A study coordinated by the CNR-ICB proposes a new therapeutic approach for Alzheimer's, focusing on strengthening the brain's natural defenses and modulating the brain's innate immunity to support neuronal function and memory. The study is published in the Journal of Neuroinflammation
Rome, February 5 2026 A study coordinated by the Institute of Biomolecular Chemistry of the National Research Council (CNR-ICB) in Pozzuoli proposes a new strategy in the fight against Alzheimer's disease (AD): focusing on strengthening the brain's natural defenses through the development of a small, "smart" molecule.
The research, conducted in collaboration with the Department of Biology of the University of Naples Federico II, the Campus Bio-Medico University of Rome and the IRCCS Fondazione Santa Lucia, is published in Journal of Neuroinflammation and describes the development of Sulfavant A, a synthetic compound patented by the CNR and already under study for its ability to enhance the body's natural defenses in the treatment of tumors, particularly melanoma, and in the fight against pathogens such as bacteria.
In preclinical models, Sulfavant A has been shown to selectively modulate the activity of microglia, the immune cells of the nervous system responsible for monitoring and removing cellular debris and protein aggregates. This is particularly relevant in Alzheimer's disease, where the extracellular accumulation of beta-amyloid peptide can aggregate into plaques, contributing to neurotoxicity and neuronal loss: a hallmark of Alzheimer's disease, currently the most common form of neurodegenerative disease.
In this context, treatment with Sulfavant A reduced, and partially prevented, plaque formation, with a protective effect on neurons and a consequent improvement in memory function. Overall, the results open up promising prospects for new therapeutic strategies in Alzheimer's disease and, more generally, other neurodegenerative diseases.
"This work suggests a genuine shift in treatment perspective, not focusing solely on the direct removal of amyloid plaques, but on supporting and strengthening the brain's endogenous defense mechanisms, with particular attention to the role of innate immunity," says Angelo Fontana, director of the CNR-ICB and coordinator of the research team. "Our research adopted an alternative approach aimed at strengthening the function of microglia, the immune cells resident in the central nervous system responsible for monitoring and removing cellular debris and beta-amyloid protein aggregates, including the initial forms that form before the onset of pathological symptoms," Fontana explains. "In particular, the study focused on modulating the clearance mechanisms already present in the brain, with the aim of selectively increasing their efficiency without solely targeting the direct destruction of the deposits."
Despite recent advances, the therapeutic options available today remain limited, making the development of innovative approaches capable of intervening early on in the disease mechanisms a priority. Research has demonstrated that Sulfavant A is able to selectively modulate microglial activity, increasing their phagocytic capacity in the early stages. "In preclinical models of Alzheimer's disease, treatment with Sulfavant A resulted in a marked reduction in beta-amyloid plaques, a decrease in signs of neuronal degeneration, and a significant improvement in performance on memory and learning tests," explains Marcello D'Amelio, head of the Molecular Neuroscience Unit at the University of Bologna.Università Campus Bio-Medico di Roma - supported by the Fondazione Roma - and responsible for the preclinical trial. "The data suggest that supporting microglial function, in addition to direct intervention on amyloid deposits, may help restore a compromised physiological balance during the disease phases."
The results indicate that enhancing the brain's innate immunity represents a promising therapeutic strategy that complements traditional approaches. "The research, supported by European and Campania Region funding," Fontana concludes, "will now move toward clinical validation, for which we hope to involve private partners, with the goal of developing safe and effective therapeutic interventions for Alzheimer's disease."
