@article{CanesiGiordanoLazzarietal.2016, author = {Canesi, Margherita and Giordano, Rosaria and Lazzari, Lorenza and Isalberti, Maurizio and Isaias, Ioannis Ugo and Benti, Riccardo and Rampini, Paolo and Marotta, Giorgio and Colombo, Aurora and Cereda, Emanuele and Dipaola, Mariangela and Montemurro, Tiziana and Vigano, Mariele and Budelli, Silvia and Montelatici, Elisa and Lavazza, Cristiana and Cortelezzi, Agostino and Pezzoli, Gianni}, title = {Finding a new therapeutic approach for no-option Parkinsonisms: mesenchymal stromal cells for progressive supranuclear palsy}, series = {Journal of Translational Medicine}, volume = {14}, journal = {Journal of Translational Medicine}, number = {127}, doi = {10.1186/s12967-016-0880-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165725}, pages = {1-11}, year = {2016}, abstract = {Background: The trophic, anti-apoptotic and regenerative effects of bone marrow mesenchymal stromal cells (MSC) may reduce neuronal cell loss in neurodegenerative disorders. Methods: We used MSC as a novel candidate therapeutic tool in a pilot phase-I study for patients affected by progressive supranuclear palsy (PSP), a rare, severe and no-option form of Parkinsonism. Five patients received the cells by infusion into the cerebral arteries. Effects were assessed using the best available motor function rating scales (UPDRS, Hoehn and Yahr, PSP rating scale), as well as neuropsychological assessments, gait analysis and brain imaging before and after cell administration. Results: One year after cell infusion, all treated patients were alive, except one, who died 9 months after the infusion for reasons not related to cell administration or to disease progression (accidental fall). In all treated patients motor function rating scales remained stable for at least six-months during the one-year follow-up. Conclusions: We have demonstrated for the first time that MSC administration is feasible in subjects with PSP. In these patients, in whom deterioration of motor function is invariably rapid, we recorded clinical stabilization for at least 6 months. These encouraging results pave the way to the next randomized, placebo-controlled phase-II study that will definitively provide information on the efficacy of this innovative approach.}, language = {en} } @article{GiordanoCanesiIsalbertietal.2014, author = {Giordano, Rosaria and Canesi, Margherita and Isalberti, Maurizio and Isaias, Ioannis Ugo and Montemurro, Tiziana and Vigan{\`o}, Mariele and Montelatici, Elisa and Boldrin, Valentina and Benti, Riccardo and Cortelezzi, Agostino and Fracchiolla, Nicola and Lazzari, Lorenza and Pezzoli, Gianni}, title = {Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study}, series = {Journal of Translational Medicine}, volume = {12}, journal = {Journal of Translational Medicine}, number = {14}, doi = {10.1186/1479-5876-12-14}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117594}, year = {2014}, abstract = {Background: Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of tauopathies and involves both cortical and subcortical structures. No effective therapy is to date available. Methods/design: Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors. Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection. Discussion: To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this " first-in-man" approach and to preliminarily explore its efficacy by excluding the placebo effect. Trial registration: NCT01824121}, language = {en} } @article{IsaiasMarzeganPezzolietal.2012, author = {Isaias, Ioannis U. and Marzegan, Alberto and Pezzoli, Gianni and Marotta, Giorgio and Canesi, Margherita and Biella, Gabriele E. M. and Volkmann, Jens and Cavallari, Paolo}, title = {A role for locus coeruleus in Parkinson tremor}, series = {Frontiers in Human Neuroscience}, volume = {5}, journal = {Frontiers in Human Neuroscience}, number = {179}, doi = {10.3389/fnhum.2011.00179}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133955}, year = {2012}, abstract = {We analyzed rest tremor, one of the etiologically most elusive hallmarks of Parkinson disease(PD), in 12 consecutive PD patients during a specific task activating the locus coeruleus (LC) to investigate a putative role of noradrenaline (NA) in tremor generation and suppression. Clinical diagnosis was confirmed in all subjects by reduced dopamine reuptake transporter (DAT) binding values investigated by single photon computed tomography imaging (SPECT) with [\(^{123}\)I] N-\(\omega\)-fluoropropyl-2 \(\beta\)-carbomethoxy-3 \(\beta\)-(4-iodophenyl) tropane (FP-CIT). The intensity of tremor (i.e., the power of Electromyography [EMG] signals), but not its frequency, significantly increased during the task. In six subjects, tremor appeared selectively during the task. In a second part of the study, we retrospectively reviewed SPECT with FP-CIT data and confirmed the lack of correlation between dopaminergic loss and tremor by comparing DAT binding values of 82 PD subjects with bilateral tremor (n = 27), unilateral tremor (n = 22), and no tremor (n = 33). This study suggests a role of the LC in Parkinson tremor.}, language = {en} }