Helping to shape the future of focused ultrasound

Focused ultrasound is a revolutionary technology that has the capacity to transform the treatment of devastating brain diseases. Recent advances were shared by some of the world’s leading experts during the scientific lectures of the 2018 Ontario/Gairdner Foundation International Symposium, co-presented by Sunnybrook Research Institute (SRI) and the Gairdner Foundation. The future these scientists are sculpting is promising, and if the poster session that unfolded during the event is any indication, the next generation is eager to join the charge and more than equipped for the challenge.

With a Best Poster prize and a People’s Choice award up for grabs, 21 trainees presented 22 posters to passersby on Nov. 21, 2018. Among those weaving their way through the crowd were judges, who determined the Best Poster winner, which came with a $2,000 reward, and symposium attendees, who voted for their favourite poster. At the conclusion of the day, Dr. Michael Julius, vice-president of research at Sunnybrook and SRI, announced the victors on-site at TELUS Centre’s Koerner Hall, located in downtown Toronto, Ont.

Kristiana Xhima was triumphant in the Best Poster category, while Kelly Coultes collected the most votes to earn the People’s Choice award. Xhima and Coultes both hail from the lab of SRI senior scientist Dr. Isabelle Aubert. In addition to Aubert, the work presented in Xhima’s poster also involved Dr. Anurag Tandon, an associate professor at the Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto.

Xhima was selected for her poster titled “Alpha-synuclein gene silencing therapy delivered by magnetic resonance-guided focused ultrasound in a mouse model of Parkinson’s disease.” Following the event, she spoke about her win. “It is an honour and privilege to receive this award, especially when judged among highly worthy peers. It was impressive to see the variety of innovations represented in the poster presentations, including the technology itself, preclinical biology and clinical findings of focused ultrasound. Of course, it is wonderful to be recognized for all the hard work and dedication that went into this project,” she said.

“My poster demonstrates that MRI-guided focused ultrasound, combined with microbubbles, can be used to transiently open the blood-brain barrier in targeted brain regions, and thereby noninvasively and efficiently deliver a viral vector targeting alpha-synuclein, a key pathogenic protein that accumulates in Parkinson’s disease,” Xhima said. “We demonstrate a long-lasting, substantial decrease in alpha-synuclein expression in focused ultrasound-targeted brain regions, which represent areas affected in early- to mid-stage Parkinson’s disease.

“This therapeutic approach has the potential to overcome a few key challenges for clinical translation of gene therapy targeting alpha-synuclein, namely the limited penetration of viral vectors across the blood-brain barrier and insufficient distribution to affected brain regions by other drug delivery methods,” she added. This work was recently published in Movement Disorders.

Coultes, who manages Aubert’s lab at SRI, was similarly moved when she was acknowledged. “I feel honoured to have won the People’s Choice poster award. It was very special to have such a dynamic group of people all come together on the topic of focused ultrasound. I enjoyed talking about the work we do among peers, collaborators, young students and the general public. It was interesting to hear their feedback and views,” she said.

Her poster, titled “Improving therapeutic efficacy on Alzheimer’s pathology using transcranial MRI-guided focused ultrasound,” shows how the technology can be applied to increase delivery of therapeutics across the blood-brain barrier in a preclinical model of Alzheimer’s disease. “It also highlights some of the beneficial effects we see, such as an increase in newborn neurons and an improvement in working memory following treatment,” Coultes said.

“This work is important because it demonstrates the capabilities of this technology to increase bioavailability of therapeutics in a noninvasive way. It highlights some of the foundational work that was accomplished to move this technology forward to clinical trials,” she added.

Both winners also touched on the meaning of the poster competition. “One of the take-home messages from this event was the importance of communication in science. The poster session was a great way to share knowledge, gain feedback and have candid conversations about the work we are all doing to understand and advance this technology,” Coultes said.

Echoing this, Xhima, who plans to use her cash prize to cover the costs of attending future conferences, said, “The poster session was very valuable as a trainee. I am grateful for the unique opportunity to discuss my research, and the work of my peers, with a variety of people that each bring their own perspective to the question at hand—the general public, peers, as well as leading scientists working with focused ultrasound. For my own project, I will definitely take some of these ideas back to the team as next steps are being planned.”

She continued, “As a graduate student focused on preclinical research, seeing the end goal—the profound impact on patient care—was truly inspiring,” referring to the talks that presented results from clinical trials.

For both Xhima and Coultes, it’s now back to work, but with rejuvenated focus and a reinvigorated sense of purpose. “The unique format of this symposium was what made it most enjoyable for me,” said Coultes. “The opportunities we had to interact with biophysicists, clinicians, preclinical researchers and the public, and [to] hear from keynote speakers, I feel gave everyone at every level an opportunity to grow and learn. I left the symposium feeling inspired and with perspective in that we are all working toward a common goal—to change the standard of care for diseases of the central nervous system,” she said.

Xhima’s work was supported by the Canadian Institutes of Health Research (CIHR), the government of Ontario and the Weston Brain Institute. Dr. Kullervo Hynynen, who was involved in the project, was funded by the Canada Research Chair Program, CIHR and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIH). Xhima received a doctoral graduate scholarship from CIHR.

Coultes’ work was supported by the Alzheimer Society of Canada, Canadian Blood Services, CIHR, the government of Ontario, NIH, the Ontario Mental Health Foundation and the Weston Brain Institute.

The Canada Foundation for Innovation provided infrastructure support via its funding of the Centre for Research in Image-Guided Therapeutics.