In a new study on mice, Johns Hopkins Medicine researchers report that using MRI scans to measure blood volume in the brain can serve as a noninvasive way to potentially track the progress of gene editing therapies for early-stage Huntington’s disease, a neurodegenerative disorder that attacks brain cells. The researchers say that by identifying and treating the mutation known to cause Huntington’s disease with this type of gene therapy, before a patient starts showing symptoms, it may slow progression of the disease.

The findings of the study were published May 27 in the journal Brain.

What’s exciting about this study is the opportunity to identify a reliable biomarker that can track the potential success of genetic therapies before patients start manifesting symptoms. Such a biomarker could facilitate the development of new treatments, and help us determine the best time to begin them.
Wenzhen Duan, M.D., Ph.D., director of the translational neurobiology laboratory and professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

For the study, Duan and her team collaborated with colleagues from Kennedy Krieger Institute in Baltimore, Maryland, who developed a novel method to more precisely measure the blood volume in the brain by using advanced functional MRI scans. With the scans, they can map the trajectory of blood flow in small blood vessels called arterioles in the brains of mice engineered to carry the human huntingtin gene mutation that mirror the early stages of Huntington’s disease in humans.

Duan notes that there are many known metabolic changes in the brains of people with Huntington’s disease, and those changes initiate a brain blood volume response in the disease’s early stages. Blood volume is a key marker for oxygen supply to brain cells, which in turn supplies energy for the neurons to function. But with Huntington’s disease, the brain’s arteriolar blood volume is dramatically diminished, which makes the neurons deteriorate because of lack of oxygen as the disease progresses.

Overall, our data suggest that the cerebral arteriolar blood volume measure may be a promising noninvasive biomarker for testing new therapies in patients with Huntington’s who are yet to show symptoms of the disease. Introducing treatment in this early stage may have long-lasting benefits.


Our findings demonstrate that significant changes in arteriolar cerebral blood volumes occur before neurons start to degenerate and symptoms begin, further supporting the idea that altered cerebrovascular function is an early stage symptom in Huntington’s disease.

The goal is to delay or even conceivably prevent the manifestation of Huntington’s disease altogether.
Wenzhen Duan, M.D., Ph.D.



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