Objective: This study was performed to search for therapeutic agents for GBA1-related α-synucleinopathy.
Background: The GBA1 gene is the causative gene of Gaucher’s disease (GD). Recently, heterozygous mutations in GBA1 are known to be a strong risk factor for Parkinson’s disease (PD). In addition, non-neuronopathic GD has also been shown to develop PD at a high rate. However, there is still no disease modifying therapy for these disease. Previously, we have reported that the GBA1 knock-out (KO) medaka display abnormal swimming movement, non-selective neuronal loss, and α-synuclein accumulation in the brains. These GBA1 KO medaka are useful to investigate the research on GBA1-related disorder. In the present study.
Method: We have established a system in which candidate compounds are administered to GBA1 KO medaka before the onset of motor symptoms. Briefly, each candidates were administered to GBA1 KO medaka from the 4 weeks post-fertilization, prior to the onset of motor symptoms, and the survival rate were analyzed.
Results: To date, the drug screening has been performed on six compounds.
Of the six compounds, survival was prolonged in two of them. In the other two compounds, survival was worsened. The remaining two compounds showed no change compared to the vehicle group.
Conclusion: Our established methods using GBA1 KO medaka were useful to investigate the efficacy of compounds. These compounds which resulted in prolonged survival may be a new disease modifying treatment for GBA1-related α-synucleinopathy. In future plan, histological and biochemical analysis will be performed.
References: Uemura, N., Koike, M., Ansai, S., Kinoshita, M., Ishikawa-Fujiwara, T., Matsui, H., Naruse, K., Sakamoto, N., Uchiyama, Y., Todo, T. et al., 2015. Viable neuronopathic Gaucher disease model in Medaka (Oryzias latipes) displays axonal accumulation of alpha-synuclein. PLoS Genet., 11, e1005065.
To cite this abstract in AMA style:
E. Nakanishi, M. Sawamura, Y. Taruno, N. Uemura, H. Yamakado, R. Takahashi. The potential of GBA1 knock-out medaka as a model animal in the search for therapeutic compounds for GBA1-related α-synucleinopathy [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/the-potential-of-gba1-knock-out-medaka-as-a-model-animal-in-the-search-for-therapeutic-compounds-for-gba1-related-%ce%b1-synucleinopathy/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-potential-of-gba1-knock-out-medaka-as-a-model-animal-in-the-search-for-therapeutic-compounds-for-gba1-related-%ce%b1-synucleinopathy/