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In Tlaltetela, a small town in the region of the high mountains of Veracruz, dedicated to the cultivation of sugar cane, coffee and Persian lemon, whose vegetation seems to touch the sky, many of its residents inherit small plots of land for cultivation and, among other things, deadly Illness. The one Leticia Melchor predicted so many times. “Person to stare at, person to get sick. Aren’t you a witch?” her husband asked her one day as she stood in the middle of the street and looked at a neighbor’s. “What’s happening is that I can tell by looking at it before the first symptoms appear. I was too close to her and that cursed woman won’t betray me anymore,” Melchor affirms, without giving her name.
The woman is referring to Spinocerebellar Ataxia 7, a neurodegenerative disease that attacks the brain, paralyzing the body and causing sudden blindness. “It’s the worst word there can be: stop looking and stop walking; sheer agony “He makes me bring piñatas to my grave when they should be on the patio of our house,” reveals Melchor, who lost his seven-year-old daughter, Yendy, two years after his younger sister contracted the same disease. . Her husband, her mother-in-law, her brother-in-law, her little nephew and maybe also her father, who is showing the first signs, also suffer from this disease.
Your family is not alone. Many residents of Tlaltetela suffer from this disease. In fact, it is the community “with the highest caseload in the world,” according to Jonathan Magaña, a molecular biologist who specializes in this highly debilitating disease. Ataxia affects the motor system and leads to loss of vision, difficulty speaking and eating, loss of balance and body control. In addition, he can weaken the musculature to the point where he prostrate his victims, first in a wheelchair, then in bed, until finally he manages to breathe his last.
Known as SCA7, this type of ataxia is a rare disease and cannot be cured. “That’s why I prefer to call her an orphan,” says the researcher, who came to the community to study her more than a decade ago when told she lives in a marginalized region in the middle of the Sierra Madre Oriental mountain range of Veracruz , at an hour and Xalapa average, “the numbers affected were scandalous.”
Leticia Melchor Calte watches her daughter Yendi García Melchor’s room. Nayeli Cruz
“It seems like this disease has decided to take root here,” Melchor says, referring to the condition that causes a reckless mutation in the ataxin-7 gene, ATXN7. This change in DNA sequence creates a whimsical protein that causes cells in the cerebellum and macula, the light-sensitive tissue of the retina, to degenerate. And that it’s an autosomal dominant inheritance: it only needs to be present in one of the chromosomes that make up the pair for the disease to be transmitted. “If the carrier parent has one healthy allele and one mutant allele, there is a 50 percent chance of transmitting the disease,” explains the biologist. “It’s like a turning point: the face has the healthy version, the cross has the mutation. And in this region of Veracruz, the likelihood of that happening is very high,” he explains.
At least 200 affected in a town of 6,000 people
If the incidence of this disease at a global level is less than one person per 100,000, in the municipality of Tlaltetela, which has fewer than 6,000 inhabitants, there are more than 200 affected. “And they represent just the tip of the iceberg. The real cases are much more. Many people have no symptoms yet and live with it without even knowing it. People die without a diagnosis, but they pass the disease on to their offspring,” says Magaña.
When the scientist first visited this mountainous town, reached by a road winding through green valleys and sprawling orchards, “the disease was taboo, nobody wanted to talk about it,” he says. It was Genes Latinoamérica, a foundation that has been providing food, medicine and many other needs of a population forgotten by those in power for a few years, that made it possible to connect the community with the doctors. “After a while, we managed to get closer to the families and get to know the disorder better,” says the biologist.
An old acquaintance in Tlaltetela, ataxia has afflicted its residents for generations, but until recently it was considered a curse rather than a disease. “Many people thought it was contagious and could be transmitted through contaminated water. The symptoms were also confused with age, as they appeared in older people and were not as aggressive as they are today,” explains Andrea Moctezuma, a social anthropologist specializing in disability and human rights.
“But the disease started appearing in younger people, 40 years old,” explains the researcher, focusing on the situation in the community where the mutation is becoming more widespread and aggressive every day. “The alarm sounded when it appeared in very young children, barely 5 years old. And he takes them very quickly,” he says.
Andrea Zapata Morales and her father Andrés Zapata Rebolledo rest at their home. Nayeli Cruz
“My daughter was dead in life”
Three months after the death of her sister Abril, at the age of 12, Yendy’s symptoms began, then five years old. “She left us when she was two and a half years old. And on the same day of the funeral, I warned my husband that we were about to bury another child,” Melchor recalls. That day, at his daughter’s funeral service, I noticed “the sickness in my nephew Edgar’s small appearance,” he says.
