New approaches to progeria.
Progeria (Hutchinson-Gilford progeria syndrome) is a rare genetic disorder that offers considerable insight into the biology of premature aging. This review summarizes the clinical characteristics of this disease and the underlying mutation in the lamin A (LMNA) gene that results in this phenotype. Modifications in the processing of prelamin A through alterations in farnesylation are detailed, because this pathway offers a possible drug target. Finally, discussion of an ongoing clinical trial for these children, including possible parameters for evaluation, are discussed. In the span of less than a decade, this disease has progressed from an interesting phenotype to one in which the gene defect has been identified, animal models have been created and tested with drugs that target the primary disease pathway, and significant clinical baseline data for the support of a clinical trial have been obtained.
Kieran
Mark W
MW
Dana-Farber Cancer Institute, Department of Pediatric Oncology, 44 Binney St, Boston, MA 02115, USA. mark_kieran@dfci.harvard.edu
Gordon
Leslie
L
Kleinman
Monica
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D009154:Mutation; D011371:Progeria / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004791:Enzyme Inhibitors; D034904:Lamin Type A; D019883:Alkyl and Aryl Transferases