Investigator Update: Nir Lipsman, MD, PhD

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Key Points

  • Dr. Lipsman is the Director of the Harquail Centre for Neuromodulation and the Focused Ultrasound Centre of Excellence at Sunnybrook Health Sciences Centre.
  • He leads the recently published clinical trial investigating focused ultrasound to deliver antibodies to patients with metastatic breast cancer.
  • This is an update of his original profile from May 2017.

Nir LipsmanDr. Nir Lipsman began his work in focused ultrasound at Sunnybrook Health Sciences Centre, where he is currently Director of Sunnybrook’s Harquail Centre for Neuromodulation and the Focused Ultrasound Centre of Excellence. An early adopter of focused ultrasound, this neurosurgeon is looking to bring noninvasive solutions to patients as quickly and safely as possible. He leads the way by collaborating with experts in a wide range of disciplines, from neurodegenerative disease to psychiatric disorders and oncology. This approach has led him and his team to several world first clinical trials using focused ultrasound, including the first experience of blood-brain barrier opening in Alzheimer’s disease, ALS, and primary and secondary brain tumors.

Read our updated Q&A with Dr. Lipsman to learn about his background, research, and clinical work.

Background

When and how did you become interested in focused ultrasound?
In 2010, I learned of exciting work that was happening at Sunnybrook, where Kullervo Hynynen, a pioneer in focused ultrasound research, was based. The prospect of an image-guided therapy that would allow us to directly interface with brain pathology piqued my interest, and we started working in earnest on a proof-of-concept trial in essential tremor. I worked closely with Michael Schwartz, a neurosurgeon at Sunnybrook, to launch the ablative program here, and we continue to work closely today.

Was your PhD thesis in focused ultrasound?
No. I finished medical school and started my neurosurgery residency in 2007. In 2010, I took a break from my training to pursue a PhD. My supervisor was Dr. Andres Lozano, a world leader in functional neurosurgery. Working with him was a major reason I decided to pursue neurosurgery and research training in Toronto. My thesis was about using deep brain stimulation (DBS) to treat refractory anorexia nervosa. There is a common link between DBS and focused ultrasound: both are approaches to accessing dysfunctional brain circuits. I ended up pursuing focused ultrasound as an important potential alternative to open approaches.

What are your areas of interest in focused ultrasound?
Because the bar to intervene in the brain needs to be appropriately high; there are risks we try to minimize and outcomes we try to optimize. I’ve always been interested in new ways to interface directly with brain pathology, especially in disorders that are not always visible on MRI or CT scans. Focused ultrasound merges the latest in diagnostic and therapeutic technologies and could offer a safer approach to conventional therapies. The prospect of directly tackling the pathology that drives brain circuit disorders, and possibly influencing their natural history, is exciting.

What mechanisms and clinical indications do you study?
We are studying both ablative and nonablative applications of focused ultrasound for a broad range of conditions. We have clinical trials at various stages for bilateral thermal ablation in essential tremor, obsessive-compulsive disorder (OCD), and depression. We also have a robust BBB opening program, where we are investigating drug delivery for a host of conditions—from Alzheimer’s disease to brain cancer. Neuromodulation is another potentially exciting field, and we are in the early stages of investigating this non-lesional approach to influencing brain circuitry.

What is the goal of your work?
We are motivated by the pursuit of safe and effective treatments for patients. There is a movement in neurosurgery now toward less invasive treatment options, and this is true for spinal, vascular, and tumor surgery, among others. The hope is that focused ultrasound will help minimize risk without sacrificing efficacy or durability. The BBB applications are entirely novel; here, focused ultrasound has the potential to specifically address some of the major obstacles to getting medications and other compounds across the BBB (size limitations). The goal is changing the natural history of these diseases, where to date we have only had largely symptomatic approaches.

What are your funding sources?
The Sunnybrook Foundation and the Harquail Centre for Neuromodulation fund much of our work through the generosity of philanthropic gifts. Our trials receive funding from the Focused Ultrasound Foundation (FUSF), which has supported our tremor and brain tumor work as well as our psychiatry trials. Together with the Weston Brain Institute, FUSF is also supporting our Alzheimer’s disease and Parkinson’s disease trials.

