Congratulations to Drs. Blair Leavitt and Lynn Raymond on being named recipients of the Huntington Society of Canada’s 2025 Navigator Awards!

The Navigator Research Program is designed to provide funding for Canadian scientific research projects of direct and immediate relevance to Huntington disease.

Learn more about the funded projects:

Dr. Blair Leavitt

Research Project Title: Targeted DNA methylation editing to ameliorate Huntington’s
disease phenotypes in human induced pluripotent stem cells

Lay Summary: Huntington’s disease (HD) is a brain disorder caused by a single, specific
mutation in the DNA sequence of the huntingtin gene (HTT). This mutation produces an
abnormal, toxic mutant huntingtin protein (mHTT) that causes a progressive loss of cells in the
brain and leads to the development of HD symptoms. Many factors, including naturally occurring
chemical modifications of DNA, impact levels of mHTT. In turn, mHTT levels affect the onset,
progression, and severity of HD patient symptoms. One type of chemical DNA modification,
called DNA methylation (DNAm), alters the activity of HTT in brain cells and may affect the loss of
brain cells that occurs in HD. In this proposal, we will alter DNAm at HTT to selectively reduce the
quantity of toxic mHTT protein produced from HTT, and we will evaluate how lowering toxic
mHTT using this approach improves the health of cells carrying the HD mutation. These studies
will use specialized human cells highly similar to the brain cells affected in HD, enabling accurate
assessment of how altering HTT DNAm improves cellular HD symptoms. This work will increase
our understanding of the impact of DNAm levels on toxic mHTT abundance and measure how
altering DNAm levels at HTT improves cellular HD symptoms, and will evaluate the utility of
altering DNAm as a novel approach for therapeutic mHTT lowering in HD.

Dr. Lynn Raymond

Research Project Title: Neurofeedback-Driven Restoration of Cortical Connectivity in HD
(Co-investigator: Dr. Tim Murphy)

Lay Summary: Huntington disease (HD) is traditionally viewed as a disorder of the deep brain
(the striatum), but mounting evidence shows that even before clear symptoms appear, HD
alters how different parts of the brain communicate, particularly in motor regions. In HD mouse
models, neurons in cortical motor areas not only lose connection with other regions but also
activate in a disorganized manner, impairing movement control. In our study, we will first
confirm these circuit changes and investigate whether and how they correlate with
performance in a fine motor control task (pulling a lever for water reward). Then we will test
two ways to help them “rewire” the affected motor area: one teaches mice to boost the correct
brain signals by giving them water rewards whenever they succeed (neurofeedback training),
and the other uses direct stimulation to trigger those same cells on a fixed schedule
(optogenetic stimulation). By comparing these approaches, we hope to restore coordinated
activity in the affected motor region in the cortex and improve the animal’s performance on the
motor task. If successful, this could lead to simple, noninvasive brain-training programs for
people with early-stage HD.