Starving Inflammatory Immune Cells Slows Damage Caused By Multiple Sclerosis

Using a mouse model of multiple sclerosis (MS), researchers at the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences demonstrated that immune cells utilize fatty acids as their energy source to limit MS disease progression. The findings are published in a paper in the journal Scientific Reports.

MS is caused when the protective myelin sheath surrounding the nerve cells is damaged by the body’s own immune cells. This causes the nerve impulses to slow down or halt, resulting in progressive physical and neurological disabilities.

First author Leah P. Shriver, PhD, and Marianne Manchester, PhD, professor of pharmacy examined the process by which immune cells in the CNS oxidize fatty acids for energy in the shortage of glucose, a condition seen in inflamed tissues.
Using a mouse model that imitated chronic MS, Manchester and Shriver discovered that the restriction of a single enzyme that helps fatty acid utilization by immune cells caused cell starvation and death, thus preventing further inflammatory damage.

Presently, there are no established drugs or therapies that target fatty acid metabolism in MS. Moreover, treatment specificity involving single enzyme inhibition is very unlikely to cause any adverse side effects such as increased infection.

Shriver said, “We expect that because immune cells not in lesions in the CNS are able to use available glucose, they will function just fine during infection and that inhibition of this pathway would not produce general immune suppression.”

In their study, Manchester and Shriver used an enzyme-inhibitor drug that is already tested in and tolerated by individuals with congestive heart failure. Using mass spectrometry, scientists are now trying to understand whether the mouse model results could be translated in humans.
Manchester said, “We are interested in determining how this pathway is utilized in human tissue samples from MS patients.”

The National Institutes of Health and the National Institute of Neurological Disorders and Stroke funded this study.

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