2024-10-31 06:56:00
What we are is contained in our ADan immense library distributed in 23 pairs of “rooms”, our chromosomes, where the instructions are written in an alphabet of only four letters. In it AD There are more than 6 billion of these letters, information that is copied into every cell of the embryo in a process that is not free from errors. Typically, these errors are irrelevant because they occur in irrelevant areas, but on rare occasions changing a single letter can have dramatic effects. This is the case of progeria, an extremely rare genetic disease that causes premature aging. At the Margarita Salas Biological Research Center, Ignacio Benedicto Español and his team are looking for new ways to treat this disease.
Progeria is extremely rare, affecting approximately 1 in 20 million people. The consequences are dramatic, as the affected person ages rapidly, with an average life expectancy of around 15 years. Recently, the media reported the death of the oldest progeria sufferer, Sammy Basso.
Ignacio Benedicto explains that progeria has its origin in the error of a single letter in a gene known as LMNA. This error produces a faulty protein, called progerin, which accumulates in cells causing serious damage. Progerin affects the structure of the cell nucleus, causing accelerated aging.
In 1998, a child was diagnosed HGPS He promoted research into this disease when his mother, Leslie Gordon, refused to accept that there was no treatment and founded the Progeria Research Foundation. Thanks to these efforts, the role of progerin was discovered in 2003, which allowed the development of animal and cellular models to better study the disease and look for ways to stop it.
Currently, the only drug approved for HGPS It’s lonafarnib. This drug, originally designed to treat cancer, has shown some effectiveness in extending patients’ lives by about four years by reducing the accumulation of progerin in cells. However, this therapy is not a definitive cure and heart failure remains the leading cause of death in people with progeria due to deterioration of blood vessels. To combat this problem, other strategies have been explored, such as cardiac surgery, to which the oldest patient, Sammy Basso, underwent.
Since the problem is a wrong letter in a specific gene, as is the case with progeria, one possible solution is to use gene editing tools to replace the damaged letter with the correct one in the gene. AD of cells. Logically, this is complex to achieve. However, in the laboratories of Harvard University, the University of Oviedo and other pioneering centers, successful gene editing tests were conducted on genetically modified mice affected by the disease, which led to significant improvements in their survival.
Although this treatment is not yet ready to be applied to humans, gene editing technology represents real hope for a permanent cure in the future. To improve the precision of this therapy, explains Ignacio Benedicto during the interview, we are studying which cells would be most useful to treat. A recent discovery shows that reversing the mutation only in vascular smooth muscle cells – an essential component of arteries – can prevent arterial damage and normalize lifespan in mice.
Research on progeria opens the door to understanding the aging processes we all undergo. Ignacio Benedicto and his team focused on studying the vascular endothelial cells (ECs) that line the inside of blood vessels in several tissues severely affected by age-related disorders.
I invite you to listen to Ignacio Benedicto Español, researcher at the Margarita Salas Biological Research Center (CIB–CSIC), Department of Biomedicine, Head of the “Vascular Aging Group”: Visiting scientist in the Cardiovascular Molecular Pathophysiology and Genetics Group at the Carlos National Cardiovascular Research Center III (CNIC)
Further information:
Barettino A, González-Gómez C, Gonzalo P, Andrés-Manzano MJ, Guerrero CR, Espinosa FM, Carmona RM, Blanco Y, Dorado B, Torroja C, Sánchez-Cabo F, Quintas A, Benguría A, Dopazo A, García R , Benedict I, Andrés V. Endothelial Already/TAZ activation promotes atherosclerosis in a mouse model of Hutchinson-Gilford progeria syndrome. J Clin Investing. 2024 October 1:e173448. doi: 10.1172/JCI173448. Epub before print. PMID:39352768.
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Interview between Time.news Editor and Ignacio Benedicto Español
Time.news Editor: Welcome, Ignacio Benedicto Español! It’s a pleasure to have you here to discuss such a fascinating and crucial area of research. Let’s dive right in. You’re studying progeria, a condition that affects roughly 1 in 20 million individuals. Can you explain what progeria is and how it arises at the molecular level?
Ignacio Benedicto Español: Thank you for having me! Progeria, or Hutchinson-Gilford Progeria Syndrome (HGPS), is an extremely rare genetic condition caused by a mutation in the LMNA gene, which provides instructions for making a protein essential for maintaining the integrity of the cell nucleus. Specifically, a single error—a change in one letter of the DNA sequence—leads to the production of progerin, a defective protein that accumulates and disrupts cellular functions, ultimately causing rapid aging and various severe health problems.
Time.news Editor: That’s incredibly insightful. The impact of such a tiny genetic change is mind-boggling. We recently lost Sammy Basso, the oldest known progeria patient. What role did advocates like his mother play in advancing research on progeria?
Ignacio Benedicto Español: Sammy’s story is tragic but also inspiring. His mother, Leslie Gordon, refused to accept the lack of treatment options available at the time. She founded the Progeria Research Foundation, which has been monumental in raising awareness and funding for research. Her advocacy helped scientists discover the role of progerin in 2003, which was a turning point. It enabled us to develop animal and cellular models to study the disease more effectively and seek potential treatments.
Time.news Editor: It’s remarkable how advocacy can fuel scientific progress. Currently, lonafarnib is the only approved drug for progeria. Could you elaborate on its effects and limitations?
Ignacio Benedicto Español: Lonafarnib is indeed a significant step forward; originally intended for cancer treatment, it has shown effectiveness in extending the lifespan of progeria patients by about four years. It works by reducing progerin levels in cells. However, it’s not a cure—patients still face severe cardiovascular issues due to vascular damage, which is often the leading cause of death. As a result, research is ongoing to explore additional therapeutic strategies, including cardiac interventions.
Time.news Editor: Speaking of future possibilities, gene editing is emerging as a potential breakthrough in treating genetic disorders like progeria. Can you share what advancements are being made in this area?
Ignacio Benedicto Español: Absolutely! Gene editing offers a promising pathway to not just manage symptoms but potentially cure genetic disorders. Research at institutions like Harvard and the University of Oviedo has demonstrated that it is possible to reverse the progeria mutation in genetically modified mice, leading to notable improvements in their survival rates. While this approach isn’t ready for human trials yet, we’re investigating the most suitable cells for gene editing. For instance, targeting vascular smooth muscle cells could present a way to prevent arterial damage and significantly extend lifespan.
Time.news Editor: That sounds incredibly hopeful! What do you think are the next steps in making these treatments available to humans?
Ignacio Benedicto Español: The next steps involve refining the gene editing techniques to ensure precision and safety before moving to human trials. We also need to conduct extensive studies to identify which types of cells should be targeted for the most effective outcomes. Collaboration among researchers, ethicists, and regulatory bodies will be essential to navigate the complexities of gene therapy safely.
Time.news Editor: It’s reassuring to hear that progress is being made in such a challenging area. Before we conclude, what message would you like to send to those affected by progeria or families facing similar challenges?
Ignacio Benedicto Español: I want to convey hope. Science is advancing rapidly, and while the road is long and complex, every breakthrough brings us closer to better treatments and potentially cures. The community’s support, including advocacy and funding, plays a vital role in this journey. Together, we can strive for a future where progeria is no longer a life-limiting condition.
Time.news Editor: Thank you, Ignacio, for your insights and dedication to such vital work. It’s been a pleasure discussing these advancements in progeria research with you.
Ignacio Benedicto Español: Thank you for having me. It’s been a pleasure to share this important information.