Stopping RA before it starts

Research partnership seeks high-value biomarkers and diagnostic test for rheumatoid arthritis

Jim Cirigliano
LEIDEN, The Netherlands—Ignyta Inc. has entered into acollaboration agreement with Leiden University Medical Center (LUMC) focused onearly synovitis and rheumatoid arthritis (RA). The collaboration will center onepigenetic analysis to identify high-value biomarkers associated with RA, withthe ultimate goal of generating new diagnostic tests to identify patients withRA at an early stage in the disease.
 
 
The partnership pairs Ignyta's platform for performingepigenetic analysis with LUMC's global reach and vast patient base. The desiredoutcome is the discovery of high-value biomarkers associated with RA, in hopesof moving toward diagnostic tests and customizable, personalized patient care.LUMC has a reputation as a preeminent RA treatment provider in the world, alongwith incredibly valuable longitudinal data gained from long-term care of RApatients. Ignyta's team has a long history of developing and commercializingnovel biomarkers and tests for diagnostic and therapeutic applications inautoimmune diseases, with a particular focus on RA and lupus. 
 
The researchers will perform comprehensive epigeneticanalysis to identify phenotypes of interest associated with RA versus controls.Complex though it may be, epigenetic analysis is necessary because geneticsalone fail to explain a person's predisposition for developing the disease.
 
 
"In pairs of fraternal twins—who share the same DNA—if onedevelops RA, the chance the other also develops the disease is only 15percent," says Zachary Hornby, vice president of corporate development atIgnyta.
 
 
Clearly, environmental factors and other influences beyondgenetics alone play a significant role in the development of RA.
 
"There are a growing number of suspected risk factors," saysDr. Annette H.M. van der Helm, an internist and rheumatologist at LUMC. "Theinformation changes all the time."
The research will attempt to identify DNA methylationpatterns, in the hopes of identifying a signature that could become adiagnostic tool with both high specificity and high sensitivity for earlydetection of RA. 
 
Early detection and treatment for patients with RA iscritical for improved quality of life. Currently, however, there is nodefinitively diagnostic test for the disease.
 
 
"The later the patient begins receiving treatment, thehigher the rate at which the disease becomes chronic," says van der Helm.
 
 
The current method of diagnosis relies on a clinicaldiagnosis, whereby the patient's physician diagnoses the disease based onsubjective scoring across multiple symptom criteria. Unfortunately, this methodof diagnosis is far from perfect, and typically means that symptoms must berelatively advanced before a physician can confidently diagnose a patient withRA versus other diseases with similar symptoms.
 
 
"The goal is to move toward an objective, definitive testthat could identify RA patients early in the disease progression," says Hornby.
 
After relevant markers are positively identified, there is agreat deal of promise in the potential for manipulating gene expression toimpact the severity or the course of the disease. 
 
"By comparing outcomes of RA patients with genomicmanipulation, we're opening a new field, a new area of study, and it'sintriguing to see what the outcomes will be," says van der Helm. "It'spotentially very promising."
 
 
The LUMC, located in the Netherlands, employs 7,000 peopleand is one of the premier rheumatology clinics in the world. It sees a largenumber of RA cases from around the globe, often beginning very early in thedisease progression, making it uniquely positioned to follow the care of thesepatients longitudinally. A considerable portion of LUMC's research centers onthe translation from fundamental research to its use in patient care. Asidefrom RA care, LUMC also offers an array of other high-level clinical care includingorgan transplants, cardiovascular interventions and all types of bone marrowtransplants.
 
Ignyta is a personalized medicine company located in SanDiego that develops new products and services to customize diagnosis andtreatment of patients with RA, lupus and other autoimmune diseases. The companywas launched in August 2011, and specializes in the application of 'omicstechnologies integrated with bioinformatics to the development andcommercialization of novel biomarkers and tests for diagnostic and therapeuticapplications in autoimmune diseases. In 2012, the company successfully closed a$5.5 million Series B financing led by City Hill Ventures LLC and ColtVentures, and a $500,000 capital term loan from Silicon Valley Bank.
 
 
 

Jim Cirigliano

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