The therapeutic potential of soluble activin type IIB receptor treatment in a limb girdle muscular dystrophy type 2D mouse model

Alqallaf, A., Engelbeen, S., Palo, A., Cutrupi, F., Tanganyika-de Winter, C., Plomp, J., Vaiyapuri, S. ORCID: https://orcid.org/0000-0002-6006-6517, Aartsma-Rus, A., Patel, K. and Putten, M. v. (2022) The therapeutic potential of soluble activin type IIB receptor treatment in a limb girdle muscular dystrophy type 2D mouse model. Neuromuscular Disorders, 32 (5). pp. 419-435. ISSN 0960-8966 doi: 10.1016/j.nmd.2022.03.002

Abstract/Summary

Limb girdle muscular dystrophy type 2D (LGMD2D) is characterized by progressive weakening of muscles in the hip and shoulder girdles. It is caused by a mutation in the α-sarcoglycan gene and results in absence of α-sarcoglycan in the dystrophin-glycoprotein complex. The activin type IIB receptor is involved in the activin/myostatin pathway, with myostatin being a negative regulator of muscle growth. In this study, we investigated the effects of sequestering myostatin by a soluble activin type IIB receptor (sActRIIB) on muscle growth in Sgca -null mice, modelling LGMD2D. Treatment was initiated at 3 weeks of age, prior to the disease onset, or at 9 weeks of age when already in an advanced stage of the disease. We found that early sActRIIB treatment resulted in increased muscle size. However, this led to more rapid decline of muscle function than in saline-treated Sgca -null mice. Furthermore, no histopathological improvements were seen after sActRIIB treatment. When initiated at 9 weeks of age, sActRIIB treatment resulted in increased muscle mass too, but to a lesser extent. No effect of the treatment was observed on muscle function or histopathology. These data show that sActRIIB treatment as a stand-alone therapy does not improve muscle function or histopathology in Sgca -null mice.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/104798
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	Elsevier
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