Background Chronic beryllium disease (CBD or berylliosis) is associated with inhaling beryllium powder or fumes. An exposed person usually gets sensitized to beryllium. Beryllium sensitivity and CBD can develop soon after exposure or later in life. Of those working around beryllium, about 10% get sensitized to it and about half of those will progress to develop CBD.
Sarcoidosis is an inflammatory disease of unknown origin that affects one or more organs in the body. The disease usually begins in the lungs, skin or lymph glands. It is estimated that there are over 25,000 cases diagnosed in the United States each year, with a worldwide incidence varying greatly from 5-40 cases for every 100,000 people.
CBD and sarcoidosis share a common chronic inflammation of the lungs that will progress in the formation of characteristic collections of cells known as granulomas. In more severe cases scarring or fibrosis will occur, reducing the lungs' ability to function.
Therapy for granulomas is aimed at suppressing the stimulated immune response and to improve and/or stabilize lung function. Current therapies include oral corticosteroids as a first line therapy and methotrexate as a steroid-sparing drug in those with more severe cases. Despite corticosteroid and/or methotrexate treatment, many patients worsen clinically overtime, due in part that long term treatment protocols come with significant side effects.
Technology Dr. Day identified sulfasalazine and metabolites of sulfasalazine as potential therapeutics for granulomatous disease such as CBD and Sarcoidosis. 5-ASA is an aminosalicylate that is currently been prescribed for the treatment of granulomatous inflammatory bowel disease, including Crohn’s disease. Initial ex-vivo studies results showed that 5-ASA could suppress up to 50% of the beryllium-induced lymphocyte proliferation and cytokine production in peripheral blood mononuclear cells (PBMCs) from CBD subjects. Dr. Day and his collaborators later conducted the first randomized, double-blind, placebo-controlled trial in the treatment of CBD using 5-ASA to reduce beryllium specific immune response and improve CBD patient’s quality of life. This pilot study resulted in a decline in beryllium specific cytokine production and improvement in clinical outcome and quality of life.
Potential Applications Treatment of CBD and Sarcoidosis.
Brian J. Day, PhD, Jie Huang, MD, Briana Q. Barkes, MPH, May Gillespie, Li Li, MD, PhD, Lisa A. Maier, MD MSPH. 5-Aminosalicylic Acid Modulates the Immune Response in Chronic Beryllium Disease Subjects. - Lung (2018) 196:103–114. PMID: 29080069
Patent Status Issued U.S. Patent #7,498,047, International Patent Pending. Published WO 2007/024741. Other US and International patents pending.
Licensing Status This technology is available for licensing.
For Further Information, Contact: Emmanuel Hilaire, PhD Director Technology Transfer Office National Jewish Health 1400 Jackson St., Room M206b Denver, CO 80206 Voice: 303.398.1262 Fax: 303.270.2352 HilaireE@njhealth.org