A New VMAT-2 Inhibitor NBI-641449 in the Treatment of Huntington Disease.

ABSTRACT:

Aims

To evaluate the effectiveness of a new VMAT-2 inhibitor NBI-641449 in controlling hyperkinetic movements of Huntington disease (HD) and to investigate its possible therapeutic effects.

Methods

We applied three different doses of NBI-641449 (1, 10, 100 mg/kg/day) for 2 weeks in 4-month-old YAC128 mice and wild-type (WT) mice. Rotarod performance and locomotive activities were tested during the administration of the drug. The concentration of dopamine (DA) and its metabolites was quantified in the striatal tissues by high-performance liquid chromatography (HPLC). Neuron survival in striatum and huntingtin protein aggregates were assessed with immunostaining. Expression levels of endoplasmic reticulum (ER) stress proteins were detected by immunoblotting.

Results

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SUBMITTER: Chen S 

PROVIDER: S-EPMC6495663 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature