Francisco Lopera: “Nature teaches us that we can delay the symptoms of Alzheimer’s by 30 years” | Health & Wellness | The USA Print

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Francisco Lopera, director of the Neuroscience Group at the University of Antioquia, at his home in Itagüí, south of Medellín.
Francisco Lopera, director of the Neuroscience Group at the University of Antioquia, at his home in Itagüí, south of Medellín.santiago table

Colombian doctor Francisco Lopera Restrepo (Aragón, Antioquia, 71 years old) has dedicated more than half his life to investigating the causes and possible cures of Alzheimer’s, a neurodegenerative disease that today more than 40 million people suffer from in the world. Lopera, current director of the Neuroscience Group at the University of Antioquia, in Medellín, has worked for four decades with more than 6,000 members of 25 families from a Colombian town who suffer from genetic or hereditary Alzheimer’s. “Yarumal is the place in the world with the largest population of this type of Alzheimer’s. The secret against the disease may be there”, explains Lopera.

The researcher, who in 2020 became the only Latin American to win the prestigious award Bengt Winblad Lifetime Achievement Due to his fight against Alzheimer’s, he is optimistic about the possibility of preventing it: “Nature teaches us that we can delay the appearance of symptoms by 30 years.” Lopera says this because of the case of Aliria Rosa Piedrahita, the only woman in the world who had the Alzheimer’s gene in her biology and, at the same time, the one that cured her. “His case of her was a natural experiment. We realized that her brain was protected by a mutation that prevented the disease from developing, ”says Lopera. Aliria Rosa Piedrahita, like the other members of her family, was supposed to start developing symptoms at the age of 40 and die at the age of 60, but when the scientists met her she was 70 and she remembered everything very well, she was alive and healthy . She had lived without signs of the condition 30 years longer than expected. She only began to experience some symptoms at age 72 and she died of cancer six years later without developing serious dementia.

In practical terms, says the doctor, this woman showed science a way to prevent Alzheimer’s. “Now you just have to follow it,” she explains. And he reveals that, in three months, he and his research group are going to publish a new scientific study that shows how Aliria’s brain worked and another with the results of a clinical trial that has just ended to find out the effectiveness of a drug against the ailment

Francisco Lopera has dedicated the last 40 years of his life to researching Alzheimer's
Francisco Lopera has dedicated the last 40 years of his life to researching Alzheimer’ssantiago table

Ask. What was the latest clinical trial about?

Response. It was a study that began in 2013 and ended in March 2022. We did it in partnership with the United States Institute of Health, the Arizona Banner Institute and the Genentech company. It was aimed at healthy people and people who had the Yarumal Alzheimer’s mutation but had not yet developed any symptoms. The idea was to offer them an experimental treatment with a monoclonal antibody that cleans the brain of amyloid, one of the proteins that causes Alzheimer’s. The research was scheduled for five years and 300 volunteers, but we were only able to work with 252. To solve this statistical problem, we extended the study to eight years.

P. What did they conclude?

R. We continue to analyze the data to conclude whether this drug is capable of delaying the symptoms of the disease in this population. We will present the findings at the International Alzheimer’s Association meeting in San Diego, California, on August 2 this year. I can tell you one thing: we are optimistic. We know that these drugs have not worked in the past, but our hypothesis is that the failure occurs because they have been applied too late, when the cognitive damage has already been done. So we’re hopeful that by using this drug preclinically, before the person has symptoms, we can be more successful.

P. Do you think that if amyloid is removed from the brain, the symptoms can be delayed?

R. That’s how it is. Eliminating amyloid, which is an extracellular protein debris that is deposited in the brain of people with genetic Alzheimer’s at age 28, could inhibit the production of tauopathy, an alteration of tau proteins, which in this population begins 10 years later, at 38, and is responsible for the symptoms of Alzheimer’s. That is, if we eliminate the amyloid in the early stages, we could start to reduce the disease. That is the goal.

P. People from Yarumal, with genetic Alzheimer’s, are ideal for these trials because doctors know who will develop the disease. Does this make Colombia a privileged place for research?

R. Yes. These families are necessary for all disease prevention studies. Colombia has the largest population of genetic Alzheimer’s in the world and Yarumal the largest in Colombia. Remember that genetic Alzheimer’s is only 1% of all Alzheimer’s cases, the other variant is called sporadic. Our studies aspire to serve to prevent both types. We believe that what is discovered in the genetics is applicable to the population that is going to suffer from sporadic disease because the symptoms are the same, what varies is the origin. In the genetic we know that it develops due to a mutation of a gene, in the sporadic the cause is still not clear.

P. Studying the mutations of these Yarumal families, they discovered the case of Aliria, the only woman in the world with the Alzheimer’s gene and, at the same time, the one with the cure. How was that meeting?

R. Aliria was an exceptional woman on the planet. She was the only carrier of two apparently contradictory genetic mutations: one that condemned her to Alzheimer’s disease at the age of 44 and another that protected her until she was 70. When we met her we thought there was a mistake, we had to make several blood tests to confirm. With it, nature taught us that we can delay the appearance of its symptoms by 30 years. She collaborated a lot with the investigation, traveled three times to Boston [Estados Unidos] to get check-ups and, when he passed away, his family donated his brain for research.

P. What did they discover in his brain?

P. We found that she carried the Presenilin 1 gene, the e280a mutation, which made her sick, and the APOE 3 Christchurch mutation, that protected her. As I tell my students: nature, through Aliria, is teaching us the prevention or cure of Alzheimer’s. I think that if we can mimic what the Christchurch mutation does in people who have the disease, we could delay the onset of symptoms by 30 years.

P. Is it possible to reproduce that gene in the body of those who do not have it?

R. Yes, you could do, for example, gene therapy: take a virus, extract everything it has inside and put the protective genetic information on it and produce an infection in the body so that the person receives the protection they need. That, technically, is still complicated, but theoretically it is possible. The other option is to develop drugs that mimic the mechanism of action of the protective gene in the brain. There are many research groups working on it. From Colombia we send a message to the scientists of the world: we can change the dream of delaying the onset of Alzheimer’s symptoms for five years by delaying them 30. In practice, that would be the cure for the disease. There is hope.

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