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Arsenical Compounds as Therapeutics for Inflammatory Diseases

Posted Jul 24 2013 8:00pm

Description of Invention:
FDA approved Arsenic trioxide (Trisenox or As2O3) and other arsenical compounds for treatment of acute inflammatory conditions have been shown to be anti-inflammasome therapies. Inflammasomes are large cytoplasmic multi-protein complexes that form in response to intracellular danger signals and play a key role in many infections by controlling the innate immune response. Inflammasome activation has been implicated in metabolic disorders, such as diabetes, and inflammatory diseases, such as gout, arthritis, and cholesterol-associated atherosclerosis. The technology relates to arsenical compounds that inhibit a number of inflammasomes, including the Nlrpl, Nlrp3 and Naip5/Nlrc4, primarily by acting as an inhibitor of caspase-1 activity in innate immune cells (macrophages). It was shown that arsenical compounds induce a cellular condition which inhibits both the autoproteolytic activity of caspase-1, as well as its ability to cleave cytokine substrates. Further, it was shown that the inhibition does not occur through direct modification or inhibition of the caspase-1 enzyme, but rather through induction of a cellular environment inhibitory to its activity. Efficacy in inhibiting immune cell recruitment in a mouse model of gout has been demonstrated. The arsenicals have potential as treatment for a variety of inflammatory conditions.

Applications:
Therapeutics for rheumatoid arthritis, gout, colitis and various inflammatory skin diseases.

Advantages:
These FDA-approved compounds have potential off-target use for treatment of acute inflammatory conditions shown to be responsive to anti-inflammasome therapies.

Development Status:
  • Early-stage
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Inventors:
Mahtab Moayeri (NIAID)
Nolan K Maier (NIAID)
Stephen H Leppla (NIAID)


Patent Status:
HHS, Reference No. E-112-2013/0
US, Application No. 61/784,138 filed 14 Mar 2013



For Licensing Information Please Contact:
Suryanarayana Vepa Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: vepas@mail.nih.gov
Phone: 301-435-5020
Fax: 301-402-0220


Ref No: 2593

Updated: 07/2013

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