Research published in Science Advances found that safe and targeted delivery of nanoparticle (NP)-based anti-inflammatory cytokines initiates a specific T-cell response, thereby strengthening the muscles affected by Duchenne muscular dystrophy (DMD).
Inflammation plays a crucial role in disease progression in muscular dystrophies, a group of chromosomal disorders which lead to progressive loss of muscle mass and function. DMD is a severe such disorder that affects the entire body’s muscles, predominantly in boys. Researchers are pursuing various anti-inflammatory methodologies to prevent the degeneration of muscles in muscular dystrophy patients.
“Using NP-based cytokine delivery, we can create a therapeutic immune status in muscles affected by DMD that targets inflammation as a universal driver of the disease,” said David Mooney, PhD, who leads the Wyss Institute for Biologically Inspired Engineering’s Immuno-Materials Platform and is also the Robert P. Pinkas Family Professor of Bioengineering at Harvard University’s John A. Paulson School of Engineering and Applied Sciences, Boston, Massachusetts.
To study the outcome of NPs carrying inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) on DMD-affected muscles, the investigators used a mouse model known as Mdx that carries a particular DMD mutation found in humans. Muscle degeneration happens much slower in Mdx mice than in human patients. Because of this, a microinjury approach was created whereby the posterior limbs of aged Mdx mice were continually wounded to speed up the murine disease progression, which closely mirrors the human disease.
After concluding a weeklong microinjury procedure, IL-4 and IL-10 NPs were injected directly into the severely injured muscle, and results were evaluated after 2 weeks. “Cytokine therapy with IL-4 but not IL-10 conjugated to NPs significantly increased the area in cross-sections covered by muscle fibers and, in living animals, the treated muscles showed a four-fold increase in contraction force and speed (velocity) compared to mice in control groups,” said Theresa Raimondo, PhD, who performed the work as a graduate student in Dr. Mooney’s group.
Dr. Raimondo also added that “interestingly, we could chalk up the regenerative effects to a specific increase in regulatory T cells (Tregs), an immunosuppressive T cell type that was known to counteract inflammatory processes in muscles weakened by DMD.”
The methodology developed by Dr. Mooney’s group could be developed as an alternate treatment for curing patients with DMD whose loss of muscle mass and function cannot be efficiently prevented by any other means.
Muscling up with nanoparticle-based anti-inflammatory therapy. News release. WYSS Institute for Biologically Inspired Engineering at Harvard University; June 24, 2021Raimondo TM, Mooney DJ.
Anti-inflammatory nanoparticles significantly improve muscle function in a murine model of advanced muscular dystrophy. Sci Adv. 2021;7(26):eabh3693. doi:10.1126/sciadv.abh3693