TY - CHAP
T1 - Systemic Delivery of a Monoclonal Antibody to Immunologically Block Myostatin in the A17 Mouse Model of OPMD
AU - Malerba, Alberto
AU - Harish, Pradeep
AU - Popplewell, Linda
N1 - © 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/11/19
Y1 - 2022/11/19
N2 - Oculopharyngeal muscular dystrophy (OPMD) is a late-onset rare muscle disease affecting approximately 1 in 80,000 individuals worldwide. However, it can affect as much as 1:600 individuals in some populations due to a strong founder effect. The muscle pathology is characterized by progressive eyelid drooping (ptosis), swallowing difficulties (dysphagia), and limb weakness at later stages of disease progression. The genetic defect is associated with significant fibrotic deposition and atrophy in affected muscles. No treatments are available to cure the disease. Only surgical techniques to correct ptosis and swallowing are currently possible, though they carry a risk of recurrence. Myostatin is a negative regulator of muscle growth, and several strategies to downregulate its expression have been developed with the aim of improving muscle mass and strength in muscular pathologies. We recently showed that weekly systemic treatment of the A17 murine model of OPMD with a monoclonal antibody for myostatin improves body and muscle mass, increases muscle strength, and reduces muscle fibrosis. Here, we describe the methodology for repeated intraperitoneal delivery of myostatin antibody in the murine model. Furthermore, we detail the most relevant analyses to assess histopathological and functional improvements of this treatment in this mouse model.
AB - Oculopharyngeal muscular dystrophy (OPMD) is a late-onset rare muscle disease affecting approximately 1 in 80,000 individuals worldwide. However, it can affect as much as 1:600 individuals in some populations due to a strong founder effect. The muscle pathology is characterized by progressive eyelid drooping (ptosis), swallowing difficulties (dysphagia), and limb weakness at later stages of disease progression. The genetic defect is associated with significant fibrotic deposition and atrophy in affected muscles. No treatments are available to cure the disease. Only surgical techniques to correct ptosis and swallowing are currently possible, though they carry a risk of recurrence. Myostatin is a negative regulator of muscle growth, and several strategies to downregulate its expression have been developed with the aim of improving muscle mass and strength in muscular pathologies. We recently showed that weekly systemic treatment of the A17 murine model of OPMD with a monoclonal antibody for myostatin improves body and muscle mass, increases muscle strength, and reduces muscle fibrosis. Here, we describe the methodology for repeated intraperitoneal delivery of myostatin antibody in the murine model. Furthermore, we detail the most relevant analyses to assess histopathological and functional improvements of this treatment in this mouse model.
UR - http://www.scopus.com/inward/record.url?scp=85142401957&partnerID=8YFLogxK
U2 - 10.1007/978-1-0716-2772-3_30
DO - 10.1007/978-1-0716-2772-3_30
M3 - Chapter
C2 - 36401050
AN - SCOPUS:85142401957
SN - 9781071627716
VL - 2587
T3 - Methods in Molecular Biology
SP - 557
EP - 568
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -