Developing Biosignatures of Parkinson's Disease Using Sense of Smell

Study Rationale:
Recent reports of "super-smelling powers" published in The Lancet Neurology has triggered the idea of a specific "musky" scent in the sebum, an oily skin secretion, of those with Parkinson's disease (PD), providing a novel basis for PD biomarker (tracks disease activity) research. Our customizable MouSensor technology allows creation of highly sensitive biosensors for specific odors by genetically increasing the sensor (receptor) activated by PD sebum. As such, we can generate PD "super-sniffer" pre-clinical models to advance the identification of early stage PD biomarkers in sebum.

Hypothesis:
Certain volatile metabolites, or hormones, cause a characteristic "musky'" scent in those with PD due to the activation of specific odorant receptors expressed by neurons that line the nasal cavity.

Study Design:
First, we plan to identify the candidate receptors that are activated by PD sebum.
Pre-clinical models will be exposed to sebum samples from individuals with PD and
age-matched controls. Following odor exposure, we will perform differential gene expression analysis using olfactory tissue from both groups and will define a list of candidate PD-responsive odorant receptors. The top candidate receptor will be cloned into the MouSensor platform to generate the first-ever PD "super-sniffer" pre-clinical model.

Impact on Diagnosis/Treatment of Parkinson's Disease:
PD "super-sniffer" models can be used as tools to help identify specific volatile molecule(s) within PD sebum, which could serve as biomarkers for early-stage PD diagnostics. By extracting sensors from PD MouSensors, we may eventually create a "bio-nose-on-a-chip" for automated screening of PD sebum samples in a non-invasive and measurable way to evaluate the success of therapies in clinical trials and/or as early-stage diagnostics.

Next Steps for Development:
Following molecular characterization of the first PD MouSensor, we plan to measure how well the sensors are activated by PD sebum. In addition, we will perform a behavioral assay (test) to measure changes in the PD-odor detection threshold in PD MouSensors. We will also test additional PD sensor candidates to identify and generate additional PD MouSensors. Ultimately, we will integrate our existing technology with chip technology to create a "PD-nose-on-a-chip."