Objective/Rationale:
The development of disease-modifying therapies in Parkinson’s disease requires the availability of quantitative biomarkers for use in primary diagnosis, monitoring disease progression, patient stratification and evaluating efficacy of therapeutics in the clinic. In PD, a large body of evidence supports the development of alpha-synuclein-directed therapies and alpha-synuclein-related biomarkers.
Project Description:
IRBM Promidis applies its competencies and technology platforms to the development of highly sensitive protein quantification, enabling the assessment of specific, disease associated proteins as surrogate markers of disease progression/modification. The proposed project focuses on developing novel, ultra-sensitive assays to quantify levels of alpha-synuclein protein (and S129 phosphorylated alpha-synuclein) in samples of clinical origin, allowing a careful characterization of these proteins as biomarkers in PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Convenient and accurate translational markers of disease progression, such as those which might be based on alpha-synuclein, would significantly support and improve clinical trial design and timelines in PD. This would potentially enable improved clinical trial design through stratification of the patient population, evaluation of treatment efficacy through the monitoring of surrogate markers of disease progression and potentially lead to the identification of a novel treatment target (phosphorylated S129 alpha-synuclein).
Anticipated Outcome:
The proposed work would allow an initial evaluation of phosphorylated S129 alpha-synuclein as a surrogate marker for disease progression, through the development of ultra-sensitive assays of translational value, optimized for protein quantification in biological samples of clinical origin (blood/plasma and CSF). These assays could then be routinely employed for the profiling/stratification of PD patients as well as employed in clinical trials aimed at evaluating the efficacy of disease-modifying PD therapeutics.