Dopamine transporter knockout mice as a screening tool for anti-parkinsonian and anti-dyskinetic agents
Unmet Need
The dopamine precursor L-DOPA is the primary treatment for Parkinson's Disease (PD). However, in addition to alleviating motor deficits associated with PD, 50-90% of patients experience side effects such as dyskinesia after 5-10 years of treatment. Lack of treatment options for PD and to mitigate dyskinesia stem from poor screening tools and animal models with PD pathogenesis that make studying new therapeutics challenging.
Technology
Duke inventors have created a novel mouse model that can be used to assess the therapeutic efficacy of novel PD drugs and anti-dyskinetic agents through behavoral screening. Specifically, the mouse model was generated by injecting previously established dopamine transporter knockout mouse model (DAT-KO) with alpha-methyl-p-tyrosine, which prevents the conversion of tyrosine to L-DOPA. Mice were established as models of PD and displayed phenotypes such as akinesia.
Mouse Advantages
- Reproducible, non-variable, bilateral DA depletion
- Ability to manipulate cell-specific gene expression bilaterally
- Robust behavioral assays to test therapeutic efficacy