Regenerating Muscle in Duchenne Muscular Dystrophy: Age Matters

Contact Information

Available for logged-in reporters only

Newswise LA JOLLA, Calif., April 11, 2014 A team of scientists led by Pier Lorenzo Puri, M.D., associate professor at Sanford-Burnham Medical Research Institute (Sanford-Burnham), in collaboration with Fondazione Santa Lucia in Rome, Italy, have published details of how a class of drugs called HDACis drive muscle-cell regeneration in the early stages of dystrophic muscles, but fail to work in late stages. The findings are key to furthering clinical development of HDACis for Duchenne muscular dystrophy (DMD), an incurable muscle-wasting disease.

A symphony to rebuild muscle

The research, to be published April 15 in Genes and Development, used mouse models of DMD to show how fibro-adipogenic progenitor cells (FAPs) act like orchestra conductors in the music of muscle regeneration. FAPs sit in the space between muscle fibers and coordinate a complex symphonyreceiving the notes that muscle has been damaged and directing muscle stem cellssatellite cellsto rebuild muscle.

HDACis create an environment conducive for FAPs to direct muscle regenerationbut only during the early stages of DMD progression in mice, said Puri. At some point, DMD progresses to a pathological point of no return and become permanently resistant to muscle-regeneration cures and to HDACis. HDACis open the blueprints for muscle regeneration

HDACis stands for histone deacetylase inhibitors. They are epigenetic drugs that work by facilitating the accessibility to the genes that code for muscle proteins by the cell machinery that transcribes the genetic code into proteins. In essence, HDACis open the blueprints for protein manufacturing and instruct FAPs to support muscle regeneration.

In normal wear and tear, FAPs direct stem cells within the muscle to regenerate and repair damaged muscle. In DMD, the persistent breakdown of muscle cells creates an environment in such disarray that FAPs ability to direct muscle regeneration is compromisedlike trying to conduct a symphony with punk rock music in the background.

Collaborating to find a treatment for DMD

Puri, along with his Italian colleagues at Fondazione Santa Lucia, Italfarmaco, and Parent Project Muscular Dystrophy, an advocacy association, are currently developing HDACis for the treatment of DMD a clinical trial with DMD boys is currently ongoing.

Follow this link:
Regenerating Muscle in Duchenne Muscular Dystrophy: Age Matters