2025-10-21 ミネソタ大学
University of Minnesota researchers developed a new type of therapy using a “bottlebrush polymer,” a highly branched synthetic molecule designed to protect muscle cell membranes from damage. Credit: University of Minnesota
<関連情報>
- https://cse.umn.edu/college/news/university-minnesota-research-team-discovers-new-therapy-potential-duchenne-muscular
- https://www.pnas.org/doi/10.1073/pnas.2513599122
合成ボトルブラシブロック共重合体がデュシェンヌ型筋ジストロフィーの発症を予防 Synthetic bottlebrush block copolymer prevents disease onset in Duchenne muscular dystrophy
Houda Cohen, Addeli Bez Batti Angulski, Joseph D. Quick, +10 , and Joseph M. Metzger
Proceedings of the National Academy of Sciences Published:October 13, 2025
DOI:https://doi.org/10.1073/pnas.2513599122
Significance
Advances in synthetic chemistry have led to an exciting class of polymers with an enormous range of molecular architectures featuring highly branched “bottlebrush” designs. A bottlebrush block copolymer (BB polymer) is identified here as a membrane stabilizer for the inherited muscle disease, Duchenne muscular dystrophy (DMD). Remarkably, this BB polymer is shown to be ~150,000 times more potent than the most effective linear triblock/diblock polymer membrane stabilizers. Furthermore, strikingly, delivery of the BB polymer in vivo is sufficient to prevent the onset of muscle damage and membrane leakiness in DMD animals. These findings reveal a connection between the branched molecular architecture in the mildly amphiphilic synthetic polymer and physiological action linked to interactions with lipid bilayers.
Abstract
Duchenne muscular dystrophy (DMD) is a fatal genetic disease of progressive muscle deterioration with no cure. DMD treatment requires a body-wide approach to target all diseased striated muscles: limb, respiratory, and heart. To address this, we focus studies on blocking the onset of muscle membrane instability, the primary defect in DMD, as a promising yet unmet druggable target. Here, data show the remarkable potency of a synthetic poly(ethylene oxide)/poly(propylene oxide) side chain–based bottlebrush block copolymer, ~150,000 times more potent than linear polymers, to rapidly restore contractile function to DMD skeletal muscle fibers in vitro. Strikingly, upon bottlebrush polymer delivery to DMD animals, results show highly efficacious prevention of the onset of skeletal and diaphragm muscle damage and the blocking of stress-induced cardiac injury and death in vivo. These data suggest bottlebrush polymers as a potent stand-alone muscle membrane-stabilizing therapeutic for DMD. Given DMD’s early childhood onset, together with newborn screening for DMD, bottlebrush macromolecules could be envisioned as an early therapy to preserve and protect viable muscle and potentially for other acquired or inherited diseases involving membrane damage.
