University of Iowa recently received a five-year, $18 million grant from the National Institute of Neurological Disorders and Stroke to continue an exciting, decade-long research initiative centering on unlocking a potential cure for Huntington’s disease. Led by Doctor Peg Nopoulos, the study focuses on brain development in children at risk for development of Huntington’s disease (HD).
A Gene Called HTT
Over the past decade, principal investigator Nopoulos and her lab have been on a mission to understand the gene that causes HD. The culprit: a gene called HTT that exhibits specific DNA repetitions that can ultimately determine if an individual will develop HD. For example, if these DNA repetitions are expanded beyond a certain threshold in an individual, this person will develop HD at some point in their life, reports University of Iowa Health Care, Carver College of Medicine.
The Original Study
Originally named “the Kids-HD program,” the study commenced in 2009 and brought over 300 participants from across the country to the University of Iowa Hospitals & Clinics for genetic testing and evaluations of brain structure and function. The Iowa team studied how the brain grows and develops in children who have the HTT gene expansion compared to those with a normal range of DNA repeats.
The University of Iowa investigators discovered that children between the ages of 6 and 18 that had experienced the gene expansion also had abnormalities in the striatum, an area of the brain known to deteriorate in HD. Although the striatum was structurally abnormal in participants as young as 6 years old, symptoms of HD don’t typically develop until adulthood, reported the University of Iowa on their website.
Dr. Nopoulos suggests that the cerebellum compensates for the striatum’s abnormalities during childhood to delay the onset of symptoms. Nopoulos noted, “Since this was the only study of its kind, this [grant] renewal will help us repeat the stud with a larger sample size and continue to evaluate the beginnings of the disease process.”
The Present-Day Study
The newly-funded study is titled the Children to Adult Neurodevelopment in Gene-Expanded Huntington’s Disease (ChANGE-HD). Its’s sponsor aims to expand the size and scope of the original study with four additional sites, including the University of Texas, Houston, University of California, Davis, Children’s Hospital of Philadelphia (CHOPS), and Colombia University. In the new study, the sponsor has expanded the age range to include participants up to the age of 30—the time it takes for the human brain to fully develop.
Major Implications of this Study
The study findings have major implications for an emerging gene therapy in Phase III clinical trials that essentially “knocks down the HD gene.” The expanded study will contribute to the ongoing discovery of treatment for patients in the early stages of the disease—as well as to build more knowledge on the effects HTT has on necessary brain development. Nopoulos noted that “Since the brain takes 30 years to mature, and we know that this gene affects brain development, we really need to understand the impact of ‘knocking down’ a gene that is involved in brain development.” She further offered, “If the gene therapy works, people are going to want to give it to young people to prevent disease and we have to know how brain development is being affected in order to do that.”
Peg Nopoulos, professor of psychiatry, neurology and pediatrics, University of Iowa College of Medicine, Member of the Iowa Neuroscience Institute
Other team members include:
Ellen van der Plas, PhD
Tim Koscik, PhD
Doug Langbehn, MD, PhD
Eric Epping, MD, PhD
David Moser, PhD
Amy Conrad, PhD