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Progeria: Promising results from new gene therapy on animals
Date:10/27/2011

t aimed to slow down the development of the disease, it did not reduce the quantities of progerin. To study this aspect, researchers needed to obtain a relevant animal model.

An "authentic" Progeria model

To generate a model of this kind, Spanish and French researchers decided to introduce a gene mutation (G609G), equivalent to that identified in humans (G608G), in mice to reproduce the exact pathological mechanism found in the children, with a view to then blocking it. The mice models were created under the supervision of Bernard Malissen using the IBISA platform located at the Marseille-Luminy Centre of Immunology . This approach made it possible to obtain young mice that produced progerin, characteristic of the disease in humans. After three weeks alive, the mutated mice displayed growth defects, weight loss caused by bone deformation and cardiovascular and metabolic anomalies mirroring the human phenotype and considerably reducing their lifespan (an average of 103 days compared with two years for wild mice). The progerin thus produced accumulates in mouse cells via genetic mechanisms (abnormal splicing) identical to those observed in humans, i.e. the source of anomalies characteristic of the disease.

for a targeted gene therapy

Using this unique Progeria animal model, the researchers focussed their efforts on implementing a mutation-targeted treatment, with a view to reducing, and, if possible, preventing the production of progerin. To this end, they used "vivo-morpholino" antisense oligonucleotide technology. "This technology, explains Nicolas Lvy, is based on introducing a synthetic antisense aglionecleotide into mice. As is the case with progeria, this sequence is applied to block (or facilitate) the production of a functional protein using a gene. In this case, the production of progerin, as well as lamin A from the gene, were reduced."

There was a highly significant increase in life expectancy
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Contact: Priscille Rivire
presse@inserm.fr
INSERM (Institut national de la sant et de la recherche mdicale)
Source:Eurekalert

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