Gene therapy: promising discoveries against neurodegenerative diseases
15.01.2026
A study by the University of Padua demonstrates that it is possible to restore a key protein in the brain and improve symptoms of frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis type 11 (CLN11). Gene therapy with autologous haematopoietic stem cells (HSC-GT) represents a promising strategy for treating these diseases, which are caused by mutations in the GRN gene and are characterised by a deficiency of the progranulin protein (PGRN) in the brain.
In the study published in "Science Translational Medicine," researchers collected haematopoietic stem cells, genetically corrected them by inserting a functional copy of the GRN gene, and transplanted them into a mouse model of the two diseases. These cells transformed into microglia-like cells, producing progranulin in a stable manner. "In all experimental conditions, we observed a restoration of PGRN production in the central nervous system," says the corresponding author of the study, Alessandra Biffi, a professor in the Department of Women's and Children's Health at the University of Padua. "This led to a correction of lipid accumulation, a decrease in neuroinflammation (gliosis), and an improvement in behavioural functions, particularly social recognition. Of particular interest is the observation that therapeutic benefits were also achieved when the genetically modified cells settled exclusively in the brain, following intracerebroventricular administration of the treatment."
The study shows how a partial but stable reconstitution of progranulin in the brain over time is sufficient to correct the pathology, opening new perspectives for the development of effective gene therapies for the two severe and currently untreatable neurodegenerative diseases, Frontotemporal Dementia and neuronal ceroid lipofuscinosis type 11.
