Funded Studies
Study Rationale: Lysosomes are sub-cellular compartments responsible for clearing proteins that are prone to aggregation, a process called autophagy. Dysfunctional lysosomes with increased acidity and altered autophagy are common factors in various forms of Parkingon’s disease (PD). The major goal of this project is to develop a biomarker panel for monitoring lysosomal ionic balance, measuring autophagic processes and tracking changes in cellular RNA transcripts. This will allow us to establish a platform for our Esya PD360 as novel biomarker for PD and to develop a screen for examining the outcome of therapeutic interventions of molecules targeted at lysosomal-autophagic functions.
Hypothesis: We hypothesize that our patented breakthrough lysosome-scanning DNA nanotechnology, which detects dysfunction based on changes in ionic signatures (for pH, calcium and chloride), along with alterations in RNA transcript profiles and autophagy, could produce potential diagnostic biomarkers for PD and serve as a platform for developing and assessing pharmacological interventions.
Study Design: To understand lysosomal dysfunction in PD, we will measure the acidity and calcium concentration inside lysosomes from healthy individuals and people with PD. We will then measure changes in the RNA profile or “transcriptome” and determine the number of autophagosomes (compartments carrying cargo to lysosomes) the cells contain. These three complementary techniques will be combined into a probabilistic model to predict disease outcome. This model will be further correlated with known plasma biomarkers for PD. Further, we will test the efficacy of this platform for developing novel therapeutics by treating cells with known inhibitors of PD-related proteins and pathways.
Impact on Diagnosis/Treatment of Parkinson’s disease: Development of minimally invasive diagnostic biomarker of lysosomal dysfunction and PD transcriptomics could support diagnosis years prior to manifestation of physical symptoms. We aim to provide a first-in-class diagnostic to chemically profile PD, monitor and track disease progression and develop a lysosome-targeted pipeline for novel therapeutics.
Next Steps for Development: Should this study confirm lysosomal dysfunction and transcriptomics as a diagnostic biomarker of PD, the next step will be a preclinical feasibility study. Following that, we will undertake a large multi-center study for clinical validation and establish Esya PD360 as a screening platform for identifying novel PD therapeutics.