Poloxamer [corrected] 188 has a deleterious effect on dystrophic skeletal muscle function

Area of Science:

• Biomedical Engineering
• Muscle Physiology
• Pharmacology

Background:

• Duchenne muscular dystrophy (DMD) is a fatal genetic disorder with no cure.
• Poloxamer 188 (P188) has shown promise for DMD-related cardiomyopathy.
• Skeletal muscle effects of P188 in DMD are not well understood.

Purpose of the Study:

• To investigate the impact of Poloxamer 188 (P188) on dystrophic skeletal muscle function in mdx mice.
• To assess P188's effects on contraction-induced injury and muscle force production.

Main Methods:

• Mdx mice received daily intraperitoneal injections of P188 (30 or 460 mg/kg) or saline for two weeks.
• In situ muscle function tests were performed on the Tibialis Anterior (TA) muscle.
• Tests included force-frequency relationships and eccentric contraction protocols.

Main Results:

• Two weeks of P188 treatment significantly increased susceptibility to contraction-induced injury in mdx mouse TA muscle.
• No significant changes were observed in the force-frequency relationship or maximum isometric specific force.
• P-value for increased injury was < 0.0001.

Conclusions:

• P188 treatment exacerbates skeletal muscle injury in the context of Duchenne muscular dystrophy.
• The therapeutic potential of P188 for DMD requires re-evaluation, particularly concerning skeletal muscle.
• Findings highlight the need for targeted therapies addressing skeletal muscle pathology in DMD.