What if viruses embedded in your DNA hold the key to stopping Alzheimer's?

When I began working in the field of virology two decades ago, searching for antiviral treatments, I never imagined that the knowledge accumulated in our field would contribute years later to the design of new therapies for Alzheimer's. However, in recent years, there has been growing interest in laboratories around the world, including our own, IrsiCaixa, in understanding the role that viruses play in the neurocognitive degeneration process linked to this type of dementia. These studies are now beginning to yield astonishing results.

When we talk about viruses, the first thing we probably imagine are those occasional, recurring infections that cause us to get colds and flu every year. What few people know is that approximately one-third of our genome comes from ancient viral infections, reflecting viruses that once infected our ancestors, integrated into their genetic material, and were passed on from generation to generation as genetic fossils.

Normally, these viral fossils are not active and do not produce any viral proteins, but at certain times they are expressed and perform key functions in our biology. For example, during pregnancy, the expression of proteins from these viral fossils on the surface of placental cells facilitates cell fusion (as occurs when a virus infects a cell), which favors the emergence of a key area for the exchange of nutrients between the embryo and the sea. It's incredible to think that we are mammals thanks to the proteins of a virus.

What is currently suspected is that, in some people, these fossilized viruses can awaken and cause chronic inflammation that can accelerate the development of neurodegenerative diseases such as Alzheimer's. This happens precisely because when one of these viral fossils is activated in a brain cell, even if it is a vestige of an ancient infection, it triggers the immune response, a cellular alarm that produces a series of molecules to contain a supposed viral infection. In this case, since these are viruses that are integrated into our genome, the alarm continues to sound constantly, inflammatory molecules accumulate in the brain, and this favors the loss of neuronal connections.

If the hypothesis about viral fossils and their relationship with the progression of Alzheimer's is confirmed, the good news is that extremely safe antivirals used to treat infections such as HIV could become new therapeutic options to slow the progression of Alzheimer's. This is precisely what studies conducted on animal models by the Center for Genomic Regulation (CRG) in Barcelona and IrsiCaixa suggest, in which animals that have followed antiviral treatment with lamivudine improve significantly after taking it.

Independent observational studies conducted on people with HIV who follow these treatments point in the same direction: their probability of developing Alzheimer's is much lower than that of those who receive antivirals that do not inactivate these viral fossils.

To determine whether antivirals such as lamivudine reduce neuroinflammation in the early stages of Alzheimer's, we have initiated a pioneering clinical study as a result of the collaboration between IrsiCaixa, the Fight Against Infections Foundation, the Pasqual Maragall Foundation, the CRG, and the Hospital's neurology department. This trial has been launched. thanks to the generosity of many anonymous donors who are helping us explore a possible therapy that could slow cognitive decline by reducing neuroinflammation with extremely safe, accessible, and inexpensive drugs.

Paradigm shift

We are undoubtedly immersed in a paradigm shift. We are increasingly understanding the genetic determinants that increase predisposition to Alzheimer's, and we even have precise diagnostic tools that allow for early detection and facilitate care planning before symptoms of the disease appear.

And although we don't currently have treatments that can cure dementia, which affects 55 million people worldwide—a figure that, according to WHO forecasts, could triple by 2050 to 152 million—we do, for the first time, have drugs that can slow the progression of this disease.

It's true that only 5% of those affected can benefit from these therapeutic options and that these treatments are not without side effects, which in some cases can be very serious. However, the impact on the course of the disease is significant and offers a glimpse of new approaches that can safely reach all those affected.