Peggy C. Nopoulos

How the Huntingtin Gene Affects Brain Development

Professor of Psychiatry
Department of Neurology, University of Iowa; Carver College of Medicine

Peg Nopoulos, M.D. is Professor of Psychiatry, Pediatrics and Neurology. She is the Paul W. Penningroth Chair, and DEO and Chair of the Department of Psychiatry at the University of Iowa Hospitals in Iowa City, Iowa. Dr Nopoulos is a physician-scientist. Her clinical care consists of taking care of patients with Huntington’s Disease in Iowa’s HDSA Center of Excellence where she has worked for the past 15 years. Dr. Nopoulos’ research focuses on the study of brain and behavior. This is done using state of the art neuroimaging techniques, specifically Magnetic Resonance Imaging (MRI). Dr. Nopoulos is interested in aspects of understanding normal healthy brain such as differences in brain structure and function between the sexes as well as understanding how the brain changes with development through adolescence. In regard to HD, she is interested in studying the effects of the Huntington’s gene on brain development and is director of the Kids-HD (now ChANGE-HD) and Kids-JOHD program. The ChANGE-HD study evaluates brain structure and function in children and young adults at risk for HD and the Kids-JOHD program is the first ever neuroimaging study of JOHD subjects.

Publications Peggy C. Nopoulos >

Abstract | How the Huntingtin Gene Affects Brain Development
The current dogma of HD pathoetiology posits it is a degenerative disease affecting primarily the striatum, caused by a gain of function (toxicity) of the mutant mHTT that kills neurons. However, a growing body of evidence supports an alternative theory in which the gain of function is not toxicity, but instead a modulation of the growth and development of the striatum. This theory is predicated on the notion that HTT is known to be a vital gene for brain development, and in particular drives the development of striatal-cerebellar circuitry which, early in life, is beneficial. However, this circuitry is not built to last, and later degenerates. The end event in the disease is, of course, neurodegeneration; however, the process by which that occurs may be rooted in the pathophysiology of aberrant development.

To date, there have been multiple studies evaluating molecular and cellular mechanisms of abnormal development in HD, as well as studies investigating abnormal brain development in HD animal models. However, direct study of how mHTT could affect neurodevelopment in humans has not been approached until recent years. The current review will focus on the most recent findings of a unique study of children at-risk for HD, the Kids-HD study. This study evaluates brain structure and function in children ages 6–18 years’ old who are at risk for HD (have a parent or grand-parent with HD).