Objective/Rationale:
The biotech company nLife Therapeutics has designed a molecule (NLF-PD-1233) to target specific neurons in the brain to reduce expression of the protein alpha-synuclein (which clumps in the cells of people with Parkinson’s disease). This project will characterize the dose and efficacy of this molecule in a model of Parkinson´s disease (PD) vs. healthy model.
Project Description:
We will characterize the pharmacokinetic (what the body does to the drug) and pharmacodynamic (what the drug does to the body) profiles of NLF-PD-1233. We will study the processes of absorption, distribution, elimination and efficacy of the compound. The first goal of this study is to find a suitable dose via intranasal administration. We will compare the drug concentrations achieved when given through the nose to those when given directly to the brain or intravenousously. The second goal will be to characterize the efficacy of NLF-PD-1233, analyzing the knockdown of alpha-synuclein mRNA expression and alpha-synuclein protein changes. Then, we will characterize the concentration-response relationship for NLF-PD-1233 and alpha-synuclein mRNA knockdown. Theses data will be use to model the projected dose-effect relationships for larger models and for humans.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
NLF-PD-1233 may be able to slow down the progression of PD and improve motor and non-motor symptoms.
Anticipated Outcome:
At the end of this project we will have characterized the dose-effect relationship in a model of Parkinson´s disease, which will be used to model doses for human administration.
Additional Support:
The Michael J. Fox Foundation would like to acknowledge the generous contribution of the Demoucelle Parkinson Charity as a lead supporter providing funding for this project.