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Pharmaceuticals

Low Doses Of Lymphoma Drug Vorinostat Prevent Diabetes In Mice

Medication blocks removal of acetyl groups on lysine residues, but more safety studies are needed

by Carmen Drahl
January 13, 2014 | A version of this story appeared in Volume 92, Issue 2

Acetyl groups on lysine residues are chemical master switches that control myriad activities in cells. Acetylation is best known for its involvement in gene transcription and cancer progression. In fact, FDA in 2006 approved vorinostat, a molecule that blocks the removal of acetyl groups from lysine residues, to treat a type of lymphoma. Acetylation also influences inflammation, so researchers are investigating whether vorinostat and similar drugs could treat autoimmune diseases such as type 1 diabetes. Now, a multi-institution team has reduced the occurrence of type 1 diabetes in mice by feeding them vorinostat or another lysine deacetylase inhibitor, givinostat (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/pnas.1320850111). The researchers, led by Thomas Mandrup-Poulsen of the University of Copenhagen, also learned that the compounds delay the mice’s onset of diabetes. The effective doses were two orders of magnitude lower than those given for cancer treatment, Mandrup-Poulsen says. The drugs can be taken orally, so patients may be more likely to follow that regimen compared with insulin injections. The authors think this study lays some groundwork for clinical trials in type 1 diabetes patients, but they call for more safety studies on vorinostat first.

The top structure is verinostat; the bottom structure is givinostat.

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