Huntington’s disease is a genetic progressive neurodegenerative disease with no actual cure. Medications only treat spasmodic tremors or psychiatric related symptoms. Recently scientists have described a potential new therapeutic strategy for slowing down early-stage Huntington’s disease in a new study published in eLife.

“Histamine H3R are found to be a key regulator of dopamine signaling in the brain by forming interactions with dopamine D1 receptors (D1R), thus targeting H3R activates natural regulation to correct the dopaminergic imbalance and slow down the progression of Huntington’s disease” explains lead author David Moreno-Delgado, who was a Postdoctoral Research Scientist at the University of Barcelona, Spain, at the time the research was carried out, and is now Biology Team Leader at NovAliX, Belgium.

“Histamine H3R are found to be a key regulator of dopamine signaling in the brain by forming interactions with dopamine D1 receptors (D1R), thus targeting H3R activates natural regulation to correct the dopaminergic imbalance and slow down the progression of Huntington’s disease”

David moreno-delgado, lead author

The team looked at whether these protein partners are found together in mice models of Huntington’s disease. They found that at two- and four-months-old, either healthy mice or those with asymptomatic Huntington’s disease happened to present the D1R-H3R complex. However from older mice aged six- and eight-months-old, only the mice with Huntington’s disease (now symptomatic) had fully lost D1R-H3R complexes. The individual receptors were still present, but at the most advanced stage of the disease, these proteins were no longer acting together as partners.

The team targeted D1R-H3R complexes with H3R antagonist at four months. Mice treated with H3R antagonist did not develop movement or cognitive disorders in comparison with healthy animals of the same age and D1R-H3R complexes were again present.

These findings have great potential as actually H3R antagonists exist in the market that could represent opportunities for drug repurposing in Huntington’s disease.


David Moreno Delgado is insourcing Team Leader of biology screening at NovAliX, Belgium.

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