biostudies-literatureShababi MNational Institute of Neurological Disorders and StrokeNINDS NIH HHSNational Institutes of Health348-360https://www.ebi.ac.uk/biostudies/studies/S-EPMC6127875biostudies-literatureUnknown10Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an infantile autosomal recessive disease caused by the loss of the ubiquitously expressed <i>IGHMBP2</i> gene. SMARD1 causes degeneration of alpha-motor neurons, resulting in distal muscle weakness, diaphragm paralysis, and respiratory malfunction. We have reported that delivery of a low dose of AAV9-<i>IGHMBP2</i> to the CNS results in a significant rescue of the SMARD1 mouse model (<i>nmd</i>). To examine how a delivery route can impact efficacy, a direct comparison of intravenous (IV) and intracerebroventricular (ICV) delivery of AAV9-<i>IGHMBP2</i> was performed. Using a low-dose, both IV and ICV delivery routes led to a significant extension in survival and increased body weight. Conversely, only ICV-treated animals Molecular therapy. Methods & clinical developmentA Direct Comparison of IV and ICV Delivery Methods for Gene Replacement Therapy in a Mouse Model of SMARD1.PMC6127875R21 NS093175R21NS093175DeMarco VLorson CLKaifer KAShababi MVillalon EfalseA Direct Comparison of IV and ICV Delivery Methods for Gene Replacement Therapy in a Mouse Model of SMARD1.Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an infantile autosomal recessive disease caused by the loss of the ubiquitously expressed <i>IGHMBP2</i> gene. SMARD1 causes degeneration of alpha-motor neurons, resulting in distal muscle weakness, diaphragm paralysis, and respiratory malfunction. We have reported that delivery of a low dose of AAV9-<i>IGHMBP2</i> to the CNS results in a significant rescue of the SMARD1 mouse model (<i>nmd</i>). To examine how a delivery route can impact efficacy, a direct comparison of intravenous (IV) and intracerebroventricular (ICV) delivery of AAV9-<i>IGHMBP2</i> was performed. Using a low-dose, both IV and ICV delivery routes led to a significant extension in survival and increased body weight. Conversely, only ICV-treated animals 2018-01-01T00:00:00Z2018 Sep2026-05-05T20:37:23.644Z2019-03-26T23:55:28ZS-EPMC61278753020277210.1016/j.omtm.2018.08.005