Research Details

Who are your team members?
I’m incredibly privileged to work with an outstanding team, without whom our work would be impossible. Dr. Kullervo Hynynen, the physicist behind our work and a pioneer of focused ultrasound, is based at Sunnybrook, and his mentorship and close partnership has been key to advancing all of these trials. A talented team of research managers, study coordinators, graduate students, post-doctoral fellows, and undergraduate students are the engine of our trials and allow us to gain momentum across multiple indications. We are fortunate to have the technical expertise a team of physicists and technicians, and we operate in a center with extensive medical expertise in the conditions that we treat. We are also grateful to the strong support we receive from our hospital and research institute and the myriad members of the technical and clinical support staff on whom we heavily rely.

What are your greatest achievements?
My children! I have a daughter who is 9 years old, a son who is 7, and an amazing, understanding wife who is a visual artist in her own right.

Professionally, so far, I would say these three: 1) launching the Harquail Centre for Neuromodulation, which brought expertise in clinical and translational neuroscience under one roof to shorten the time to therapeutic development in focused ultrasound; 2) launching the Alzheimer’s and Parkinson’s BBB opening trials; and 3) demonstrating for the first time in metastatic breast cancer that large molecule therapeutic delivery can be enhanced using focused ultrasound.

Any major disappointments?
It’s been an incredibly rewarding experience. I’m grateful that, aside from some hiccups here and there, there have not been major disappointments. Most importantly, the patients we’ve treated and enrolled so far have done well. Occasional frustrations along the way are usually related to the limitations of growth and wanting to expand our scope—like recruitment challenges for studies. As we gain momentum, the hope is to garner additional interest and support, allowing us to expand to other exciting applications in the years ahead.

What do you see as impediments to your success?
Funding. Focused ultrasound treatment for essential tremor is now publicly funded by the Ontario government, and we are in discussions to extend this coverage to other indications, such as refractory OCD, where ablative treatments are currently the standard of care. We are hopeful this will change in the next 12 months, and this will allow us to provide treatment to a larger number of patients. As with most clinical research, the regulatory, legal, and other administrative hurdles could always be made more efficient. We are incredibly fortunate, though, to have fostered excellent partnerships at our institution and with industry and others to ease this as much as possible.

What is on your research wish list?
Many things! Technical developments will help advance a major priority for us, which is investigating whether focused ultrasound can be used as a therapeutic delivery strategy in neurodegenerative diseases and cancer. We are starting to collect early data that this is indeed possible. Eliminating the need for a head shave and a stereotactic frame will also make the procedures more tolerable for patients, helping in trials where multiple treatments may be necessary. We are also interested in using focused ultrasound to modulate brain function, potentially giving us a better understanding of what ultrasound is doing at a basic neuronal level.

Did the Foundation play a role in your work?
Besides funding several of our studies, I have chaired two FUSF steering committees: one for psychiatric disorders, and one for Alzheimer’s disease. I have also attended several Foundation-organized workshops for Alzheimer’s and essential tremor and have forged rewarding collaborations with researchers in the field because of these workshops. I’ve been privileged to work with the Foundation; they are outstanding in their support of us and of Sunnybrook. A key turning point was being designated a Center of Excellence. It was a real validation of our clinical projects, and the support has been amazing.

Clinical Details

Do you have a memorable clinical story or highlight to share?
With essential tremor, the treatments never get old because the result is immediate, and patients are incredibly grateful after having suffered with the condition for so long. Seeing patients go back to their hospital beds and eat and drink without shaking is incredibly rewarding. The patients in our Alzheimer’s and Parkinson’s trials—and their caregivers—are also very inspiring. Their hope and courage in taking on a journey with many unknowns is a source of constant inspiration for us as a team.

What comes next?
We are intensely interested in using focused ultrasound to enhance therapeutic delivery in neurodegenerative diseases and cancer. We are working on trials in Alzheimer’s and Parkinson’s and looking ahead at what future work in this area would look like, including forging partnerships and collaborations with other global centers. Our work in cancer is incredibly exciting, and there is real opportunity to move the dial on some of the most common metastatic and primary brain cancers. Here too, the key will be larger trials and global partnerships; working together to enhance trial design, determining the optimal therapies to deliver, and better defining outcomes.

Past Coverage