Our bodies do a lot on autopilot — breathing, keeping our hearts going, sweating, digesting our food. But sometimes those automatic functions don’t work automatically.
So-called “autonomic dysfunction” is when that process, controlled by the autonomic nervous system, goes haywire.
23andMe’s new lead scientist for our Parkinson’s Research program, Lucy Norcliffe-Kaufmann, Ph.D., has been fascinated by that process since studying physiology for her doctoral degree at the University of Leeds.
In particular, Lucy was intrigued by fainting, which is a reflexive response triggered by the autonomic nervous system. In some cases, neurodegenerative conditions like Parkinson’s disease can damage or destroy a person’s autonomic nerves. So for some of those with Parkinson’s-related autonomic dysfunction, which among other things causes hypotension, characterized by a sudden drop in blood pressure upon standing.
Lucy has continued to study this process throughout her career as a clinical autonomic neuroscientist. She spent several years as the associate director of New York University’s Langone Health’s Dysautonomia Center, also serving as an associate professor of neurology, neuroscience, and physiology there. Most recently she worked in the private sector with Theravance, where she worked on potential treatments for hypotension, a common problem among those with Parkinson’s disease.
Her role at 23andMe marks a new chapter in her career but also a continuation of this focus on conditions related to Parkinson’s. Along with this continued attention on neurodegenerative conditions, Lucy has always put patients at the center of her work. It’s that and the richness of 23andMe’s data that drew her to 23andMe, and its groundbreaking Parkinson’s research program.
We recently sat down with Lucy virtually to talk to her about her work, Parkinson’s disease, and what she’ll be focused on at 23andMe. Her responses below have been edited for length.
What inspired you to become a scientist?
My father died of diabetes and renal failure very young. I wanted to understand diseases and make a difference. That set me on the path of clinical research.
Why did you focus your work on autonomic disorders and neurodegenerative diseases?
My Ph.D. focused on fainting, which is a reflex response triggered by the autonomic nervous system. Sometimes we would see patients with neurodegenerative diseases that destroy the autonomic nerves. After finishing my degree, I became more involved with patients who have neurological diseases and permanent malfunctioning of the autonomic nervous system that causes near-fainting each time they stand.
During your time at NYU, your research included a lot of work directly with patients and advocacy groups. Why is that important in disease research?
It’s important that we listen to the patient community to find out what’s most bothersome for those living with diseases so that our research is targeting something relevant. The patient community also needs to be aware of what research opportunities are out there, so they can make a choice whether they want to participate. Finally, I think it’s important to close the loop so that patients and caregivers can understand how the research developments translate back to their care. Patients and caregivers are a critical part of our research success. They need to be with us every step of the way.
Both at New York University and then I think when you were doing work at Theravance, you began doing more work related to genetics but also in the development of treatments. Can you explain a little about that?
At NYU, I was incredibly fortunate to spend 15-years working with a community of patients with familial dysautonomia, which is a rare Jewish genetic disease that affects the development and survival of the nervous system. These children are born without the ability to feel pain or temperature and regulate their blood pressure. When I joined NYU, familial dysautonomia was misunderstood from a neurological basis. Over the years, we helped understand what was the specific pattern of nerve loss that caused the symptoms, we partnered with the FDA’s Office of Orphan Product Development to find new therapies to treat the debilitating symptoms and worked on developing potential genetic therapies to help stop the ongoing neurological decline. This patient community shaped my research career, and for that, I will always be grateful.
At Theravance, I spent a year in industry working on developing a drug to treat orthostatic hypotension, which is a problem around 40 percent of patients with Parkinson’s disease develop due to their blood pressure falling to low levels when they stand.
What are the kinds of scientific questions or problems you are drawn to?
I’m drawn to the types of questions that don’t have easy answers. I love clinical research that comes from following the patients and observing trends or patterns that teach us about diseases. I find clinical data fascinating because it comes from the patients. It’s their story and it’s up to us to think about what that means and how we can apply our knowledge to understand and develop better treatments.
What prompted you to come to 23andMe, and what specifically interests you about the Parkinson’s research program?
I really like the idea that 23andMe is following research participants with Parkinson’s disease. I’ve worked all my career in doing natural history studies. A big draw for me was the idea that we will be keeping in touch with these patients so we can understand how they evolve and we can link that back to genetics. You can only do so much when you see a patient once. But when you follow them over time you can understand much more. It’s this part that intrigues me. Each patient is a story that contributes to our understanding of Parkinson’s disease over time. Patterns start to emerge and that can change our understanding of neurological disease.
Could you explain a little bit about what you’ll be doing in this new job?
I’ll be working within the Parkinson’s disease program to map the clinical features of patients and understand their trajectories. We call this phenotyping. Once we understand the phenotypes we can link this back to the genotype and understand why people with Parkinson’s disease develop some complications and others do not. We will also be following a group of patients that have increased genetic susceptibility to Parkinson’s disease, which allows us a key window of opportunity to understand the prodromal/early phase of the disease. The earlier we learn to spot Parkinson’s disease, the more chance we have of intervening to stop neurons from progressively dying. That’s exciting.
What is unique about 23andMe’s data set or our research model that interests you?
What’s unique is the scale of data that we have and the ability to understand how our genotype influences the risk of developing Parkinson’s disease and how it may progress. It’s an incredible opportunity to work with a team of scientists so that we can answer important clinical questions and set ourselves up for developing and testing disease-modifying therapies.
What are your hopes for the work you are doing?
My hopes are that we can make a real contribution to understanding not only the risks for developing Parkinson’s disease by following patients in the prodromal phases but also what’s happening in the lives of patients living with the disease today. I’d hope that this goes back into developing new therapies that target the core of the disease process so that we can prevent Parkinson’s disease before it emerges or preserve function and stop neurological decline for those already diagnosed.