A study coordinated by theInstitute of Biomolecular Chemistry of the National Research Council (CNR-ICB) in Pozzuoli proposes a new strategy in the fight against Alzheimer's disease (AD): focus on strengthening the brain's natural defenses through the development of a small "smart" molecule. The research was conducted in collaboration with the Department of Biology, University of Naples Federico II, L 'Università Campus Bio-Medico di Roma el 'IRCCS Santa Lucia Foundation, and is published in the scientific journal Journal of Neuroinflammation.
The study describes the development of Sulfavant A, a synthetic compound patented by the CNR and already the subject of previous research for its ability to enhance the body's natural defenses, particularly in the treatment of tumors – such as melanoma – and in the fight against pathogens such as bacteria.
In preclinical models, Sulfavant A has been shown to selectively modulate microglial activity, the immune cells of the central nervous system responsible for the surveillance and removal of cellular debris and protein aggregates.
This mechanism plays a central role in Alzheimer's disease, in which the extracellular accumulation of beta-amyloid peptide It can aggregate into plaques, contributing to neurotoxicity and neuronal loss. This is one of the hallmarks of Alzheimer's disease, currently the most common form of neurodegenerative disease.
In this context, treatment with Sulfavant A reduced, and partly prevented, plaque formation, showing a protective effect on neurons and a improvement of memory functions.
"The work suggests a real shift in perspective in the treatment of the disease, that is, not focusing exclusively 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.", he claims Angelo Fontana, Director of the Cnr-Icb and coordinator of the team of researchers.
"Our research took an alternative approach aimed at strengthening the function of microglia, the immune cells resident in the central nervous system responsible for the surveillance and removal of cellular debris and beta-amyloid protein aggregates, including the early forms that form before the onset of pathological symptoms.", explains Fontana. "In particular, the study focused on modulating the clearance mechanisms already present in the brain, with the aim of selectively increasing their efficiency without exclusively intervening on the direct destruction of the deposits."
Despite recent advances, the therapeutic options currently available for Alzheimer's remain limited, making the development of innovative approaches capable of intervening early on in the mechanisms of the disease. "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 Marcellus D'Amelio, Head of the Molecular Neuroscience Research Unit UCBM – supported by the Rome Foundation – and responsible for preclinical testing. "The data suggest that supporting microglial function, in addition to direct intervention on amyloid deposits, may contribute to restoring a compromised physiological balance in the disease phases.".
The results indicate that the enhancement of brain innate immunity It represents a promising therapeutic strategy that complements traditional approaches. The research, supported by European and Campania Region funding,, concludes Fontana, "It will now proceed towards clinical validation, for which we hope to involve private partners, with the aim of developing safe and effective therapeutic interventions for Alzheimer's disease."
