Metformin, a common anti-diabetic drug, is thought to be able to treat progeria. This very rare genetic disease causes premature aging in children.
Their skin is wrinkled, their hair is falling out and joint pain is everywhere. And yet, these patients are less than 12 years old. This premature aging is due to a very rare genetic disease, progeria. The mutation that causes it considerably shortens life expectancy: patients rarely exceed the age of 13. An Inserm team, in conjunction with the AFM-Telethon, may have found a way to slow down this accelerated decline. It resides in a very common drug, an oral diabetes medicine known as metformin. The discovery is described in Aging and Mechanisms of Disease, a review of the group Nature.
Target production
Curing “old children” is a puzzle that more than one scientist is tearing their hair out of. The solution, presented by the French team, nevertheless seems simple. But it wasn’t until 2012 that the idea emerged, after the publication of a study on the genetic impact of metformin. Because progeria is a disease caused by a specific genetic mutation: it occurs on the LMNA gene. “The gene normally codes for laminated proteins A and C,” explains Inserm. They ensure the integrity of cell nuclei.
In the case of Hutchinson-Gilford syndrome, the other name for progeria, the protein expressed is not complete, and above all toxic. It deforms the nucleus of cells and causes premature aging. It is not normally present in the body until the age of 50 or 60. “Today, the drugs being tested on these patients are aimed either at destroying progerin or at blocking its toxicity, but none of them has an effect on its production,” explains Dr. Xavier Nissan. . This is what we sought to identify in this study. “
Reduction of toxic proteins
Progeria is extremely rare: only three cases are known in France, 25 on the European continent. The disease affects one in 4 to 8 million births, according to Inserm. Developing a new drug could therefore prove to be unprofitable. Instead, the signatories of this study reviewed already existing molecules. Metformin emerged as a particularly interesting avenue: this anti-diabetic regulates the expression of several hundred genes.
It remained to verify that the drug was effective against the disease. The researchers therefore used cells taken from patients with Hutchinson-Gilford syndrome. “For this, we used the reprogramming technique to return patients’ cells to the stem state. Once rejuvenated, these stem cells (or iPS) were transformed into skin, bone or blood vessel cells, ”explains Xavier Nissan. A low dose of metformin was applied to them.
The anti-diabetic is indeed effective. It inhibits the protein which participates in the expression of progerin up to 40%. Better still: the presence of progerin in cells is reduced by up to 50%. The deformation of the nuclei is no longer observed. For Professor Nicolas Levy, who also signs this work, this is undoubtedly good news. “These results suggest a new therapeutic approach, alone or in combination with other molecules, for the treatment of progeria, the benefit of which will now have to be evaluated in animal models of this syndrome. “
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