GREEN TEA, KEY IN THE RESEARCH ON DOWN'S SYNDROME

The team led by Mara Dierssen has discovered that there is a substance in this plant that promotes cognitive advancement

Mara Dierssen Sotos studied medicine but always wanted to be a scientific researcher. “What really interested me to understand was how the human brain worked and how, specifically, we are capable of storing information. How from this network of cells and molecules arises what we call mental activity: thought, ideas, emotions ”, he says. That is why he decided to do his doctorate in neurobiology and a thesis in neuropharmacology. 

He was working in the laboratory of Professor Jesús Flórez in Cantabria when his interest in Down syndrome aroused. "He has a daughter with this syndrome and I asked him if we could investigate along these lines," he recalls. They could only start later after the creation of the first trisomic mouse model.

"When we had the opportunity to have an animal model that would finally allow us to study the neurobiology of these cognitive alterations, that was when we decided to start a line of research that has continued until today," says Dierssen. Specifically, they study which genes are on chromosome 21, since Down syndrome is a trisomy of that gene, which means that whoever suffers from this genetic disorder has three different copies of that chromosome and, therefore, they have everything a group of genes that are in excess.   What Dierssen and his team are trying to understand is how this excess dose leads to alterations in learning memory, which genes could be the best candidates to explain these alterations and what to do to normalize it. For a long time they were trying to find which of all those that make up chromosome 21 could be more related to memory and learning processes until they found their target.   "We were lucky that it was also a good pharmacological candidate, since it was an enzyme, an echinase, a kind of molecular switch that has the power to influence many other things," he explains. The way to find out if that gene was important was to overdose it with all the other genes at normal levels and see if, on its own, it was capable of altering the gene it must correct. And it happened.  Dierssen and his team found the gene on chromosome 21 related to memory and learning.

"We overdosed this kinase, which is called dirc 1, and what we saw is that it was sufficient to produce the learning and memory alterations in the mouse, but also the neuronal alterations that we think underlie these cognitive changes", aim. The next step was to carry out this experiment in the trisomic mouse, where I found that by normalizing dirc 1 it was possible to correct learning deficits and also neuronal alterations.   For the next phase they had to find a substance that had inhibitory properties on dirc 1 and green tea was the key. "It is a catechin, epigallocatechin gallate, which is in green tea and which normalizes the excess dose of dirc 1". A peculiarity of this substance is that it favors the plasticity that one achieves when learning, therefore “it is not a magic pill, but rather it is something that helps what you do with stimulation and with early intervention have a more effective effect. It is much more physiological but it requires the person to make an effort as well ”, points out the researcher. The brain only learns through effort. "Things that do not cost, do not leave a mark," he sums up.   They have started a study with children between the ages of six and 12 in which three  hospitals and two medical institutes   Since 2012 they have carried out two trials with this substance. The first, in adulthood. After seeing that the drug was safe, they tested it among people with Down syndrome to see if it produced an improvement in their condition and the result was positive as they appreciated some cognitive advance. 

Dierssen points out that the results are more complicated to see at these ages because the person carries a whole series of defects in their neurodevelopment from the moment they are born. That is why they have begun a multicenter clinical safety study with a population between six and 12 years old in which the Hospital Niño Jesús (Madrid), the Instituto Hispalense de Pediatría (Seville), the Hospital Universitario Marqués de Valdecilla (Santander), the Hospital del Mar (Barcelona) and the Jérôme Lejeune Institute (Paris).

"The idea is that at those ages there is much more plastic capacity in the brain and we think - and we hope - that this catechin will be much more effective in them", he confides. They plan to have this first phase ready next year and start with the second as soon as possible. At that time they will know if the substance works as expected in children. "We would have gone much faster if we had had resources, but the lack of financial funds has delayed us a lot," he says.