Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Exploring new therapeutic strategies in Hutchinson-Gilford progeria syndrome preclinical models

Project Coordinator

Fundación Centro nacional de Investigaciones Cardiovasculares Carlos III


David Filgueiras Fundación Investigación Biomédica Hospital Clínico San Carlos Madrid, Spain
Karima Djabali School of Medicine, Technical University of Munich Garching , Germany
Ryszard Rzepecki University of Wroclaw Wroclaw, Poland
Giovanna Lattanzi CNR Institute of Molecular Genetics Bologna, Italy

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease (prevalence: 1 in 20 million) characterized by multiorgan defects, accelerated aging, and death at an average age of 14.6 years mainly from myocardial infarction or stroke. It is caused by a heterozygous de novo point mutation in the LMNA gene leading to the synthesis of progerin, a permanently farnesylated prelamin A mutant protein. HGPS has no cure and clinical trials targeting progerin farnesylation showed increased mean survival of only ~1.6 years in treated patients. It is therefore urgent to develop new strategies to treat or cure HGPS.
TREAT-HGPS is a transnational 3-year program involving scientists from 4 European nations who will exploit existing HGPS cell and mouse models to: a) discover novel combinations of therapeutic drugs to fight HGPS, and b) provide essential new knowledge about reversibility of progerin-induced damage.
1) Evaluate whether combinations of available drugs known to target either progerin (rapamycin, all-trans-retinoic acid, sulforaphane, trichostatin A) or progerin-induced effects (anti-IL6r antibodies) can synergize to ameliorate disease symptoms in cell and mouse models of HGPS. RNA interference strategies will be also tested.
2) Assess whether systemic progerin suppression at different time-points in the lifespan of progeroid mice reverses HGPS progression to ascertain the potential benefit of future approaches targeting progerin expression.
3) Evaluate whether progerin suppression restricted to vascular smooth muscle cells, main target of progerin, provokes overall beneficial effects in progeroid mice as an alternative approach to more challenging systemic progerin suppression.

E-Rare 2012 - Created by Toussaint Biger