Study Rationale: Genetic defects in the gene encoding alpha-synuclein cause the protein to aggregate in the brains of people with a familial form of Parkinson’s disease (PD). We have developed a novel oral treatment, called ASN51, that reduces alpha-synuclein aggregation. The molecule has already shown promise in one preclinical model of PD. In this study, we seek to confirm our prior findings using another genetic preclinical model that displays alpha-synuclein aggregation. Because ASN51 is already in clinical trials for humans, the outcome of this study would provide additional critical support to justify much larger clinical trials with ASN51 in people with PD.
Hypothesis: We anticipate that ASN51 will protect the brain and improve motor function and anxiety in the alpha-synuclein A53T mouse model of PD.
Study Design: A53T is a mouse model of PD that displays abnormal alpha-synuclein aggregation. These mice will be treated with ASN51 at different doses or with a placebo for five months. At the beginning, middle and end of the treatment period, the animals will be tested for motor function and anxiety. After the last dose is given, brain tissue will be carefully studied to determine whether treatment with ASN51 prevents alpha-synuclein aggregation and brain injury compared to placebo.
Impact on Diagnosis/Treatment of Parkinson’s disease: The project has the potential to lead to the development of a new treatment for PD capable of slowing down or halting the progression of the disease.
Next Steps for Development: If successful, the next steps after this study will be the initiation of a large clinical trial in people with PD; volunteers will be given an ASN51 pill once a day and monitored over time to see whether the drug reduces motor symptoms and anxiety.