Imaging May Identify Treatment Targets in Early, Pre-Symptomatic, Stage of Huntington’s Disease

Development of MRI Markers for Premanifest Huntington’s Disease
Jun Hua, Ph.D.

Kennedy Krieger Institute

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

September 2015, for 3 years

Funding Amount:


Lay Summary

Imaging may identify treatment targets in early, pre-symptomatic, stage of Huntington’s disease

MRI imaging may be able to pick up early functional, vascular and metabolic brain changes in people with the Huntington’s disease gene, potentially providing targets for treating this devastating disease in its earliest stage.

Finding the Huntington’s disease (HD) gene 22 years ago was one of the most heralded discoveries in medicine. It held the potential that through prevention or early treatment, anyone who inherited this neurodegenerative disease gene mutation at birth would no longer be destined to catastrophic mental and physical decline in mid-life. One of the major hurdles stymieing this goal is the lack of “biomarkers” that are identifiable at the earliest stages of the disease. Such biomarkers might represent therapeutic targets of the earliest stages, when treatment might be effective. For, once structural changes are evident in the brain’s cerebral cortex and striatum (involved in reward and motivation), the disease process has proven—at least so far—to be irreversible.

Based on preliminary evidence, the Kennedy Krieger investigators hypothesize that specific cellular, metabolic, and vascular changes in the pathway connecting the brain’s cerebral cortex and striatum precede anatomical and symptom onset; that these changes are early biomarkers of HD; and, that these biomarkers can be detected using MRI imaging.

To see if their hypothesis is correct, they will perform MRI imaging in 30 people with the HD gene who do not yet have symptoms, 15 patients in the early stages of symptomatic HD, and 15 healthy volunteers. The investigators first will use an imaging technique called BOLD-fMRI to see whether sub-regions of the pathways that link the brain’s cortex and striatum have altered connections; if so, these alterations might eventually lead to motor symptoms.

Second, they will see with fMRI whether blood volume, blood flow, and oxygen metabolism in the brain are altered. Third, they will determine whether there is an overload of iron in the brain; this might be associated with early changes in energy metabolism. The changes may be subtle, but even so they would pave the way for larger-scale efforts to determine if indeed they are early HD biomarkers.

Significance: Early biomarkers would provide scientists with targets that experimental new therapies might be designed to act upon to prevent HD degeneration or slow its progression.

Investigator Biographies

Jun Hua, Ph.D.

Dr. Hua is an Assistant Professor in the F.M. Kirby Research Center for Functional Brain Imaging at Kennedy Krieger Institute and Department of Radiology at Johns Hopkins University School of Medicine. He received his master’s and doctoral degrees in biomedical engineering and electrical engineering at the Johns Hopkins University. Dr. Hua’s research focuses on the development of novel MRI technologies for in vivo functional and physiological imaging in the brain. He has been primarily working on high magnetic field (7 Tesla) human MRI methods for functional MRI and cerebral perfusion and oxygen metabolism measurements. Dr. Hua is also interested in novel MRI contrasts, such as chemical exchange saturation transfer (CEST). His team has been working to apply these techniques to detect functional, vascular and metabolic abnormalities in the brain in neurodegenerative diseases such as Huntington’s disease and in mental disorders such as schizophrenia.