A study of Ecuadorian families with a rare disease known as Lalon syndrome has found that genetic mutations protect them from cardiovascular disease. Researchers believe it is possible to explore drugs and diets that mimic these beneficial effects to combat aging-related diseases such as cancer in the general population.

In 1987, Ecuadorian endocrinologist Jaime Guevara-Aguirre began treating people with Lalon syndrome living in isolated towns in Loja and El Oro provinces in southern Ecuador, near the border with Peru. This disease is characterized by mutations in the growth hormone receptor gene that cause short stature. The height of a person with this condition is no more than 1.5 meters (4 feet 10 inches). The cause is a mutation in a single biochemical letter (G instead of A) in his very long sequence of 3 billion letters that make up the human genome. Intermarriages are common in these communities in Ecuador, which contributes to the prevalence of this syndrome. Even today, residents of these municipalities continue to give birth to children without knowing whether they will be born with Laron. Family photos show the affected parents with their children, who are about 10 years old and already taller than them.

In a conference call from Quito, President Guevara-Aguirre apologized in advance in case communications were disrupted by the power outages plaguing the country, which has been mired in a spiral of violence and instability. “In 1987, it would take us two days to get to these towns in my father’s four-wheel drive, and we would have to walk another two to three hours to get to some towns. It was a very remote area. But the patients were fascinating,” says Guevara-Aguirre of the University of San Francisco de Quito. Since then, he has diagnosed about 100 affected people, about a third of the world’s known cases.

After 20 years of follow-up, doctors observed a mysterious pattern. Cancer and diabetes were rare in Lalon’s career, but their seemingly healthy relatives suffered from these diseases with the same frequency as other Ecuadorians. Doctors claimed that Laron’s mutation protects against diseases associated with aging. The problem caught the attention of biochemist Valter Longo, a researcher at the University of Southern California who was focused on finding diets that could thwart chronic disease.

In 2011, researchers showed that people affected by Laron produced less IGF-1, a protein essential for childhood growth. IGF-1 also promotes uncontrolled proliferation of cancer cells in adults. In laboratory studies, mice with lower levels of this protein live up to 40% longer, develop fewer tumors, and appear smaller than normal.

In 2017, the two researchers published another study indicating that this mutation also protects against neurodegenerative diseases. Although few affected individuals live past the age of 80, there were no cases of Alzheimer’s disease or dementia among the patients identified. While many of their relatives without the mutation suffered and died from diseases related to aging, those affected by the syndrome died mainly from accidents and alcoholism, making it very common in these Andean communities. It is.

Researchers claim in a new study that the Laron mutation has a protective effect against cardiovascular disease. They studied 21 men with the syndrome and 23 unaffected relatives. Carriers had lower blood sugar and blood pressure. The study, published in a journal, found that even though they had high levels of “bad” LDL cholesterol, they had far less atherosclerotic plaque. and.

“This is the most important of all the studies,” Longo emphasizes. “Skeptics had argued that heart disease was the most common cause of death in these people, but we showed that this was not the case.”Many of the patients in the study They are overweight or obese, consume a lot of tobacco and alcohol, and lead a poor lifestyle. “The worst thing is that some people think they can do whatever they want because they’re protected, but that’s clearly not the case,” said Italy, who has “visited these Ecuadorian villages dozens of times.” emphasizes the American biochemist. times. ”

Dr. Longo emphasized that the fasting-mimicking diet he devised reduces circulating IGF-1 levels, which is likely responsible for the beneficial effects observed in both animals and Laron patients. ing. Another author of the paper, John Kopcik of Ohio University, said that some molecules that block growth hormone receptors can slow tumor progression in mouse and human breast cancer cells, making conventional treatments less effective. showed improvement. One of these molecules is pegvisomant. It is manufactured by the multinational company Pfizer and has already been approved as a treatment for acromegaly, a hormonal imbalance that causes excessive growth of the face and limbs.

Israeli doctor Zvi Lalon discovered the syndrome in 1966 in a consanguineous Jewish family from Yemen. A 2013 genetic study suggested that the mutation probably originated with Spanish and Portuguese Sephardic Jews who fled the Inquisition in the 15th century and founded small communities in Ecuador, Chile, and Brazil. There are 17 different mutations that cause Laron syndrome, and one of them has reached the United States, explains the scientist, professor emeritus at Tel Aviv University. In recent years, he has published several studies focused on how to replicate the cancer prevention effects seen in these patients. The scientist believes that the results seen in Ecuador cannot be generalized. “In our cohort of 76 people followed over many years, we found that the majority of older, obese patients developed insulin resistance, with three men and eight women having diabetes. ‘But only one of them has the same mutation. Ecuadorian, he said. His next scientific goal is to calculate how many people around the world actually suffer from this condition. “There are probably more than 500 people and they are undiagnosed in many countries,” he said by phone from Tel Aviv.

Laron syndrome is a recessive trait. This means that to have Laron syndrome, he must inherit two copies of the mutated gene. One from the father and one from the mother. It is possible for one of her girlfriends with this syndrome to have a healthy child, but it is also possible for her two without the syndrome to carry the mutation and give birth to Laron’s child. Guevara-Aguirre admitted it was “a genetic lottery” amplified by inbreeding.

This doctor showed that dwarfism can be treated by administering recombinant IGF-1 protein from an early age. Additionally, since 1992, he has been trying to establish a “large-scale” genetic diagnostic system that would allow these residents to find out whether their partner is a carrier of the mutation, which It hasn’t happened yet. “This is an easy and cheap intervention, but it’s not happening because of ignorance on the part of the authorities,” he says.

Guevara-Aguirre’s current goal is to determine whether mutation carriers live longer than their siblings or other relatives. “My feeling is yes, but it has to be proven. The problem is that this area is controlled by drug guerrillas,” he laments.

Alejandro Martín Montalvo, a researcher at Spain’s National Research Council, collaborated with Longo and Guevara Aguirre on a study on Lalon and cancer in 2011. He thinks: As previously believed, heart failure can occur. Furthermore, it opens up new areas of research on how to transfer these benefits to the public. ”

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