A “fascinating” project that captures the genetic sensitivity to music of people with Alzheimer’s

Just one year ago, on September 30 and October 1, 2022, an unusual mosaic of people gathered in the stalls of the Auditorio de Galicia, in Santiago de Compostela, to attend surprise concerts by the Real Filharmonía. Under the baton of Baldur Brönnimann, its director, the musicians performed seven scores by Charles Ives, Otto Nicolai, Dvořák, Piazzolla, Brahms, Rossini and Arturo Márquez for one hour. Before and immediately after the recital, an army of 200 public health volunteers took saliva and blood samples from attendees, from the elderly to children, from the healthy to the sick: especially Alzheimer’s patients, people with Down syndrome, ADHD, autism, cancer or brain damage. The music had been selected for the enormous palette of feelings that together they could transmit.

The aim was to verify whether the newest techniques in neuroscience were capable of photographing the molecular fingerprint of these sensations and detecting changes in the expression of genes, as well as knowing whether these reactions were different in people depending on whether pathologies existed or not. . After a few weeks of analysis, focused on patients with Alzheimer’s, there were already “surprising” results. Now, the word that neuroscientist Antonio Salas, one of the promoters of the Sensoxenoma Project, likes to use is “fascinating.” The genes played by music are not only expressed in a much more exaggerated way in people with neurodegenerative ailments, but they do so in the “opposite direction” to their usual evolution, as if the melody caused a “compensatory effect” of the mechanisms of the disease.

After several articles published, the last one these days in the BioRxiv magazine, the call from the Filharmonía de Galicia (RFG) and the IDIS (Health Research Institute), based at the Complexo Hospitalario Universitario de Santiago (CHUS), is going to repeat on September 29 and 30, and several associations supporting sick people and a couple of secondary schools will collaborate. This time, according to the orchestra’s technical director, Sabela García Fonte, the scores to be performed will be grouped – as in 2022 within a repertoire kept secret – into two differentiated blocks, according to the emotions they are capable of. to transmit. More than 2,000 people attended last year’s concerts, and the results prove that the melodies not only impact the genes related to emotions, but also press keys in the DNA that are associated with “cognitive and memory” functions, such as and as explained last Tuesday by the souls of the project: Antonio Salas, principal investigator of Sensogenoma and professor of Medicine in Santiago, and Federico Martinón, head of the Pediatrics service at the University Hospital Complex of the Galician capital.

The first evidence from the project being developed at IDIS with support from the University of Santiago (USC) opens doors to understanding the beneficial effect of music on people with cognitive impairment and moving towards the future development of specific molecular targets. However, the researchers admit that “it is still too early” to know “the persistence of the effect” of music, the “long-term impact” or whether it “stimulates or inhibits.” The study analyzed the universe of molecules that are expressed from a person’s DNA in response to a musical stimulus, what is known as the transcriptome. DNA remains more or less stable throughout life, but the transcriptome is dynamic and reflects a person’s response to changes in the environment or resulting from age, sensory stimuli, nutrition or The diseases. One of the most striking findings of the team is that “people with dementia have a greater sensitivity to music, if by this we mean the number of genes that modify their expression with musical stimulation and in comparison with healthy people”, explains Salas. In the second phase of the project, the Compostela laboratory is analyzing samples from donors diagnosed with autism spectrum disorders who attended last year’s recitals.

The results refer to samples of people with “age-related cognitive disorders.” Among the patients analyzed “there are those with a milder impairment (MCI or mild cognitive impairment) and Alzheimer’s,” Antonio Salas details to EL PAÍS, “therefore, not all of them have dementia, if technically we understand that MCI is not, if no, let’s say, a previous step.” “When I say that they have greater sensitivity to music, I am referring to the fact that there are many more genes that are stimulated in these patients than in the healthy controls (with which we compare them),” the professor explains, “on the order of 2 .3 times more… specifically 2,605 genes compared to 1,148″ in donors without these diagnosed pathologies.

The research is advancing hand in hand with the multidisciplinary groups GenPoB (Population Genetics Group in Biomedicine) and GenViP (Research Group on Genetics, Vaccines and Infectious Diseases) of the USC and IDIS, for the moment without the financial sponsorships that they would like to obtain. to move faster. Despite this, according to Salas Ellacuriaga, the discoveries of this first year far exceed initial expectations: “The truth is that I didn’t think so many things would come out,” says the scientist, “not even in the best of our dreams did we imagine we would obtain results.” “so surprising, both for the technical challenge and for the value and significance of the findings.”

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“We are excited about the work done,” confesses Martinón Torres, “we have thousands of hypotheses and thousands of samples, we have plenty of ideas but we lack resources.” “So far we have had very good words from companies, basically,” acknowledges the head of Pediatrics, who however appreciates the support received from a distribution firm in the food sector and a social foundation in A Coruña. “It is much more difficult to get funds for this than for our other projects,” acknowledges the doctor, “because it is not easy to bet on something so novel, which can be very successful or go nowhere.”

But the graphs published so far in which it is clearly seen how groups of genes light up “like LEDs” with music seem to predict the former. “Music modifies the expression of more than twice as many genes as in people without diagnosed pathology, and many of these are related to neurodegenerative processes,” explains Salas. These differentially expressed genes tend to be over-expressed (they are expressed more than usual), while those of people without impairment tend to be expressed below normal, the professor specifies. “And the most surprising thing is that the musical stimulus causes the vast majority of genes to express themselves in the opposite direction to what they normally do in patients with cognitive impairment,” the researcher continues to describe, it is therefore “intuitive to think that this effect “of music implies a compensation in the genes altered in Alzheimer’s, as if it were a therapeutic effect.”

Real Filharmonía in the Auditorio de Galicia, in an image provided by the orchestra itself.

The team detected hundreds of genes with altered expression, such as the one identified as GATA2 (linked by recent studies with neurodegenerative diseases) or GIGYF1 (this other one related, in addition to these ailments, to autism spectrum disorders). “There is still a long way to go until we know the specific role that each of them plays in the response to musical stimuli,” warns Salas. But what we have seen so far helps to understand the biological pathways where all these genes are involved, “the orchestrated work they carry out in response to musical stimuli.” The genetic pathways that are most modified by music in sick people are closely related to cognitive impairment, such as cellular autophagy (the process of eliminating damaged cells and cleaning, essential for the proliferation of new and healthy cells) or accumulation of beta-amyloid bodies (a process that precedes the development of Alzheimer’s).

Martinón indicates that “it is in neurodegenerative diseases, cerebral palsy or autism spectrum disorder, where we have more and more evidence that points to the benefits of music in the disease.” At the Sensoxenoma23 concerts, samples will be taken from deaf, blind and autistic donors.

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