Researchers have discovered that a trace substance found in caramelized sugar and cola improves regeneration in mice suffering from Duchenne muscular dystrophy (DMD).
Scientists from the Reyes and Ruohola Baker laboratories at the University of Washington discovered that when the sugar substance, a small molecule called 2-acetyl-4(5)-tetrahydroxybutyl imidazole (THI), was injected into mice suffering from the muscular disease, muscle regeneration was improved.
The study, published in the journal Skeletal Muscle, tested mice that were missing the gene that produces dystrophin - a muscle repair protein. This is the same gene that is missing in boys suffering from DMD.
Muscular dystrophy is a term for a number of hereditary, progressive degenerative muscle disorders. It affects skeletal muscles and can often affect other organ systems.
DMD is the most common form of the disorder, mainly affecting boys, and onset of the disorder is usually between 3 and 5 years of age.
The disorder can progress rapidly, meaning that the majority of boys are unable to walk by the age of 12, and they eventually have to use a respirator to breathe.
According to the researchers, even with ventilator assistance to help DMD sufferers breathe, it is likely patients will not survive past the age of 30.
Currently, there is no cure for the disorder, but the symptoms can be relieved using the corticosteroid drug prednisone. However, the medicine can sometimes produce severe side effects.
Initial experiment on fruit flies
Prior to experimenting on the mice, the researchers discovered that a "pathway" in fruit flies, called sphingosine 1-phosphate (S1P), is critical in improving the effects of muscular dystrophy in the insects.
The researchers say that the S1P pathway is found in most living mammals and that it is essential in changing stems cells into specific types of cells, as well as inhibiting cell death and regenerating damaged tissue.
Scientists had previously discovered that levels of S1P are lower in the muscles of mice who have muscular dystrophy mutation, and they found that specific cell repair pathways are broken. But the study authors add that S1P could not be administered as a drug because the body uses it up too quickly.
The researchers wanted to see whether they could stop the naturally occurring S1P from degrading in the body.
Flies with the genetic defect usually fly around normally after they hatch, but eventually muscle degeneration leaves them flightless, the researchers say. They analyzed whether drugs and gene therapy would affect the flies' ability to move using insect activity monitors.
Muscle regeneration from substance found in cola
The researchers then discovered that the small molecule, 2-acetyl-4(5)-tetrahydroxybutyl imidazole (THI), can block the enzyme that breaks down S1P.
THI is found in:
- Caramelized sugar
- brown sugar
- And even some candles.
Upon this discovery, the researchers tested the molecule on mice with muscular dystrophy by directly injecting THI into their muscles and then adding the molecule into their drinking water.
When injected with the molecule, the mice showed significantly improved muscle regeneration.
Morayma Reyes, professor of pathology and laboratory medicine at the University of Washington, explains:
We observed that treatment with THI significantly increased muscle fiber size and muscle-specific force in our affected mice. 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."
Prof. Reyes adds: "It's interesting to note that THI is a trace component of Caramel Color III, which the US Food and Drug Administration categories as 'generally recognized as safe.'"
The researchers note that they linked the regenerative effects in the mice to the response of muscle-forming cells and the regrowth of muscle fibers.
A type of S1P and cell receptors for it were found in the cells of the regenerating muscle fibers, meaning that S1P increased the "regulators for the biochemical pathways that mediate skeletal muscle mass and muscle function."
The researchers conclude that they hope to conduct further studies on THI and other substances that could protect the body's supply of S1P that encourages muscle cell regeneration.
They add that as THI continues to show success against muscular dystrophy, pre-clinical studies of safety and effectiveness will be conducted before advancing to human trials.