The research of Antonino Cattaneo has been inspired by the classical and seminal experiments of Rita Levi Montalcini on immunosympathectomy, whereby she exploited the use of anti NGF antibodies to formally demonstrate the role of Nerve Growth Factor (NGF) in vivo.
In fact, the scientific career of Antonino Cattaneo has followed a parallel track, combining molecular neurobiology together with the development of technologies exploiting recombinant antibodies for protein knock-out (neuroantibodies and intrabodies), with a particular focus on CNS applications. In this field, Cattaneo has pioneered and developed the neuroantibody strategy, whereby the expression of recombinant antibodies in the CNS is used to interfere with neuronal functions, creating experimental models for mechanistic studies. In further developments, Cattaneo has developed the targeting and use of intracellular antibodies (intrabodies) to achieve protein knock-out in different subcellular compartments. This has allowed to develop transgenic models, based on the expression of recombinant antibodies to NGF in the brain of adult transgenic mice, and to demonstrate that interfering with the function of NGF in the adult Central Nervous System leads to a progressive neurodegenerative phenotype that recapitulates in a comprehensive way most of the major hallmarks of Alzheimer’s Disease (AD). This work allowed to extend our understanding of the role of NGF in the CNS and to link the signalling of NGF and of its precursor form proNGF to phenotypic endpoints relevant for Alzheimer’s disease (AD). This led to formulate the hypothesis of “too little NGF-too much proNGF” as a new framework for the study of Alzheimer’s disease pathological mechanisms. Since, in a therapeutical perspective, NGF needs to be locally delivered to the CNS, in order to avoid conflicting undesired effects by NGF on peripheral targets, Cattaneo has exploited and developed an intranasal delivery route for the access of NGF to the brain, obtaining conclusive proof of principle evidence for the ability of olfactory delivered NGF to rescue neurodegeneration in animal models. He is currently developing, as a potential therapeutic for Alzheimer´s Disease, "painless NGF", a variant of NGF optimized to remove the pain sensitizing activity of NGF, that has limited its therapeutical applications sofar. Two humanized antibodies developed by Cattaneo are currently undergoing clinical development by industrial partners.
Please see also: http://www.fondazionebri.eu/index.php/en/prof-antonino-cattaneo
Tiveron C. et al. (2013) proNGF/NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice. Cell Death and Differ., in press.
Capsoni S., Marinelli S., Ceci M., Vignone D., Amato G., Malerba F., Paoletti F., Meli G., Viegi A., Pavone F., Cattaneo A. (2012) Intranasal "painless" Human Nerve Growth Factors Slows Amyloid Neurodegeneration and Prevents Memory Deficits in App X PS1 Mice. PLoS One, 7: e37555.
Capsoni S., Covaceuszach S., Marinelli S., Ceci M., Bernardo A., Minghetti L., Ugolini G., Pavone F., Cattaneo A. (2011) Taking pain out of NGF: a "painless" NGF mutant, linked to hereditary sensory autonomic neuropathy type V, with full neurotrophic activity. PLoS One, 6(2): e17321
Capsoni S., Tiveron C., Amato G., Vignone D., Cattaneo A. (2010) Dissecting the involvement of Tropomyosin kinase A and p75 neurotrophin receptor signaling in NGF deficit-induced neurodegeneration. Proc. Natl. Acad. Sci. U S A, 107 (27): 12299-12304.
Meli G., Visintin M., Cannistraci I., Cattaneo A. (2009) Direct in vivo intracellular selection of conformation-sensitive antibody domains targeting Alzheimer´s amyloid-beta oligomers. J. Mol. Biol., 387 (3): 584-606.
2009 Member of the Accademia delle Scienze dei XL
2008 Visiting Fellow at the Trinity College (Cambridge University, UK)
2008 The “G.Tartufari” International Prize for Biology, Accademia Nazionale dei Lincei
2000 Member of the Scientific Advisory Committee of the Armenise Harvard Foundation, Career Awards (until 2003)
1994 The Domenico Marotta Prize, Italian Academy of Sciences XL
1994 Human Science Frontier Organization (HFSPO) Member of the HFSPO Grants Review Committee (until 1999)
Chairman of the Grant Review Committee and member of the HFSPO Council of Scientists
1991 Member of the European Molecular Biology Organization (EMBO)
1985 Fellow of the Clare Hall College (Cambridge University, UK) (until 1987)