Study: Signs of Huntington Disease May Emerge Earlier in Life


Study shows a novel treatment approach that could prevent gene changes associated with the disease.

New research suggests that the effects of Huntington disease (HD) can be expressed earlier in life than previously believed and pre-symptomatic intervention may be able to prevent neurodevelopmental changes associated with the disease, according to a study published in the Proceedings of the National Academy of Sciences.

The findings suggest a novel approach to treating HD through the development of therapies that can be administered before signs of the disease appear, according to the study authors.

HD causes progressive deterioration of both mental and physical abilities, resulting from a genetic mutation of the huntingtin gene. Although the clinical symptoms of HD do not emerge until an adult reaches their 30’s or 40’s, the disease-causing mutant gene is already present during early developmental stages. According to the researchers, it may be possible to identify indicators from the disease much earlier than previously believed and partially reverse pre-HD symptoms through early intervention.

In the study, the researchers treated several litters of mice carrying the human huntingtin gene to 4 different dose regimens of Panobinostat, a drug currently used for the treatment of various cancers. According to the researchers, the drug may be able to regulate gene expression, which could potentially benefit those with HD.

The researchers studied the mice’s behavior by monitoring their vocalization, startle response, and risk-taking behavior. They determined that these behavioral abnormalities showed that symptoms of the disease were present before the full mutation commonly associated with the disease, although they were much less defined.

“Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking are accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro,” the authors wrote in the study.

Importantly, the researchers found that low-dose interventional treatment with the histone deacetylase inhibitor (HDACi) LBH589 led to significant improvement in behavioral changes and marker of dopaminergic neurotranismission, fully restoring alterations in neuronal differentiations in HD mice.

Although the treatment cannot fully reverse the gene mutation, clinical trials have shown that it may prevent gene changes associated with the expression of the disease.

“Our data support the notion that neurodevelopmental changes contribute to the prodromal phase of HD and that early, presymptomatic intervention using HDACi may represent a promising novel treatment approach for HD,” the researchers concluded.


Siebzehnrübl FA, Raber KA, Urbach YK, et al. Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition. PNAS. 2018.

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