This is how Elizabeth Finger, M.D., principal investigator of FOXY: A Phase 2 Clinical Trial of Intranasal Oxytocin for Frontotemporal Dementia (FTD), handles this randomized, double-blind, placebo-controlled study. FOXY seeks to assess the safety, tolerability, and effects of oxytocin to treat behavioral symptoms in people diagnosed with FTD.
“As we started the study, we didn’t appreciate that we would not have any idea of whether the treatment looked promising until many years after we started,” said Dr. Finger, associate professor of neurology in the Department of Clinical Neurological Sciences at Western University, London, Ontario, Canada, “Now we’ve come to accept that reality of doing a double-blind study.”
The FOXY clinical trial began recruiting participants in 2017. The study’s Data and Safety Monitoring Board should have the results from stage 1 analysis this May, allowing for stage 2 enrollment to begin in June or July 2021. The estimated date for the results is in fall 2023.
During those six years, Dr. Finger’s two daughters will have grown older. A novel coronavirus pandemic will have shut down the world, and the development of vaccines may reopen it. And other FTD studies will have begun and ended.
In the meantime, the FOXY researchers continue to perform alternately important and seemingly mundane tasks each day as they seek to find treatments and a cure for this “rotten and cruel disease that affects so many parts of someone’s life and their loved ones,” she said.
Please note that this glossary is available to help you understand the scientific terms used in this article. Glossary terms are shown in bold the first time they appear.
FINDING HER FOCUS
Growing up in a Michigan suburb, Dr. Finger said she always wanted to live in a big city. This was the impetus for attending Harvard University in Cambridge (Boston), Massachusetts, where she earned her Bachelor of Science in Biochemistry, and then going to Cornell University in New York City for her M.D.
“I think I always wanted to understand our experience of life as humans,” she said. “When I first started my undergraduate studies, I thought maybe that would be philosophy. I learned quickly that for me it wasn’t philosophy; it was biochemistry.”
During medical school, she found most of the clinical rotations fascinating. However, it was a combination of the professors and patients who crossed her path during the neurology rotation that influenced her the most.
One such instance occurred when Dr. M. Marsel Mesulam, noted neurologist who now is director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern University Feinberg School of Medicine, led rounds and told a story that related to the impact of motivation and emotion on attention.
“That piqued my interest, and has been something I’ve maintained an interest in with my research activities,” Dr. Finger said.
She also saw a case where a patient did not follow the usual pattern for language loss.
“If someone speaks more than one language and they have a stroke or brain injury, usually they lose their more recently learned languages and revert more and more to their first language,” she explained. “But we saw an unusual situation where a woman had a stroke and lost most of her first language, but the second language she had learned was relatively preserved.”
Another interesting case while on her neurology rotation involved a New York City copyeditor in his 30s who was having trouble writing the letter J.
“It turned out that he had a small lesion in the posterior occipital parietal region [of the brain] that accounted for that specific apraxia,” Dr. Finger explained.
After earning her M.D., she did an internship in internal medicine, followed by a neurology residency and a year as chief resident at Massachusetts General Hospital in Boston. These experiences helped her find her niche in the field.
“I recognized that the part of neurology that fascinated me the most was around how the brain supported our behavior and our higher-level thinking,” she said. “And how specific alterations in brain structure and function could give unusual patterns of change to how people normally behave or think.”
Specifically, she became interested in behaviors and thinking that were alien to her, which included people who are extremely antisocial and who have a repeat history of doing things that are against cultural norms and laws.
“Why would their brains, from my perspective, seemingly function so differently or perhaps be wired so differently than the majority of humans?” she wondered.
Following this interest, Dr. Finger completed a three-year clinical research fellowship in the Unit on Affective and Cognitive Neuroscience at the National Institute of Mental Health (NIMH) in Bethesda, Maryland, with Dr. James Blair, whose research focused on understanding the neuroscience behind psychopaths and individuals with high psychopathic traits.
“That was fascinating work, and certainly it was a critical time to gain a lot of research skills and training,” she said. “But then as I thought about the next steps, I landed in behavioral neurology but with the interest in the neurological changes that lead to some of those symptoms — loss of empathy, impulsive decision making, etc.”
