Motoneuron Transplantation Rescues the Phenotype of SMARD1 (spinal Muscular Atrophy with Respiratory Distress Type 1)

Overview

Journal J Neurosci

Specialty Neurology

Date 2009 Sep 25

PMID 19776263

Citations 19

Authors

Stefania Corti

Monica Nizzardo

Martina Nardini

Chiara Donadoni

Sabrina Salani

Roberto Del Bo

Dimitra Papadimitriou

Federica Locatelli

Nicoletta Mezzina

Francesca Gianni

Nereo Bresolin

Giacomo P Comi

Affiliations

Soon will be listed here.

Abstract

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal form of infantile motoneuron disease. There is currently no effective treatment, although motor neuron replacement is a possible therapeutic strategy. We transplanted purified motor neurons into the spinal cord of nmd mice, an animal model of SMARD1. We also administered pharmacological treatment targeting the induction of axonal growth toward skeletal muscle target. At the end stage of the disease, donor-derived motor neurons were detected in the nmd anterior horns, extended axons into the ventral roots, and formed new neuromuscular junctions. These data correlated with improved neuromuscular function and increased life spans. The neuroprotective effect was associated with a reduction in proinflammatory molecules in treated spinal cords. This is the first report that functional restoration of motor units with transplanted motoneurons is feasible in an animal model of a human motoneuron disease, opening up new possibilities for therapeutic intervention.

Citing Articles

Disease Mechanisms and Therapeutic Approaches in SMARD1-Insights from Animal Models and Cell Models.

Jablonka S, Yildirim E Biomedicines. 2024; 12(4).

PMID: 38672198 PMC: 11048220. DOI: 10.3390/biomedicines12040845.

Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1).

Perego M, Galli N, Nizzardo M, Govoni A, Taiana M, Bresolin N Cell Mol Life Sci. 2020; 77(17):3351-3367.

PMID: 32123965 PMC: 11104977. DOI: 10.1007/s00018-020-03492-0.

Spinal muscular atrophy with respiratory distress type 1: Clinical phenotypes, molecular pathogenesis and therapeutic insights.

Saladini M, Nizzardo M, Govoni A, Taiana M, Bresolin N, Comi G J Cell Mol Med. 2019; 24(2):1169-1178.

PMID: 31802621 PMC: 6991628. DOI: 10.1111/jcmm.14874.

Advances, Challenges, and Perspectives in Translational Stem Cell Therapy for Amyotrophic Lateral Sclerosis.

Abati E, Bresolin N, Comi G, Corti S Mol Neurobiol. 2019; 56(10):6703-6715.

PMID: 30911936 DOI: 10.1007/s12035-019-1554-x.

Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy.

Boido M, Vercelli A Front Neuroanat. 2016; 10:6.

PMID: 26869891 PMC: 4737916. DOI: 10.3389/fnana.2016.00006.

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