Five years after the identification of the gene responsible for progeria,
a rare disease causing accelerated and premature ageing, a team of Spanish
and French researchers (Carlos Lopez-Otin and coll. - University of Oviedo -
and Nicolas Levy and coll. - Inserm/AP-HM, Marseille, France) have
successfully demonstrated a treatment for the disease, using mice. This
treatment, combining two existing pharmacological molecules, should slow down
the progression of this disease which has hitherto remained untreatable.
Subject to the authorisation of health agencies, this treatment could
very soon be tested on 15 children in Europe. This represents a major advance
for the families affected by this disease and - more generally - for the
understanding of the normal ageing process.
From identification of the gene to the development of treatment and the
projected clinical protocol, this work - published in the review Nature
Medicine - has received the financial backing of the Association Francaise
contre les Myopathies (Muscular Dystrophy Association) thanks to French
Telethon donations.
The treatment recently validated in mice is based on a combination of two
existing pharmacological molecules: statins (indicated for the treatment and
prevention of atherosclerosis and cardiovascular risks) and
aminobisphosphonates (indicated for the treatment of osteoporosis). The
Franco-Spanish researchers have demonstrated that this treatment attenuated
the effects of the disease and significantly raised life expectancy.
As previously demonstrated by Nicolas Levy's team - which originally
identified the gene in 2003 - progeria is due to the accumulation in the
cells of a truncated protein, progerin, whose toxicity is linked to the
presence of a fatty acid which remains fixed to the protein (whilst it is
eliminated in normal cells). In order to inhibit or block the toxicity of
progerin, the researchers explored the path of synthesis of this fatty acid.
In fact, pharmacological molecules are known to block certain stages in this
path of synthesis.
After several attempts they noted that a combination of a statin and an
aminobisphosphonate could prevent the fixation of the fatty acid to the
progerin, and thus reduce its toxicity. The progerin being less toxic, the
disease develops more slowly.
Following these encouraging results, a clinical protocol based on this
treatment piloted by Nicolas Levy in Marseille (France) is about to start up.
It should last 3 years and will concern 15 of the 25 children affected by
progeria in Europe. The aim of this protocol is to slow down the progression
of the disease and, if possible, prolong the life expectancy - at present
very limited - of the children affected.
Article published in Nature Medicine: click here
Nature Medicine