Cancer drugs offer new hope for Crohn”s disease and sarcoidosis

A new study offers insight into a new treatment avenue for two painful inflammatory diseases: Crohn”s sisease and sarcoidosis.

While the loss of NOD2 increases the risk of developing Crohn”s disease, increased activity of this gene is also thought to exacerbate symptoms.

Additionally, activating NOD2 mutations can cause genetic sarcoidosis – an inflammatory disease affecting multiple organs in the body, but primarily the lungs and lymphoid tissue.

A Case Western Reserve University School of Medicine research team has identified two existing FDA-approved drugs that are able to inhibit the activity of NOD2”s binding partner, the kinase RIP2, and therefore, also inhibit the activity of NOD2.

By inhibiting NOD2”s signaling pathways through the use of medications, patients with these diseases potentially have a new avenue of treatment.

Over the past decade, drugs targeting protein kinases have been among the most successful pharmacologic agents developed in the treatment of both solid and blood-based cancers.

Two of these medications, Tarceva and Iressa, target the cancer cells” epidermal growth factor receptor (EGF-Receptor) protein kinase to inhibit the growth of both lung cancer and brain cancer.

At Case Western Reserve, Drs. Justine Tigno-Aranjuez and Derek Abbott screened known tyronsine kinase inhibitors and found that these two drugs are very potent against RIP2. The researchers discovered that the medications target RIP2 as efficiently as they target the EGF-Receptor.

The study further shows that both Tarceva and Iressa both inhibited and diminished the effects of NOD2 hyperactivation.

A difficult step in drug development centers on demonstrating the safety and efficacy of a new drug and ultimately having that drug approved by regulatory agencies. Tarceva and Iressa have been through the clinical regulatory process and have attained FDA approval.

Therefore, this opens a door for treatment that, with appropriate preclinical testing for this new function, could be more rapidly translated into clinical treatment. Although preliminary, this work suggests that these FDA-approved drugs may benefit conditions exacerbated by NOD2 hyperactivation, including sarcoidosis.

The study appears in the December 1st issue of Genes and Development.