Researchers found that the purified form of a burnt sugar derivative, when given in appropriate doses, improved the muscle regeneration in a mouse model of Duchenne muscular dystrophy.
The researchers from the University of Washington explained that the mice in their study, like boys with the gender-linked inherited disorder, are missing the gene that produces dystrophin, a muscle-repair protein.
AdvertisementProfessor of biochemistry and associate director of the Institute for Stem Cell and Regenerative Medicine, Hannele Ruohola-Baker's lab originally identified the sphingosine 1-phosphate (S1P) pathway as a critical player in ameliorating muscular dystrophy in flies.
Reyes said that the multi-talented, bioactive lipid is essential in turning stem cells into specific types of cells, in regenerating damaged tissue, and in inhibiting cell death. Without cell receptors for sphingosine 1-phosphate, an embryo would fail to develop.
Other scientists had observed that levels of sphingosine 1-phosphate are lower in the muscles of mice with the muscular dystrophy mutation, and that certain cell repair pathways involving this signal are impaired.
By using insect activity monitors, the scientists assessed the effects of drug and gene therapy candidates on the flies' ability to move.
This screening tool led to the discovery that a small molecule with a long name, 2-acetyl4 (5)-tetrahydroxybutyl imidazole, or THI for short, blocks an enzyme that breaks down sphingosine 1-phosphate.
The substance is also found in very tiny amounts in burnt sugar, brown sugar, beer, cola and some candies.
They confirmed that the THI alleviated muscle wasting in the flies. A few other drugs, including a THI derivative and an unrelated drug now in clinical trials for rheumatoid arthritis, also showed beneficial effects in fruit flies.
Researchers than treated old dystrophic mice with direct injection of THI.
"We observed that treatment with THI significantly increased muscle fiber size and muscle-specific force in our affected mice," Reyes said.
"We also saw that other hallmarks of impaired muscle regeneration - fat deposits and fibrosis [scar tissue] accumulation - were also lower in the THI-treated mice," she said.
The research is published in the journal Skeletal Muscle.