Study suggests new treatments for Huntington's disease

Previous studies had concentrated on the toxicity that the abnormal protein produces by forming cell-clogging aggregates in the nuclei of neurons. Most studies in animals, however, had not involved introducing the gene for full-length htt; they involved only a fragment.

In their experiments, Botas and colleagues introduced the gene for full-length abnormal human htt into the fruit fly Drosophila and studied its early effects on neural function in the flies.

They found that, before the abnormal protein produced any toxic effects in the nuclei of neurons, it caused abnormally high transmission of chemical signals, called neurotransmitters, among neurons. Such neurotransmitters are launched by one neuron across connections, called synapses, to its neighbor, triggering a nerve impulse in the receiving neuron. Besides abnormal synaptic transmission, the researchers also found that mutant htt caused neurodegeneration and degeneration in the flies’ motor ability.

“The findings described in this report unveil a mechanism of pathogenesis for expanded htt that does not require its nuclear accumulation in detectable amounts,” concluded the researchers. They wrote that the increased neurotransmission they detected “likely represents a mechanism of pathogenesis taking place at early stages of disease progression.

“These findings point to increased synaptic transmission as a therapeutic target with the potential of delaying [Huntington’s disease] onset and thus likely impacting disease progression,” they wrote. They concluded that their ability to genetically suppress the abnormal neurotransmission and neurodegeneration “further define[s] specific therapeutic targets and support[s] the idea that Ca2+ channel antagonists, and perhaps other inhibitors of neurotransmission, offer an attractive therapeutic option due to their specificity and wide usage.”

Source: Cell Press