CNF1 as a new therapeutic approach for the treatment of Alzheimer's disease

Cytotoxic necrotising factor 1 (CNF1) treats dysfunctional astrocytes and is useful to treat conditions associated with astrogliosis and/or neuroinflammation.

Title of the patent Neurological Therapies
Thematic area Pharmaceutical
Ownership Alma Mater Studiorum - Università di Bologna e Istituto Superiore di Sanità
Inventors Gabriele Campana, Roberto Rimondini Giorgini ,Carla Fiorentini, Stefano Loizzo, , Fiorella Malchiodi Albedi, Sara Travaglione
Protection Europe, USA
Licensing status Available for licensing agreement
Keywords CNF1, Alzheimer’s disease, astrocytes, neuroinflammation, interleukin 1 beta, amyloid proteins
Filed on Jan 23, 2012

Astrocytes, the most abundant type of glial cells in the central nervous system (CNS), seem to participate in the induction of neuroinflammation, which causes many neurodegenerative diseases, including Alzheimer's disease (AD). In fact, in AD patients is observed an over-activation of brain astrocytes and glia (reactive astrogliosis) with subsequent release of pro-inflammatory cytokines, particularly interleukin-1 beta (IL- 1beta). A malfunction of astrocytes, in fact, would be the basis of the accumulation of amyloid protein in the brains of patients with AD. The Cytotoxic Necrotizing Factor type 1 (CNF1) is a protein of approximately 110 KDa produced by several strains of Escherichia coli, it can act specifically on astrocytes by reducing the production of pro-inflammatory cytokine IL-1beta in vitro and in vivo. The CNF1 is known to activate selectively and permanently Rho family GTPases, proteins involved primarily in regulation of actin cytoskeleton.

The Cytotoxic Necrotizing Factor type 1 (CNF1) is proposed as a potential therapeutic approach to counteract some of characteristic symptoms of Alzheimer's disease.  A single intracerebroventricular administration of CNF1 causes, in the hippocampus, the disappearance of astrogliosis, the reduction of IL-1beta and beta amyloid as well as the increase of ATP at the control levels.

CNF1 could represent a novel therapeutic approach for AD since it is able to significantly improve the specific disease symptoms related to hippocampal glia in a mouse model for AD, such as ApoE4. In particular, CNF1 causes the disappearance of astrogliosis in the hippocampus, a reduction of IL-1beta and beta amyloid as well as an increase of ATP at the control levels.