Clinical Diagnostics and Research May 28-30, 2014

Anthony Marotta, PhD

Chief Scientific Officer, Augurex Life Sciences Corp

How does the soluble mechanistic biomarker 14-3-3 eta assist in the management of Rheumatoid Arthritis?

   Dr. Anthony Marotta is a co-founder and the Chief Scientific Officer for Augurex Life Sciences, a company that is focused on the development of the 14-3-3 eta personalized medicine opportunity for the management of specific forms of arthritis including: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). In 2013 through Dr. Marotta's leadership, Augurex received Health Canada approval and CE approval for their first diagnostic assay, the 14-3-3 eta ELISA that measures the level of the 14-3-3 eta protein in serum/plasma. Prior to co-founding Augurex, Dr. Marotta served as the Director of Business Development for Stressgen Bioreagents, a company that focused on providing research tools in the area of signal transduction and heat shock signaling.

Dr. Marotta completed his PhD in Experimental Medicine at the University of British Columbia in Vancouver, Canada. His research interests include the identification of new therapeutic targets, investigating their mechanism of action, and the development of diagnostic and companion biomarker assays to personalise clinical disease management.
RA is a chronic autoimmune disease that if left untreated results in severe joint destruction. It is estimated that 30-50% of patients will end up on workplace disability within 5 years of diagnosis. Early identification of RA, assessment of the severity of disease at presentation, together with a prompt and effective treatment strategy can significantly improve a patient's prognosis. To enable all of this, new markers are required 1) to improve the diagnosis of RA; 2) to efficiently stratify patients into different risk categories and 3) to guide treatment decisions.

The 14-3-3 family of proteins are ubiquitously expressed intracellular chaperonins. In 2007, Kilani et al. demonstrated that the eta isoform was abundantly expressed in the synovial fluid and serum of patients with RA. They also demonstrated that there was a significantly strong correlation with the levels of MMPs, and that extracellular 14-3-3η possesses ligand-like activity capable of inducing these degradative enzymes underscoring its role in the pathogenesis of joint damage in RA. Since 14-3-3 eta is not normally present extracellularly, the immune system sees soluble 14-3-3 eta as foreign. Using quantitative assays, we have reported that serum 14-3-3 eta and its auto-antibodies are highly specific RA markers which together identify greater than 90% of early RA patients. Patients who are 14-3-3 eta protein positive have worse disease outcomes over 5 years compared to the patients who are 14-3-3 eta negative. This is likely due to the role that 14-3-3 eta plays in inducing pro-inflammatory factors like TNF alpha that also perpetuate disease. 

Learning Objectives

At the end of the presentation, participants will be able to:

1.    Understand the how markers are used in the management of RA and what are the current needs.
2.    Understand how the two 14-3-3 eta biomarkers assist with the management of RA