Feb 09, 2026
3 min read
Professor Christian Ripoli, winner of the Mid-Career Award in 2025 from Airalzh and the Armaniz Harvard Foundation, tells us about a paradigm shift in Alzheimer's research: not only targeting the molecular causes of the disease but directly protecting and restoring synaptic function, to make the brain more resistant to cognitive decline.
The year 2026 opened with relevant news for Italian neuroscience research and Alzheimer research.Cristian Ripoli, Professor of Physiology at the Faculty of Medicine and Surgery of the Catholic University of the Sacred Heart, Rome Campus, won the Mid Career Award 2025 promoted by Airalzh (Alzheimer Society of Italy) and the Armenise Harvard Foundation.The call, intended for mid-career researchers active in the study of neurodegenerative diseases, awarded a total of 200 research funds of one thousand dollars to support lines of research with high innovation potential.
The project led by Ripoli aims to develop engineered proteins that can intervene on synaptic dysfunction, one of the central elements of Alzheimer's disease.An approach that differs from the most widespread strategies, often focused on the elimination of toxic proteins such as beta-amyloid and tau, and which instead proposes to act on the functional consequences of the pathology: the loss of neuronal plasticity and the vulnerability of the connections between neurons.
The Mid-Career Award represents not only financial support, but a real catalyst for career and ideas, aiming to advance scientific results at an important stage in a researcher's career.A model that aims to promote the transition from basic research to clinical and translational evaluation also through more customized competitive opportunities.We talked about it with Riboli.
Let's start with the recognition: What does the Airalzh Foundation and Armenise Harvard 2025 Mid-Career Award mean to you and why is this type of funding crucial for basic research in neurodegenerative diseases?
The Mid-Work Award from Airalzh and the Harvard Armenise Foundation is a recognition of great scientific value, as it will allow the continuation of a line of research that my laboratory has been carrying out for many years, which aims to develop new biotechnological strategies.The methods we have developed have two goals, on the one hand, to understand more precisely the mechanisms of nerve cell functioning and, at the same time, to confirm their potential as therapeutic tools to address the neurological and neuropsychiatric neuronal changes in many diseases.Basic research into diseases of the nervous system, such as Alzheimer's disease, is more important than ever.Unfortunately, many strategies that have been tried over the years have not yet resulted in an effective treatment.Therefore, it is important to explore new methods that can open up new possibilities.In fact, if these methods show efficacy in the clinical phase, they can form the basis for the development of future treatments.on the way.Winners will, in fact, have more competitive volunteering opportunities, such as the Sofinnova Biovelocita Call for Ideas, which aims to encourage treatment development to move from basic research to early optimization and translation.In this sense, the Mid-Work Award is a real catalyst for ideas and possible impact on neurodegenerative disease research.
The heart of the project is about the synaptic disruption of Alzheimer's disease.Can you explain in an understandable way what happens to synapses during the course of the disease and why it is a promising strategy to intervene at this level?
"In the human brain, throughout life, the number of dendritic spines (small projections on neurons, where synaptic connections are made) follows a trajectory during development, stabilizes in adulthood, and then gradually decreases with age. The ability to modify form and function in response to experience is very conducive to the onset of clinical symptoms, so Alzheimer's disease can be considered a synaptopathy, because of the death of synapses.Intervention of early synapses works.If diseases such as abnormal and toxic accumulation fail to prevent its progression, our laboratory proposes a change model: instead of trying to prevent the "ongoing" pathology, they aim to intervene on the functional consequences of the disease.
In the last quarter of 2025, the European Commission gave the green light for the marketing of donanemab. The treatment, which directly targets amyloid plaques, opens up new treatment options for hundreds of thousands of patients and caregivers in Europe.
You talk about proteins that are able to make synapses more "plastic" and resilient: how can these molecules fight cognitive decline, and how does your approach differ from treatments currently available or in development?
"Proteins represent biological agents, and even complex brain functions such as learning and memory can be traced to the proteins themselves. In our group, we started by identifying endogenous proteins important for synaptic activity, whose role has been revealed by experimental results in our laboratory and by observation and preclinical evidence developed by other research groups. Modulate mechanisms downstream of thepointing out the way he was involved At this time, we identify the protein of interest we are developing chemogenetic drugs, providing the correct molecular "switch" that allows the selection and withdrawal of its activities thanks to the support of the Mid-Career Award, we also intend to develop drugs that can be controlled by the use of drugs and the use of all drugs Treatment methods: the creation of proteins that can work quickly when specific enzymesconceived "sentinel" indicating the initial level of cellular or synaptic perturbation is an "on-demand" system that is activated in the patient's hand and only when needed for our knowledge, such as has not been tried so far.
How important is interdisciplinarity in Alzheimer's research today?
"In neuroscience, disciplines such as biology, physics, engineering and artificial intelligence converge in an increasingly integrated way. Technologies such as optogenetics or the possibility of obtaining functional human neurons from patient cells have revolutionized this field. In the context of Alzheimer's disease, this interdisciplinary approach is even more crucial. The protection of synapses, highly complex and dynamic biological systems, requires tools that go beyond classical pharmacology. In this sense, protein engineering approaches can provide innovative and targetedsolutions."
What realistic prospects for the future open the potential therapeutic effect of patients?
"Today there is a good heart in the research laboratory. Even with Alzheimer's disease, using the right experimental models, the slow progression of the pathology can be detected, and in some cases, the therapeutic part of the damaged functions can be discovered. Clinical translation is a long and difficult path, but today we can use human experimental models, such as brain cells and neurons obtained from the distance between the laboratory. For these reasons, the patient with Alzheimer's diseaseUntil we can find a cure, our mission is to get there as quickly as possible.
