Neuroscience
Gene therapy of neurodegenerative diseases
The goal of Gene therapy of neurodegenerative diseases Unit is to develop innovative gene and cell therapies for neurological diseases.
Research activity
- Development of gene therapy vectors for neurological diseases, based on herpes simplex;
- Involvement of neurotrophic factors in the development of lesional epilepsies: identification of new therapeutic targets and development of new delivery strategies (gene therapy);
- Neuropeptide systems (dynorphin, OFQ/N, somatostatin, NPY, bradykinin) as therapeutic targets for temporal lobe epilepsy;
- MicroRNA as biomarkers and therapeutic targets for temporal lobe epilepsy.
Ingusci S, Cattaneo S, Verlengia G, Zucchini S, Simonato M. A Matter of Genes: The Hurdles of Gene Therapy for Epilepsy. Epilepsy Curr. 19, 38-43, 2019.
Paolone G, Falcicchia C, Lovisari F, Kokaia M, Bell WJ, Fradet T, Barbieri M, Wahlberg LU, Emerich DF, Simonato M. Long-Term, Targeted Delivery of GDNF from Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy. J Neurosci. 39, 2144-56, 2019.
Nanobashvili A, Melin E, Emerich D, Tornøe J, Simonato M, Wahlberg L, Kokaia M. Unilateral ex vivo gene therapy by GDNF in epileptic rats. Gene Ther. 26, 65-74, 2019.
Han F, Miyagawa Y, Verlengia G, Ingusci S, Soukupova M, Simonato M, Glorioso JC, Cohen JB. Cellular Antisilencing Elements Support Transgene Expression from Herpes Simplex Virus Vectors in the Absence of Immediate Early Gene Expression. J Virol. 92, e00536-18, 2018.
Falcicchia C, Paolone G, Emerich DF, Lovisari F, Bell WJ, Fradet T, Wahlberg LU, Simonato M. Seizure- Suppressant and Neuroprotective Effects of Encapsulated BDNF-Producing Cells in a Rat Model of Temporal Lobe Epilepsy. Mol Ther Methods Clin Dev. 2018 Mar 9;9:211-224.
Srivastava PK, Roncon P, Lukasiuk K, Gorter JA, Aronica E, Pitkänen A, Petretto E, Johnson MR, Simonato M. Meta- Analysis of MicroRNAs Dysregulated in the Hippocampal Dentate Gyrus of Animal Models of Epilepsy. eNeuro 4(6), 2017.
Verlengia G, Miyagawa Y, Ingusci S, Cohen JB, Simonato M, Glorioso JC. Engineered HSV vector achieves safe long-term transgene expression in the central nervous system. Sci Rep. 7, 1507, 2017.
Pitkänen A, Löscher W, Vezzani A, Becker AJ, Simonato M, Lukasiuk K, Gröhn O, Bankstahl JP, Friedman A, Aronica E, Gorter JA, Ravizza T, Sisodiya S, Kokaia M, Beck H. Biomarkers in Epilepsy. Lancet Neurol. 15, 843-56, 2016.
Johnson MR, Behmoaras J, Bottolo L, Krishnan ML, Pernhorst K, Meza Santoscoy PL, Rossetti T, Speed D, Srivastava PK, Chadeau-Hyam M, Hajji N, Dabrowska A, Rotival M, Razzaghi B, Kovac S, Wanisch K, Grillo F, Slaviero A, Langley SR, Shkura K, Roncon P, De T, Mattheisen M, Niehusmann P, O'Brien TJ, Petrovski S, von Lehe M, Hoffmann P, Eriksson J, Coffey A, Cichon S, Walker M, Simonato M, Danis B, Mazzuferi M, Foerch P, Schoch S, De Paola V, Kaminski RM, Cunliffe VT, Becker AJ, Petretto E. Systems-genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus. Nature Comm 6:6031, 2015.
Simonato M, Brooks-Kayal AR, Engel J Jr, Galanopoulou AS, Jensen FE, Moshé SL, O'Brien TJ, Pitkanen A, Wilcox KS, French JA. The challenge and promise of anti-epileptic therapy development in animal models. Lancet Neurol 13, 949-60, 2014.
Simonato M, Bennett J, Boulis NM, Castro MG, Fink DJ, Goins WF, Gray SJ, Lowenstein PR, Vandenberghe LH, Wilson TJ, Wolfe JH, Glorioso JC. Progress in gene therapy for neurological disorders. Nat Rev Neurol 9, 277-291, 2013.
Mazzuferi M, Palma E, Martinello K, Maiolino F, Roseti C, Fucile S, Fabene PF, Schio F, Pellitteri M, Sperk G, Miledi R, Eusebi F, Simonato M. Enhancement of GABAA-current run-down in the hippocampus occurs at the time of the first spontaneous seizure in a model of temporal lobe epilepsy. Proc Natl Acad Sci USA 107, 3180-3185, 2010.
Paradiso B., Marconi P., Zucchini S., Berto E., Binaschi A., Bozac A., Buzzi A., Mazzuferi M, Magri E., Navarro Mora G., Rodi D., Su T., Volpi I., Zanetti L., Marzola A., Manservigi R., Fabene P.F., Simonato M. Localized delivery of FGF-2 and BDNF reduces spontaneous seizures in an epilepsy model. Proc Natl Acad Sci USA, 106, 7191-7196, 2009.
Zucchini S., Buzzi A., Barbieri M., Rodi D., Paradiso B., Binaschi A., Coffin J.D., Marzola A., Cifelli P., Belluzzi O., Simonato M. FGF-2 overexpression increases excitability and seizure susceptibility but decreases seizure-induced cell loss. J. Neurosci. 28, 13112-13124, 2008.
Palma E., Roseti C., Maiolino F., Fucile S., Martinello K., Mazzuferi M., Aronica E., Manfredi M., Esposito V., Cantore G., Miledi R., Simonato M., Eusebi F. GABAA-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABAA"phasic" receptors. Proc. Natl. 2007
