Oral Farnesol Administration Protects Against Inflammatory Demyelination

Farnesol (FOL) is a naturally-produced 15-carbon organic acyclic sesquiterpene alcohol (isoprenol) that acts as a potent blocker of neuronal voltage-gated Ca ²⁺ channels (L- and N-type) and is found in the human brain. FOL has potent anti-oxidant and anti-inflammatory effects in vitro and is neuroprotective in a murine model of neurotoxicity. Because inflammation and neurodegeneration are mechanisms associated with CNS demyelinating diseases, we sought to determine whether FOL treatment would result in protection against experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We compared the progression of EAE in MOG _35-55 immunized female C57BL/6 mice treated orally with FOL (100 mg/kg/daily) emulsified in corn oil, versus vehicle-treated and untreated EAE mice. Unexpectedly, FOL did not confer protection against EAE as previously seen in experiments in our lab. Prompted by this result, gas chromatography mass spectrometry (GC-MS) was performed on our lab’s FOL and a newly ordered one, which resulted in the detection of unexpected peaks consistent with auto-oxidation products of FOL by reaction with atmospheric oxygen. In another EAE experiment with the newly ordered FOL, FOL significantly reduced the average clinical scores of EAE mice when compared to untreated mice and vehicle-treated mice. Although FOL’s protective mechanism of action remains to be known, we propose that FOL promotes protection against CNS inflammatory demyelination by promoting an anti-inflammatory effect. We demonstrate that there is a correlation between EAE severity and FOL oral treatment. Understanding the neuroprotective effects of FOL may provide insight into novel therapeutic approaches for MS.