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Updated: Oct 15, 2025
Induction of Complete Transection-Type Spinal Cord Injury in Mice
Published on: May 6, 2020
Selective Myostatin Inhibition Spares Sublesional Muscle Mass and Myopenia-Related Dysfunction after Severe Spinal
Gregory E Bigford1, Adriana Donovan2, Micah T Webster2
1Department of Neurological Surgery and the Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, USA.
Abstract:
Clinically relevant myopenia accompanies spinal cord injury (SCI), and compromises function, metabolism, body composition, and health. Myostatin, a transforming growth factor (TGF)β family member, is a key negative regulator of skeletal muscle mass. We investigated inhibition of myostatin signaling using systemic delivery of a highly selective monoclonal antibody - muSRK-015P (40 mg/kg) - that blocks release of active growth factor from the latent form of myostatin. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kdyn) at T9 and were then immediately and 1 week later administered test articles: muSRK-015P (40 mg/kg) or control (vehicle or IgG). A sham control group (laminectomy only) was included. At euthanasia, (2 weeks post-SCI) muSRK-015P preserved whole body lean mass and sublesional gastrocnemius and soleus mass. muSRK-015P-treated mice with SCI also had significantly attenuated myofiber atrophy, lipid infiltration, and loss of slow-oxidative phenotype in soleus muscle. These outcomes were accompanied by significantly improved sublesional motor function and muscle force production at 1 and 2 weeks post-SCI. At 2 weeks post-SCI, lean mass was significantly decreased in SCI-IgG mice, but was not different in SCI-muSRK-015P mice than in sham controls. Total energy expenditure (kCal/day) at 2 weeks post-SCI was lower in SCI-immunoglobulin (Ig)G mice, but not different in SCI-muSRK-015P mice than in sham controls. We conclude that in a randomized, blinded, and controlled study in mice, myostatin inhibition using muSRK-015P had broad effects on physical, metabolic, and functional outcomes when compared with IgG control treated SCI animals. These findings may identify a useful, targeted therapeutic strategy for treating post-SCI myopenia and related sequelae in humans.
Insights
Myostatin inhibition with muSRK-015P preserves muscle mass and improves function after spinal cord injury (SCI) in mice. This targeted therapy shows potential for treating muscle loss and related issues in humans following SCI.
Area of Science:
- Neuroscience
- Muscle Biology
- Pharmacology
Background:
- Spinal cord injury (SCI) often leads to clinically relevant myopenia, negatively impacting function, metabolism, and body composition.
- Myostatin, a member of the transforming growth factor (TGF)-β superfamily, is a critical negative regulator of skeletal muscle mass.
Purpose of the Study:
- To investigate the efficacy of systemic delivery of muSRK-015P, a monoclonal antibody inhibiting myostatin, in preserving muscle mass and function following SCI.
- To evaluate the impact of myostatin inhibition on myofiber characteristics, muscle phenotype, and metabolic parameters in SCI mice.
Main Methods:
- Adult female C57BL/6 mice underwent severe SCI (65 kdyn) at T9.
- Test articles, muSRK-015P (40 mg/kg) or control (vehicle or IgG), were administered immediately and 1 week post-SCI.
- Sham control group (laminectomy only) was included. Outcomes assessed at 2 weeks post-SCI included body composition, muscle mass, myofiber morphology, phenotype, motor function, and energy expenditure.
Main Results:
- muSRK-015P treatment preserved whole body lean mass and sublesional gastrocnemius and soleus muscle mass.
- Myofiber atrophy, lipid infiltration, and loss of slow-oxidative phenotype in soleus muscle were attenuated.
- Significant improvements in sublesional motor function and muscle force production were observed at 1 and 2 weeks post-SCI.
- Lean mass and total energy expenditure in muSRK-015P treated mice were comparable to sham controls, unlike SCI-IgG mice.
Conclusions:
- Systemic myostatin inhibition using muSRK-015P demonstrated broad beneficial effects on physical, metabolic, and functional outcomes in a mouse model of SCI.
- These findings suggest that myostatin inhibition is a promising therapeutic strategy for mitigating post-SCI myopenia and its associated complications in humans.
