Our nervous system relies on electrical signals to control how our muscles move. Nerves are insulated and supported by a coating called myelin. In multiple sclerosis (MS), the immune system erroneously attacks the myelin sheath of neurons, disrupting the electrical signals and by extension, the movement of muscles. The symptoms of the disease are widely varied; some people may have periods of remission while others lose the ability to walk.
Current MS treatments may disrupt the progression of the disease but they must be used early enough. New research has identified a compound that is present in fruit peels that could reduce the nerve damage that happens in MS. This compound, which can be found in apple and prune peels and some herbs, might help develop the first treatment that could reverse the damage caused by MS. The findings have been reported in the Proceedings of the National Academy of Sciences (PNAS).
"Although the evidence is preliminary - our data is from animal models of disease - it's encouraging to see a compound that both halts and repairs damage in MS in the lab," said the co-senior study author Guang-Xian Zhang, PhD, Professor of Neuroscience at the Sidney Kimmel Medical College at Thomas Jefferson University.
"There is additional work we must do to test the safety of this compound, ursolic acid" said the co-senior study author A.M. Rostami, MD, PhD, chair of the Department of Neurology at the Vickie and Jack Farber Institute for Neuroscience - Jefferson Health. "But this is a great new lead for disease treatment."
In this work, the scientists developed a mouse model of MS that mimics the human disease; it slowly progresses over the life of the mouse. The acute phase begins around day twelve, when partial paralysis sets in. These mice were exposed to ursolic acid, but not until day 60, well into the course of the disease and after tissue damage has occurred in the brain and spinal cord.
"Many experiments have looked at mice in the acute phase, when disease is just starting or at the peak," said Dr. Zhang. "Instead, we tested whether this compound was effective in chronic disease, once there has already been chronic damage to tissues of [the] central nervous system."
After twenty days of treatment, the mice began to show signs of improvement. The mice that started out paralyzed began to walk again (though weakly) after treatment, which continued for sixty days.
"It's not a cure, but if we see a similar response in people, it would represent a significant change in quality of life. And most significantly, it's a reversal, which we really haven't seen before with other agents at such a late stage of disease," said Dr. Zhang.
The scientists also assessed how ursolic acid affected immune cells called Th17, a known driver of the autoimmune response seen in MS. The molecule was able to trigger the differentiation of precursor cells into cells that make myelin in the central nervous system, called oligodendrocytes.
"This maturation effect is the most crucial," said Dr. Zhang. "Myelin-sheath-making oligodendrocytes are depleted in MS. And the stem cells that produce new oligodendrocytes are dormant and unable to mature. This compound helps activate those stem cells into making new oligodendrocytes, and is likely responsible for the reversal of symptoms we saw."
Ursolic acid first has to be tested for safety. Though it's used as a dietary supplement, high doses may be dangerous.
"There are still a number of tests to complete before the first clinical trials," said Dr. Rostami. "However, we are moving quickly with this promising approach."
Sources: AAAS/Eurekalert! via Thomas Jefferson University, Proceedings of the National Academy of Sciences
