Dr. Stefano Previtali Lab

Lab Members:

Stefano Previtali, Head

Isabella Lorenzetti, Technician

Rossana Tonlorenzi, Technician,

Emanuela Porrello, Postdoc

Cristina Rivellini, Postdoc

Rosa Bonaccorso, Postdoc

Michela Molina, Student

Our lab is interested in the way cells interact with each others and with the extracellular matrix, and how this affects the cytoskeleton in order to move, survive and differentiate into complex tissues such as peripheral nerves and muscles. We apply these biological questions to the development of neuromuscular tissues, with the final goal to translate basic findings on normal development into treatment for those inherited neuromuscular diseases where these interactions fail. In particular, we are interested in Charcot-Marie-Tooth neuropathies and congenital muscular dystrophies.

To reach these goals, we exploit murine transgenic models and in vitro system.

We are also involved in the diagnosis and therapy of neuropathies and muscle disorders.

We are performing deep phenotyping of neuromuscolar disorders, primarily inherited peripheral neuropathies and muscular dystrophies.

We are also performing clinical trials for Duchenne Muscular Dystrophy.

Finally, we are performing natural history studies for CMT and DMD disorders.

Diagnosi, follow up e terapia di pazienti affetti da malattie neuromuscolari

Studi clinici dedicati alle malattie neuromuscolari

Studi di storia naturale per CMT e distrofie muscolari

Ambulatorio dedicato per Miopatie e Neuropatie genetiche

Per appuntamenti:

CUP Telefono 0226432643

Per consulti in Telemedicina: https://hsr.welcomedicine.it/

We are exploiting human pathology together with cells and mouse models to unravel molecular mechanisms sustaining muscle degeneration and defective regeneration in Duchenne and LAMA2 Muscular Dystrophy.

In the last years we demonstrated that stem cell mesoangioblasts, engineered to release the linker molecule mini-agrin, can ameliorate motor performances in mouse models of LAMA2 Muscular Dystrophy. Mini-agrin forms a link between orphan laminin2 receptors on the skeletal muscle fibers and the other laminin isoforms overexpressed in the absence of laminin2. More recently we are testing new small molecules to ameliorate Lama2 disease in animal models.

We also performed first-in-human cell therapy with mesoangioblasts and concluded phase I clinical study.

 Our Lab is interested to investigate the molecular machinery involved in the regulation of radial sorting of axons in peripheral nerve development and in disease. Abnormal radial sorting in fact results in dysmyelinating neuropathies, as those associated to LAMA2-related disease.

We are also involved in studying pathogenesis of CMT neuropathies with in vitro (IPS and Schwann cell-neuron cocultures) and in vivo models, and to set up preclinical studies to ameliorate these inherited diseases.

• Romano et al, Alteration of the late endocytic pathway in Charcot-Marie-Tooth type 2B disease., Cell Mol Life Sci. 2020
• Longo et al, Impaired turnover of hyperfused mitochondria in severe axonal neuropathy due to a novel DRP1 mutation., Hum Mol Genet 2020
• Previtali SC et al, Expanding the spectrum of genes responsible for hereditary motor neuropathies. J Neurol Neurosurg Psychiatry. 2019
• Pareyson D et al, A multicentre retrospective study of Charcot-Marie-Tooth disease type 4B (CMT4B) due to mutations in Myotubularin-related proteins (MTMRs). Annals of Neurology 2019
• Previtali SC et al, Expanding The Central Nervous System Disease Spectrum Associated WITH Flnc Mutation. Muscle Nerve. 2019
• Zambon A et al, Vocal cord paralysis in Charcot-Marie-Tooth type 4B1 disease associated with a novel mutation in the myotubularin-related protein 2 gene: a case report and review of the literature. Neuromuscul Disord. 2017
• D'Amico A et al, Diagnosis of Duchenne Muscular Dystrophy in Italy in the last decade: critical issues and areas for improvements. Neuromuscul Disord. 2017
• Bolino A et al, Niacin-mediated Tace activation ameliorates CMT neuropathies with focal hypermyelination. EMBO Mol Med 2016
• Feltri ML et al, How Schwann cells sort axons. Neuroscientist. 2015
• Cossu G et al, Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne Muscular Dystrophy. Embo Mol Med 2015
• Domi T et al, Mesoangioblast delivery of miniagrin ameliorates murine model of Merosin Deficient Congenital Muscular Dystrophy type 1A. Skelet Muscle. 2015
• Porrello  et al, Jab1 regulates Schwann cell proliferation and axonal sorting through p27.J Exp Med. 2014
• Triolo D et al, Vimentin regulates peripheral nerve myelination. Development 2012
• Zimoń M et al, . Loss of function mutations in HINT1 are a major cause of peripheral neuropathy with neuromyotonia. Nat Genet. 2012
• Mazzone E et al, Longitudinal assessment of North Star Ambulatory Assessment and 6-minute walk in ambulant boys with Duchenne muscular dystrophy. Neurology 2011