Targeting the histamine H3 receptor may slow down early-stage Huntington’s disease
As published in the peer-reviewed journal eLife, a team of researchers from Spain found a potential new avenue for treating early-stage Huntington’s disease (HD).
According to the study, targeting the histamine H3 receptor may aid in inhibiting imbalances in dopamine signaling that result in symptoms associated with the genetic disorder.
“Because dopamine receptors are found in many normal cells throughout the central nervous system, we proposed that targeting dopamine signaling through the histamine receptor might be a more effective strategy to slow the progression of Huntington’s disease,” said David Moreno-Delgado, the study’s lead author.
In their examination of an HD mouse striatal cell model and organotypic brain slices, researchers determined that the dopamine D1 receptors implicated in the neuronal degeneration and brain cell death are mitigated by a histamine H3 receptor antagonist.
“We demonstrate that the D1R-H3R heteromer is expressed in HD mice at early but not late stages of HD, correlating with HD progression,” the co-authors explained in their findings. “In accordance, we found this target expressed in human control subjects and low-grade HD patients. Finally, treatment of HD mice with an H3R antagonist prevented cognitive and motor learning deficits and the loss of heteromer expression.”
As detailed in their findings, the Spanish research team concluded that the D1R – H3R heteromers are detrimental in dopamine signaling and may be a potential avenue for the development of treatment against Huntington’s disease.