Treatment of Progeria with Farnesylation Inhibitors

Treatment of Progeria with Farnesylation Inhibitors

Hutchinson-Gilford Progeria Syndrome (HGPS) is a genetic disorder characterized by premature aging and the affected children die of myocardial infarction or cerebrovascular accidents at a young age of around thirteen years. HGPS is caused by a single gene mutation in the LMNA gene encoding for lamin A/C, component of nuclear lamina. This deletion mutation causes accumulation of an abnormal protein known as progerin. Progerin which is improperly farnesylated and truncated leads to abnormal nuclear scaffolding. Hence farnesyl transferase inhibitors have been used in the treatment of progeria. In a study published in the Circulation [1] farnesylation inhibitors increased the survival by about 1.6 years compared to the usual survival of around fourteen and a half years.

Reference

1. Leslie B Gordon, Joe Massaro, Ralph B D’Agostino Sr, Susan E Campbell, Joan Brazier, W Ted Brown, Monica E Kleinman, Mark W Kieran, Progeria Clinical Trials Collaborative. Impact of Farnesylation Inhibitors on Survival in Hutchinson-Gilford Progeria Syndrome. Circulation. 2014 Jul 1;130(1):27-34.