An overview of treatment strategies for Hutchinson-Gilford Progeria syndrome

Nucleus. 2018 Jan 1;9(1):246-257. doi: 10.1080/19491034.2018.1460045.

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is a sporadic, autosomal dominant disorder characterized by premature and accelerated aging symptoms leading to death at the mean age of 14.6 years usually due to cardiovascular complications. HGPS is caused by a de novo point mutation in the LMNA gene encoding the intermediate filament proteins lamins A and C which are structural components of the nuclear lamina. This mutation leads to the production of a truncated toxic form of lamin A, issued from aberrant splicing and called progerin. Progerin accumulates in HGPS cells' nuclei and is a hallmark of the disease. Small amounts of progerin are also produced during normal aging. HGPS cells and animal preclinical models have provided insights into the molecular and cellular pathways that underlie the disease and have also highlighted possible mechanisms involved in normal aging. This review reports recent medical advances and treatment approaches for patients affected with HGPS.

Keywords: AON; FTI; HGPS; MG132; Metformin; Progerin; Rapamycin; ZOPRA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / drug effects
  • Cell Nucleus / genetics
  • Cell Nucleus / pathology
  • Humans
  • Mutation
  • Progeria / drug therapy*
  • Progeria / genetics
  • Progeria / pathology

Grant support

This work was supported by grants from Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille University, A*Midex Foundation (VinTAGE Program) and the Association Française contre les Myopathies (AFM grant MNH-Decrypt 2011–2015 and TRIM-RD 2016–2020 to NL). This study is part of the FHU A*MIDEX project MARCHE n.ANR-11-IDEX-001-02 funded by the “Investissement d'avenir” French governmental program, managed by the French National Research Agency (ANR).