Dr. Madeleine Sharp was awarded an HDSA Human Biology Project Fellowship in 2016 and presented her work at HDSA’s 2018 Convention in Los Angeles. Her research focuses on the cognitive and behavioral symptoms of Huntington’s disease. Read about Dr. Sharp’s work, what drew her to the field of HD research, and how she learns from and is motivated by HD families.
It has been essential. First, it has solidified collaborations with two very active HD researchers, thereby connecting me to a network of HD researchers and clinicians. Second, the grant support is allowing me to pursue a project and collect preliminary data that will then allow me to apply for larger governmental grants. Third, receiving grant support from the HDSA, where I know it was reviewed by researchers who think and care a lot about Huntington’s disease, provides me with added confidence that the proposed project is of real interest to the Huntington’s disease community.
I completed medical school at McGill University in Montreal, then neurology residency in Vancouver at the University of British Columbia. It was during my fellowship training in Movement Disorders at Columbia University in New York that I really developed an interest in Huntington’s disease. I had the opportunity to work in the HD clinic at Columbia, which is a truly incredible model of multidisciplinary care provision. In parallel, I was also pursuing research interests in cognition, to answer questions about how the brain supports basic functions like learning and memory. Working with HD patients, it became very clear how much remains unknown about HD and its impact on cognition. I became very excited about the possibility of applying what we know about the brain to help us understand why patients with HD suffer from cognitive symptoms, and how studying these symptoms might also provide some insight into what is happening in the brains of these patients.
Since my research has a clinical aspect to it, I love that it puts me in contact with patients and their families. These encounters are immensely helpful; they are opportunities to obtain feedback from patients about the research, and also opportunities to observe first-hand the cognitive and behavioral symptoms which are the focus of my research.
The biggest challenge in my work is ensuring that the questions we are asking are of direct relevance to patients with Huntington’s disease. The brain mechanisms we are studying must be relevant to helping us understand and treat symptoms that people are experiencing.
I have many great mentors, but Karen Marder, an HD neurologist and researcher, has most inspired me to work with HD patients and to pursue research questions in the field of HD. Her mentorship has been unique in that she has been an excellent role model both in her role as a clinician and as a researcher. Through her example I learned a compassionate approach to providing care that focuses on communicating directly and transparently with patients and families and I learned that to be meaningful, clinical research must address what matters to the patient.
Huntington’s disease affects a part of the brain called the striatum that we know is very important for controlling behavior. The striatum sends signals about the ‘rewards’ experienced in our environments to the rest of the brain. The ability to properly send signals about these rewards is critical because most of what we think, remember, learn and do is controlled or guided by reward: we remember positive experiences, we learn from good outcomes, we strive to do well and we pay attention to what matters.
In the early stages of the Huntington’s, most of the disease in the brain is in the striatum. If the striatum is so important for informing the rest of the brain about reward, could reward signaling be impaired in patients with Huntington’s? Also, we know that the majority of people with Huntington’s experience cognitive symptoms such as loss of motivation which could be related to abnormal reward signals in the striatum. The goal of this project is to determine if reward signaling is impaired in people with Huntington’s and whether it explains some of the symptoms of HD.
Identifying abnormal reward processing in Huntington’s patients could help us develop better pharmacologic and non-pharmacologic treatments for HD. For instance, using our reward processing tasks could provide a much more sensitive way of tracking someone’s response to an experimental treatment, especially in the early stages of the disease when motor symptoms are not yet apparent.
I try to spend as much of my free time outdoors as possible, cycling or hiking in the summer and cross-country skiing in the winter. I have the great luxury of living in Montréal where we have the most wonderful snowy winters and can even ski right in the center of the city. I also recently became a mother, which has been taking precedence over all other hobbies!