approach. Consortia can improve research quality while drastically reducing the project timeline, allowing the group to rapidly gain critical information needed to develop robust focused ultrasound immunologic therapies.

We are in an unprecedented position to employ collaboration to drive medical innovation beyond any foreseeable limit. Digital channels and technological advances have created a world that is constantly connected, where data from one laboratory is globally accessible in a matter of seconds. When we realize that collaboration is itself the tipping point, we can envision better care and outcomes for patients around the world.

About the author: Jessica L. Foley, Ph.D., is the chief scientific officer of the Focused Ultrasound Foundation. Dr. Foley joined the Foundation in 2012 after completing a one-year AAAS Science and Technology Policy Fellowship at the National Science Foundation. Prior to that, she was the neuro projects manager and clinical marketing manager at INSIGHTEC, one of the pioneering focused ultrasound medical device manufacturers. Her experience also includes senior scientist at Medtronic. She has numerous publications, patents and presentations at academic conferences in the field of focused ultrasound. She holds a BSE in biomedical engineering from Duke University and a Ph.D. in bioengineering from the University of Washington.