WORK SCHEDULE & RESPONSIBILITIES
Dr. Finger starts her day with a breakfast of yogurt and fruit or cereal before tackling what is on her busy schedule. On Mondays, she has a full day in the clinic seeing patients who have been referred for possible neurodegenerative dementias. While the majority are suspected to have FTD, some have Alzheimer’s Disease and Lewy body dementia.
As the director of research for the Department of Clinical Neurological Sciences, Dr. Finger spends much of her Tuesdays handling research-related administrative work and planning ways to support the department’s clinician researchers and augment research activities.
Wednesdays, Thursdays, and Fridays she sees patients who are enrolled in FOXY and other studies who come for a research visit. She also supervises graduate students and trainees on their research projects in the lab, as well as writes grants and reviews manuscripts from collaborators. She recently collaborated on a grant application seeking funding for a potential second study for another symptomatic treatment in FTD.
Western University is also a location for several other multi-center studies in which Dr. Finger participates. This includes two Canadian longitudinal dementia cohort studies: the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Consortium on Neurodegeneration in Aging (CCNA). Additionally, they see patients as part of the worldwide Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Genetic Frontotemporal Dementia Initiative (GENFI), which has sites in Europe and Canada and is coordinated by Dr. Jonathan Rohrer at University College London, England, UK.
Western University also participates as a site in multicenter clinical trials that are sponsored by pharmaceutical companies. Dr. Finger has been involved in all three phases of Alector’s INFRONT-3, which seeks to determine if the drug AL001 will delay the onset of symptoms or slow disease progression when compared to a placebo in people who have progranulin gene mutations.
“We also do a fair bit of investigator-initiated studies in our group looking at some of the neurophysiology relating to social cognition, including emotion processing, emotional experiences, and decision-making,” she noted. “Some are behavioral and cognitive paradigms, and some are imaging paradigms. We also do a bit of PET imaging research looking both at metabolism as well as neuroinflammation in patients with FTD.”
In addition to her duties at Western University, she also works as a neurologist at the Cognitive Neurology and Alzheimer Research Centre (CNARC) at Parkwood Institute, and a scientist at Lawson Health Research Institute and Robarts Research Institute.
For her work in the field, Dr. Finger is the recipient of resident teaching awards from Harvard University, Special Act Awards for Fellows at the NIH, the Early Researcher Award from the Ministry of Research and Innovation of Ontario, and the PSI-50 Mid-Career Clinical Research Award from the PSI Foundation.
The busy life of a clinician and scientist often leaves little time for life outside of work. Dr. Finger said she likes to go cross-country skiing in the winter and in the summer play tennis, jog, and go to the beach at one of the Great Lakes. Lake Huron and Lake Erie are nearby.
“In London there are lots of lovely parks,” she said. The Canadian city is only about 100 miles from where she grew up. In addition to her husband and daughters, the family includes a Bouvier des Flandres, a very large breed of dog.
“I think like most clinician researchers, it’s hard sometimes to put work away because it’s fascinating and consuming and demanding,” she admitted. “But sometimes I do. Prior to the pandemic, the family did take vacations.”
SATISFACTION AND MOTIVATION
An aspect of the neurologist’s career that she hadn’t expected is the colleagues that she has met in the field of cognitive neurology and specifically those working in FTD.
“They are such a talented, motivated, collegial, and inspiring group,” she said. “I don’t know that you see that collegiality and collaboration in all fields, so that’s something I very much appreciate.”
Even though there currently are no treatments that are satisfactory for people diagnosed with FTD, Dr. Finger noted that direct interactions with patients and their families are a rewarding aspect of her job.
“I receive a lot of satisfaction as they’re trying to navigate this terrible illness to at least supply them with as much education and information and support going forward,” she said.
She is especially thankful for the patients who participate in trials, because without them it would not be possible to advance the science and discover effective treatments for FTD.
Finally, Dr. Finger is confident that the current students -- the next generation of scientists -- will be able to tackle the questions, continue the work begun now, and figure out answers for FTD.
“I think advances in FTD have been catalyzed by the genetic discoveries and neuropathology discoveries,” she said. “My colleagues and basic scientists are developing treatments to target, especially in the near term, those genetic causes of FTD.
“I certainly have a lot of optimism that there will be some major breakthroughs in my lifetime.”