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CNIC researchers find a possible treatment for one of the main symptoms of premature aging disease
Date:6/17/2013

HGPS is a rare genetic disease that affects one in every 4-8 million births. The disease is caused by a spontaneous mutation in one of the two copies (alleles) of the gene LMNA, which codes for lamin A, a protein important for the integrity and function of the envelope surrounding the cell nucleus. The mutation causes incorrect processing of the messenger RNA for lamin proteins, resulting in the synthesis of an anomalous protein, called progerin.

The new study, published in the leading cardiovascular research journal Circulation, identifies a possible treatment to block the deposition of calcium in arterial wall. This calcification greatly increases the risk of cardiovascular disease, and most progeria patients die of a heart attack or stroke at an average age of just 13 years.

The researchers, led by Dr. Vicente Andrs, director of the Molecular and Genetic Cardiovascular Pathophysiology group at the CNIC, describe the mechanisms that cause vascular calcification in a mouse model of HGPS that recapitulates the main symptoms of the human disease. The study was conducted in close collaboration with the team at the Universidad de Oviedo led by world-leading progeria expert Dr. Carlos Lpez-Otn.

The authors show that the aortas and blood of 'progeric' mice accumulate smaller quantities than healthy mice of extracellular pyrophosphate, a potent inhibitor of vascular calcification. This is due to two main reasons. First, due to a defect in their mitochondria, these mice produce lower amounts of the source of pyrophosphate, ATP. Second, the progeric mice have a higher than normal activity of alkaline phosphatase, the enzyme responsible for degrading pyrophosphate.

Dr. Andrs' team has demonstrated that chronic treatment with pyrophosphate inhibits the deposition of calcium in the arteries of mice with the disease.

The next step toward translating this finding to humans will be to confirm that the same mechanism also exists in children
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Contact: AInhoa Iriberri
airiberri@cnic.es
34-610-295-556
Centro Nacional de Investigaciones Cardiovasculares
Source:Eurekalert

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