Multiple sclerosis (MS) has long been considered a chronic, inflammatory disorder of the central white matter in the brain that causes demyelination (damage to the protective covering that surrounds nerve fibers in the brain and spinal cord). Now increasingly viewed as a neurodegenerative disorder, researchers believe the inflammation and demyelination seen in the disease may be caused by abnormalities in mitochondrial dynamics that impact cellular pathways and lead to axonal injury, neuronal loss, and atrophy of the central nervous system. This has led some scientists to wonder, “Is multiple sclerosis a mitochondrial disease?”
While all of our systems are dependent on the energy output of mitochondria, the brain and nervous system are especially dependent on healthful energy metabolism. Defective mitochondrial metabolism may generate more reactive oxygen species (ROS) that can increase oxidative stress and be damaging to cells. This energy failure is now viewed as a key player in the pathogenesis of multiple sclerosis. Speaking at a recent workshop titled, “Metabolism in MS and Related Conditions,” Dr. David Sheikh-Hamad, professor of medicine-nephrology at Baylor College of Medicine, reported that evidence exists that oxidative stress is a primary contributor to neuronal death in neurodegenerative and neuroinflammatory disorders (including MS).”
In an article, “Is Multiple Sclerosis a Mitochondrial Disease?” published in Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, Dr. Peizhong Mao and Dr. P. Hemachandra Reddy, of the Neurogenetics Laboratory at Oregon Health & Science University, identified five key mitochondrial abnormalities that are involved in disease development and progression. Mitochondrial DNA defects, abnormal mitochondrial gene expression, defective mitochondrial enzyme activities, deficient mitochondrial DNA repair activity, and mitochondrial dysfunction have been shown to play a role.
Causal factors of this complicated disease are still unknown. However, given the central role of the mitochondria in many important cellular functions researchers continues to look at mitochondrial dysfunction as the key contributor to neurodegenerative process of this disease.
Targeting repair proteins to the mitochondria may prove to be an effective means for treating multiple sclerosis, while also addressing the direct problem of mitochondrial dysfunction in the disease.The use of mitochondria-targeted antioxidants that combat oxidative stress may help reduce the development of multiple sclerosis. In a 2015 clinical study, Coenzyme Q10 supplementation ameliorated inflammatory markers in patients with relapsing-remitting MS. A subsequent 2016 study showed a significant improvement of fatigue in patients with multiple sclerosis.
The antioxidant, lipoic acid, has also been proposed as a therapeutic treatment for MS. Studies have linked lipoic acid to decreased inflammation, as well as decreased optic nerve and spinal cord atrophy in mouse models and a significant reduction in brain atrophy with an increased walking speed and a decrease in the number of falls in a study of patients with secondary-progressive multiple sclerosis.
Enhancing mitochondrial repair may eventually prove to be an effective treatment for multiple sclerosis and improve the quality of life for those suffering from the disease.