title: Intracerebroventricular Delivery in Mice for Motor Neuron Diseases.
abstract: The use of antisense oligonucleotides to target specific mRNA sequences represents a promising therapeutic strategy for neurological disorders. Recent advances in antisense technology enclose the development of phosphorodiamidate morpholino oligomers (MO), which is one of the best candidates for molecular therapies due to MO's excellent pharmacological profile.Nevertheless, the route of administration of antisense compounds represents a critical issue in the neurological field. Particularly, as regards motor neuron diseases, intracerebroventricular (ICV) injection is undoubtedly the most efficient procedure to directly deliver therapeutic molecules in the central nervous system (CNS). Indeed, we recently demonstrated the outstanding efficacy of the MO antisense approach by its direct administration to CNS of the transgenic mouse models of Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS).Here, we describe methods to perform the ICV delivery of MO in neonatal SMA mice and in adult ALS mice.
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, and Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, 20122, Milan, Italy. monica.nizzardo1@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Nizzardo
authors.affiliation: Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, and Neurology Unit, IRCCS Foundation Ca' Granda, Ospedale Maggiore Policlinico, 20122, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rizzuti
mesh_terms: D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000628:therapy; D000818:Animals; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D056426:Genetic Loci; D015316:Genetic Therapy; D057967:Infusions, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D060172:Morpholinos / Q000008:administration & dosage* / Q000235:genetics*; D016472:Motor Neuron Disease / Q000235:genetics* / Q000628:therapy; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D000072105:Superoxide Dismutase-1 / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
chemical_list: D060172:Morpholinos; D055540:Survival of Motor Neuron 2 Protein; D000072105:Superoxide Dismutase-1
keywords: Adult mice; Amyotrophic lateral sclerosis; Intracerebroventricular injection; Morpholino; Motor neuron diseases; Neonatal mice; Spinal muscular atrophy