A team of 800 scientists in 90 Italian research centers is studying our most complex organ with unprecedented research in Europe. From digital to mini-brains, all the frontiers of the Mnesys program.
The human brain is a grayish, squishy mass of just a pound and a half, packed into a few cubic centimeters inside the skull. It is not exactly pleasant to look at, nor does it suggest its incredible capabilities: it is a true miracle of nature and the organ that more than any other defines us for what we are. It is thanks to him if we can think, get excited, feel, relate to others and to the world; thanks to its abilities the human species has been able to accomplish feats impossible for any other animal: going into space, creating masterpieces such as the Sistine Chapel or the Divine Comedytheorize quantum mechanics. Yet, the brain remains one of the most unfathomable mysteries, because it is the most complex imaginable. Try to think of an intricate mass of 150 billion cells, neurons, which establish 100 thousand billion ever-changing connections between them, constantly changing to adapt to external stimuli: the result is a network of “roads” between brain cells which, if lined up, would cover 160 thousand km, a third of the distance between the Earth and the Moon.
an ambitious project
Drawing a map of it is a titanic undertaking, as much as deciphering how thought and consciousness are formed from a tangle of chemical and electrical signals continuously passing from one neuron to another. Yet scientists have been trying for decades to get closer to the mystery of the brain, despite the enormous practical and ethical difficulties of research in neuroscience: there are not many experiments that can be carried out on humans, so for most of the studies it is necessary to resort to more or less “raw” models, from cells in vitro to the simulations possible today thanks to artificial intelligence. This is also what happens with the Mnesys program, which with around 800 researchers working in over 90 centers across the country is the largest brain research program ever carried out in Italy, as well as the largest and most cutting-edge in Europe.
Launched in 2022 for a duration of three years, this network of excellent scholars (all the best Italian brain research centers are now part of Mnesys) is trying to understand what happens in the brain when it is healthy and when it becomes ill, adding new pieces to current knowledge «for example, to discover biomarkers capable of helping us make increasingly earlier diagnoses of diseases such as Alzheimer’s, Parkinson’s or multiple sclerosis, even before they appear, so as to set up personalized therapeutic and preventive strategies, also predicting the prognosis and response to treatment”, explains Antonio Uccelli, scientific director of the Mnesys program, professor of neurology at the University of Genoa and scientific director of the IRCCS Policlinico San Martino in Genoa.
«Mnesys then aims to identify new disease mechanisms and targets for possible drugs, to improve the use of technologies for the treatment of neurological diseases and also to support the development of computational models of diseases, with simulation techniques».
This is the case of one of Mnesys’ most visionary and innovative projects, the creation of digital twins of the brain: on these avatars, created on the computer by processing personal, clinical, laboratory and diagnostic data using mathematical algorithms, it is possible to study how the nervous system works in normal and disease conditions but above all to carry out virtual experiments that overcome the limits of research on the real human brain, allowing us to better study drugs and more.
scientists’ tools
In addition to digital models, Mnesys researchers are also creating “miniature brains” to study diseases that are more difficult to replicate on single cells or in experimental animals. Starting from cells taken from patients with dementia, regressed to the stem cell stage and then “reprogrammed” to become neurons, it is possible to form in vitro the so-called organoids, mini-brains that can be used as a cellular laboratory to also test new therapies. Alongside these more cutting-edge methods, there is no shortage of projects that exploit more usual strategies such as classic studies in vitro And alivefrom investigations on single molecules to population studies: there are over 300 ongoing studies and have already led to over 600 scientific publications, with many already tangible results (see the next pages). As Uccelli adds, «for example, new biomarkers have been identified for various neurodegenerative diseases, such as neuronal pentraxin-2 (NPTX2) for Alzheimer’s. This protein is crucial for the functioning of synapses, the points of contact between neurons in which the cells “dialogue” with each other. The research used labeled glucose PET, a technique imaging which, in addition to visualizing the organ, allows you to evaluate the metabolism of the cells. It has been seen that, already during mild cognitive impairment, in some brain areas there is a correlation between the levels of NPTX2 present in the cerebrospinal fluid (which surrounds and protects the brain and spinal cord) and the alterations in glucose metabolism typical of the disease. NPTX2 is therefore a promising biomarker, both for assessing the stage of Alzheimer’s and for estimating the risk of progression.”
The Seven Spokes
The studies of the Mnesys program, divided into seven different sub-projects (called, in technical terms, spoke) coordinated by as many universities under the guidance of the University of Genoa in synergy with the San Martino Polyclinic, are not limited to investigating neurological or neurodegenerative diseases, but cover all areas of neuroscience, from the development of the brain of newborns to neuronal plasticity, from cognitive functions to movement control, from perceptions and brain-body dialogue to social and behavioral interactions.
Even in these sectors, new hypotheses, innovative theories and interesting data are emerging: for example, we are studying how to protect the neurological development of children born prematurely by adding fats with high antioxidant power, contained in olive oil, soy or fish, to the diet, but also how to improve the ability of patients with Parkinson’s and Alzheimer’s to recognize the facial expressions of others and express emotions, to help them interact and communicate better with others and thus improve the quality of life. An all-round strategy which, as Uccelli concludes, aims to «reveal the secrets of the brain but above all to develop personalized treatments for neurological and psychiatric diseases, arriving at real precision medicine also for the central nervous system».
Not only that: «Mnesys is a complex machine, but it is also a great development opportunity for the country» explains Enrico Castanini, president of Mnesys Scarl, the company that manages the entire program. «In addition to having a major impact on scientific knowledge, it can generate economic value by transferring the results to the market thanks to the involvement of the business world».
In the articles that make up this special we take you into the beating heart of this extraordinary scientific adventure, exploring one by one the seven research areas of the Mnesys program. An unprecedented journey through discoveries that are rewriting what we know about our brain.
