NexDx Co-Founder Gary S. Firestein Publishes Findings that Epigenetics Alters Genes in Rheumatoid Arthritis

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The scientific discoveries that led to the founding of the science driven molecular diagnostics company NexDx, Inc. ( in 2011 in San Diego are published in the current online edition of the Annals of the Rheumatic Diseases (

The scientific discoveries that led to the founding of the science driven molecular diagnostics company NexDx, Inc. ( in 2011 in San Diego are published in the current online edition of the Annals of the Rheumatic Diseases (, one of the highest impact peer reviewed scientific and medical journals, with the highest Impact Factor in the rheumatology category.

The new research, conducted by Gary S. Firestein, M.D., and colleagues at University of California at San Diego, is the first study to uncover a striking pattern of aberrant modifications in the DNA of the inflammation-producing cells, referred to as fibroblast-like synoviocytes (FLS), lining the joints of patients with rheumatoid arthritis (RA).

The DNA modifications that Dr. Firestein’s lab discovered in RA patients’ cells are caused by an epigenetic mechanism known as methylation. Epigenetics refers to the modifications to an individual’s unique DNA that influence the expression, or activity, of his/her genes without altering the order or sequence of the original DNA.

Dr. Firestein, an internationally recognized rheumatologist and Professor in the Division of Rheumatology, Allergy and Immunology at UC San Diego School of Medicine, and his team identified and then compared the DNA methylation profiles of the FLS of patients with RA, individuals with osteoarthritis (OA), which unlike RA is not an inflammatory or autoimmune disease, and individuals not affected by either disease.

RA’s DNA methylation pattern was found to be novel and to involve 207 genes, many of which play key roles in inflammation, regulation of the matrix that supports cells, and recruitment of leukocytes, which are key cells of the immune system.

Dr. Firestein and his colleagues also determined that a gene’s methylation state – whether it was hypo or hyper-methylated – correlated with its actual expression or activity in RA cells.

“The DNA modifications that are unique to RA are potential biomarkers for a blood-based test to diagnose the disease early when it can be most effectively treated,” said Jonathan Lim, M.D., chairman and CEO of NexDx.

Drs. Lim and Firestein co-founded NexDx in August 2011. In April 2012, NexDx announced that it had signed an exclusive worldwide license agreement with UC San Diego to develop and commercialize Dr. Firestein’s discoveries.

In addition to developing a diagnostic test, NexDx is investigating the aberrant DNA methylation signatures to determine the optimal therapy and discover novel drug targets for biopharmaceutical company partners.

Additional contributors include Kazuhisa Nakano and David L Boyle, UCSD Department of Medicine; and John W Whitaker and Wei Wang, UCSD Department of Chemistry and Biochemistry.

LINK to UC San Diego news release about the paper:

NexDx, Inc., located in San Diego, California, is a science driven molecular diagnostics company providing next generation products and services for personalized medicine in rheumatoid arthritis and other autoimmune diseases.

The company, founded in August 2011 by Jonathan E. Lim, M.D. and Gary S. Firestein, M.D. (Professor of Medicine at UC San Diego), is a pioneer in the application of epigenomics and other next generation molecular approaches to the discovery, development, and commercialization of novel biomarkers and tests for diagnostic and therapeutic applications in autoimmune diseases.

On June 29, NexDx announced the successful closing of a $2.1 million Series B financing led by City Hill Ventures, LLC ( and a $500,000 capital term loan from Silicon Valley Bank (


RA, which typically strikes between the ages of 30 and 50 years but also can afflict children, is the most common chronic inflammatory joint disease with an estimated incidence of about 1 to 2% of the U.S. population, and a 2 to 3 times higher prevalence in women than in men. The overall costs associated with RA are estimated to exceed $30 billion annually in the U.S.

Unlike osteoarthritis, RA is a systemic disease in which the body's immune defense system attacks the thin layer of cells called the synovium that lines each joint. This abnormal immune response generates proteins that inflame body tissues and further damages cartilage and bone. The swollen joints and crippling stiffness, particularly of the hands and feet, can be painful as well as debilitating. In RA, the immune system can also damage the heart, lungs and membranes that surround these organs.

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Cathy Yarbrough
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