Since then, the little boy’s ataxia has progressed significantly. “He has lost his balance and can no longer hold himself, he can no longer walk, although he can still see something,” says Moi García Prado, the father who runs a bakery. He also has the disease. And his mother and his brother who is Melchor’s husband. “But for us, the symptoms progress slowly. The larger the disease occurs, the slower it attacks. The little one is moving very quickly,” says García Prado, without taking his eyes off his wide-eyed little son lost in infinity. “The eldest, 17, went to the US, it seems he didn’t inherit it,” says the father with relief in his voice.
Until ten years ago, ataxia never occurred in the Tlaltetela child population. “But over the generations, the mutation repeated itself more and more frequently and the disease multiplied. “The larger the mutation, the more defective parts the gene carries, the earlier the disease appears and the more aggressive it is,” explains Magaña.
Melchor shows a photo album in which Yendy appears: The first shows the girl at her christening. In the following images, she appears dressed as Jarocha, riding a bicycle and embracing her father at the end of kindergarten; in another, loud at a party. “You see, the illness is already making itself felt here, he no longer looks up,” says the mother. Later, she was gradually deterred by the disease: “At first she found it difficult to jump, then she kept falling, at the age of six months she went blind, she could no longer eat because she was choking, and she lost her little cheeks.” she remembers.
No one knows the stages of ataxia better than she does, and how she traces children’s faces and bodies until they all look the same. “The eyes widen, the face lengthens, the cheeks sag, the little hands stiffen, the little looks disappear,” he recites from memory, never taking his eyes off the photos, an instant placebo to the pain of absence. The girl is no longer there, but her memory permeates the whole house, which lives on bread and growing lemons. In the parents’ room, the soft toys still stand out from the huacales, from the closets the pink blankets that are the same color as the walls of the house and the details that adorn the altar with the portraits of the little girl and many bouquets of flowers . Also, the print on the blouse Melchor is wearing is pink because “that was the girl’s favorite color.”
Melanie Hernández plays with her sister Marely.Nayeli Cruz
The last photos of the girl are from the last birthday. She appears in a princess dress in her mother’s arms. “My daughter was dead in life and I only realized it when I saw the photos later. “Yendy was in terrible agony for 17 days,” he recalls. “And cases of up to four months have been recorded,” says Moctezuma. “SCA7 is terrible, causing a lot of disability and a lot of stigma. But above all it is a disease of losses. Those who suffer from it even lose their identity,” emphasizes the anthropologist.
“This disease takes away everything but clarity,” says Juan Medina, 56. He developed ataxia more than 30 years ago. In adults, the disease progresses much more slowly than in children, but causes a state of intoxication that causes them to lose balance and occasionally trip over their faces. What is known as drunkenness syndrome. “They believe they are drunk and will not let them on the transport or ban them from public places. That’s why they isolate themselves and don’t want to leave their homes anymore,” says Moctezuma.
“Once they left me in front of the bank door because they thought I was drunk. The thing is that you feel exactly that, it makes you dizzy,” says Medina. The disease came to him with the loss of balance. Then his vision became impaired. “One eye still works, the other is almost nothing,” he says as he slowly walks through his home’s backyard, where coffee plants, bananas, and lemon trees sprout, but also chili peppers, chayote, and the massive stalks of sugar cane. de azúcar: a small orchard with the best in town in the mountains. But the man who trudges through the undergrowth will soon no longer see her.
Farmers who cannot earn a living
“Men are the ones who have the greatest resistance to ataxia. It greatly affects masculinity because they are providers and this disease causes economic and family reconfiguration. The majority of farmers cannot earn a living,” clarifies anthropologist Moctezuma. Medina is grateful that he can still cultivate his land and feed his family. Their 33-year-old daughter, Elizabeth, is already completely blind and confined to a wheelchair. “Her husband distanced himself from her when the first symptoms started and my wife and I took her home with the grandchildren. “The girls are healthy, only the boy seems to have inherited the disease,” says the farmer. Yosué, 11 years old, is becoming drastically blind and the child occasionally falls. “It almost always puts me in a bad mood and yells at all of us,” says the grandfather.
The way ataxia sufferers lose their bodies leads to anger, frustration, depression, anxiety and a great deal of guilt. “The day we gave Yendy the diagnosis, my husband also got sick, but he never wanted to get the piece of paper. The burden is being thrown because the mutation is coming from him,” says Melchor.
Juan Medina meets his family in the dining room of his home. Nayeli Cruz
“It’s like the guilt you carry around is very big. My daughter and grandson are sick and will die. That responsibility is on my roof,” Medina says as he stacks the ripest lemons.
The origin of a mutant lineage
Producer of lemons and progenitor of the seed of evil, it was said by his family until recently. “People talk a lot and can be very vicious. But they are somewhat right: we are marked wherever we go. “In the end, my last name is a death sentence,” the farmer complains. Like the Medina Melchor, the Rosales or the Prado also have the cursed mutation Magaña and his team of geneticists reconstructed the history of the disease in Tlaltetela, where the men are farmers or migrate to the United States to find work..
