No current treatment for disease affecting 10 million people worldwide
Parkinson’s disease (PD) is a progressive neurodegenerative disorder diagnosed in approximately 10 million people worldwide; and there is currently nothing that can be done to slow the progression of the disease. When Parkinson’s disease is initially diagnosed by neurologists based on classical movement deficits, at least 50 percent of the dopamine neurons in the brain region responsible for initiation of motion are already dead. Billions of dollars have been spent on many clinical trials that have generally failed due to the late stage of diagnosis and broad molecular heterogeneity in patient populations enrolled in clinical studies. So, what is needed is both a clearer understanding of the individual etiologies of Parkinson’s disease patients as well as biomarkers for the earlier, pre-symptomatic stages of this disease.
Enrolling patients in clinical trials earlier in the course of disease could greatly improve the chances of validating a therapy; and a reliable diagnostic tool that could distinguish between molecularly distinct subsets of parkinsonian patients could help in the design of more targeted therapeutic trials.
A new diagnostic approach to fighting Parkinson’s Disease
Mass-spectrometry based multiple reaction monitoring (MRM) assays are able to precisely quantify many proteins simultaneously. We have identifed a network of candidate biomarkers from discovery studies using unique biobank samples and bioinformatics analysis of genes and molecular pathways known to be causes of Parkinson’s disease.
These biomarkers can be used in an in vitro diagnostic (IVD) tool including stable isotope labeled standards (SIS) for peptides from dozens of proteins quantifed in a single assay. Based on these biomarker peptides, our long- term goal is to design IVD products to be prescribed by physicians both for clinical evaluation and diagnosis of patients during treatment and also during selection of patients for clinical trials in more targeted drug development programs.
The advantages of multiplexed mass spectrometry based clinical diagnostics for parkinsonian disorders include:
- Stratification of PD patients with different molecular etiologies and response to therapeutics.
- Differentiation of PD from clinically similar atypical parkinsonian disorders.
- Prediction of risk for developing PD and prediction of rate of disease progression.
- Ease of measurements at multiple time-points for determining therapeutic efficacy.
- Translation of new molecular targets into companion diagnostics for drug development.
There has been much effort towards developing biomarkers for PD, including the use of liquid assays, biopsies, or brain imaging. But imaging methods are costly and unequal with regards to availability and expertise. There are no fuid based diagnostics on the market today, although many researchers are analyzing clinical samples for levels of single proteins using antibody based assays. However, several neurodegenerative diseases exhibit similar changes in individual biomarkers, indicating that multiplexed assays
of precisely measured biomarkers will be required for robust differential diagnosis.
Our solution will allow earlier and more precise diagnosis and improve patient selection for clinical trials for disease modifying therapies, meeting critical need of patients, physicians and drug development programs.