Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.
While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Rebecca M
RM
Heidker
Department of Pharmaceutical Sciences, College of Pharmacy-Glendale, Midwestern University, Glendale, AZ 85308, USA.
Mitchell R
MR
Emerson
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Steven M
SM
LeVine
D001710:Biotin / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D002784:Cholesterol / Q000378:metabolism; D005502:Food / Q000009:adverse effects; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009751:Nutritional Requirements; D009836:Oligodendroglia / Q000187:drug effects*; D015398:Signal Transduction; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D014803:Vitamin B Complex; D006418:Heme; D001710:Biotin; D002784:Cholesterol; D007501:Iron