Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Endocrine/metabolic disease

a-Antitrypsin (AAT) deficiency

a1-Antitrypsin (AAT; A1AT; SERPINA1); histone deacetylase 7 (HDAC7)

In vitro studies suggest suberoylanilide hydroxamic acid (SAHA) could help treat AAT deficiency. The Z-variant of AAT deficiency is the most severe form of the condition, which involves defective folding, trafficking and secretion of AAT from the endoplasmic reticulum. In human cell lines expressing Z-AAT, HDAC inhibitors including SAHA increased AAT trafficking from the endoplasmic reticulum compared with vehicle. In these cells, small interfering RNA knockdown of HDAC7 increased AAT stability and trafficking compared with silencing of other HDACs. Next steps could include testing SAHA in animal models of AAT deficiency.
At least six companies have therapeutics to treat AAT deficiency in development stages ranging from preclinical to marketed.
Merck & Co. Inc. markets Zolinza SAHA to treat cutaneous T cell lymphoma (CTCL).

SciBX 5(40); doi:10.1038/scibx.2012.1051
Published online Oct. 11, 2012

Patent and licensing status unavailable

Bouchecareilh, M. et al. J. Biol. Chem.; published online Sept. 20, 2012;
doi:10.1074/jbc.M112.404707
Contact: William E. Balch,
The Scripps Research Institute,
La Jolla, Calif.
e-mail:
webalch@scripps.edu