“First we identified the families and then created a family tree,” says the researcher. After eight generations, he reached the first person in the region to show the symptoms, “we’re talking about the early 19th century.”
Magaña and his team knew the genetic markers associated with the pathology, that is, the DNA segments that link a hereditary disease to the gene responsible, and analyzed genotype by genotype. The same haplotype, a set of variations present in one chromosome and tending to be inherited together, appeared in all individuals in the community. “100% of the ataxic sufferers showed the same origin of the mutation. What is called the founder effect in genetics: All cases come from the same ancestor,” explains the biologist.
Adelaido Torres Morales and his niece Inés Torres Ruíz in the hallway of their home. Nayeli Cruz
From the Pyrenees to the mountains of Veracruz
And how did the mutation in Tlaltetela come about? he later wondered. When researchers tried to look for the presence of these haplotypes in the native Mexican population, they found nothing. “But with matching [cruzarlas] Along with others around the world, these variations in the chromosome led us to a region in Europe,” he explains.
The comprehensive genetic analyzes led the researchers to the origin of the mutation: in the northwest of the Iberian Peninsula, in the Pyrenees, a region between the border between northern Spain and southern France, also with very high mountains. “The genetic variant in ATXN7 did not originate here in Mexico, but came from a Basque who carried the mutation, certainly a cacique who settled in the region,” says Lagaña.
Veracruz was an important migration scenario. “At the beginning of the 19th century many nationalities, goods, languages and socio-cultural practices came. But some communities remained isolated from the capital and other cities due to the lack of public transport,” explains the anthropologist.
Tlaltetela, built 960 meters above a dizzying gorge with the most impressive view of a crossroads of valleys, condemned its inhabitants to geographic and social isolation. “People didn’t leave here, they married people from their community. Therefore, inbreeding was a major factor in the development of ataxia,” explains Moctezuma. “Although there are some cases of consanguineous marriages, isolation was key to the spread of the disease: it is the factor that triggered the mutation in this region,” Magaña explains.
Edgar García, a 10-year-old patient with ataxia, eats Librada Morales with his mother. Nayeli Cruz
“If I know that my last name has brought so much bad luck, I will not get married,” Medina admits while watching her daughter in a wheelchair. Next door his little grandson with eyes that don’t look. “And there is impotence because there is nothing else that can be done but wait for the time. It’s not cured,” he adds.
A ray of light for healing
“There is no cure, but we know where it could be,” says Magaña, who has worked on the development for years a therapeutic tool to reverse the disease: a solution to eliminate or prevent the formation of mutated proteins in the brain. “There are already drugs to kill these aggregates. The problem is that no mechanism has been created that manages to cross the brain’s blood-brain barrier,” says the researcher. To avoid infection, the membrane that protects this organ is very selective and lets almost nothing through, neither viruses, nor bacteria, nor fungi. “But he doesn’t let the medication through either,” he explains.
At the same time that the pandemic was confining those affected by ataxia even more to their homes, Magaña began developing a carrier, a microscopic vehicle, in his lab to deliver the drug to the brain. “Using nanotechnology, we have developed a Trojan horse that fools this barrier, which is so difficult to cross, and delivers the drug to eliminate the mutated proteins,” he explains.
The first phase of the experiment was successful: Magaña and his team managed to create an experimental model in the laboratory that mimics what happens in the brains of patients with SCA7. “We did it in in vitro cells, the next step is to test the drugs on mice. If things go well, we can conduct the clinical trial in the same affected population of Tlaltetela whose history we know,” says the researcher, proud of the glimmer of hope his scientific advance represents. “It may be many years before the drug reaches the population, but we know we’re on the right track,” he says.
With the technological revolution brewing in a lab to stop it, type 7 ataxia has gone undetected in Mexico, where only twenty rare diseases are registered. “There is no legal framework or proper medical protocols for the care of the population with SCA7, which has led to a lack of support from the government at its various levels,” Moctezuma laments.
Marilú Peña takes the hands of her daughter Marely Hernández. Nayeli Cruz
Together with the Fundación Genes, the anthropologist is part of the team that accompanies families and tries to improve the quality of life of patients by offering genetic counseling and a diagnostic protocol in the community. “It takes a lot of awareness to give the right information. Many do not want to know whether they are sick or not. Telling them that they are carriers can be like handing them a gun,” the biologist laments.
“My brothers reject the diagnosis, they don’t want to bring children into the world either,” Melchor admits and awaits the results of the genetic test carried out a few weeks ago. “I want to know how likely it is that I will get sick and if I can have a healthy baby again. I don’t want more children in this world to suffer. But yeah, you know. What do I have to be afraid of when my girl, the love of my life, has already been taken from me?” asks the woman, who inherited the lemon growers’ surname and the spread of a deadly disease. She is also the one who knows best how the coincidence of genetics determines the fate or downfall of the residents of Tlaltetela, a marginalized town high in the mountains of Veracruz.