Emerging candidate treatment strategies for Hutchinson-Gilford progeria syndrome

Biochem Soc Trans. 2017 Dec 15;45(6):1279-1293. doi: 10.1042/BST20170141. Epub 2017 Nov 10.

Abstract

Hutchinson-Gilford progeria syndrome (HGPS, progeria) is an extremely rare premature aging disorder affecting children, with a disease incidence of ∼1 in 18 million individuals. HGPS is usually caused by a de novo point mutation in exon 11 of the LMNA gene (c.1824C>T, p.G608G), resulting in the increased usage of a cryptic splice site and production of a truncated unprocessed lamin A protein named progerin. Since the genetic cause for HGPS was published in 2003, numerous potential treatment options have rapidly emerged. Strategies to interfere with the post-translational processing of lamin A, to enhance progerin clearance, or directly target the HGPS mutation to reduce the progerin-producing alternative splicing of the LMNA gene have been developed. Here, we give an up-to-date resume of the contributions made by our and other research groups to the growing list of different candidate treatment strategies that have been tested, both in vitro, in vivo in mouse models for HGPS and in clinical trials in HGPS patients.

Keywords: lamin; lamin A/C; nucleus; premature aging; progeria.

Publication types

  • Review

MeSH terms

  • Alternative Splicing
  • Animals
  • Cell Nucleus / metabolism
  • Clinical Trials as Topic
  • Cytoplasm / metabolism
  • Humans
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Mice
  • Point Mutation
  • Progeria / genetics
  • Progeria / therapy*

Substances

  • LMNA protein, human
  • Lamin Type A
  • prelamin A