In their report titled "Statin Therapy Inhibits Remyelination in the Central Nervous System" Miron and others must have startled those who once considered statin therapy appropriate for multiple sclerosis. In the American Journal of Pathology, Vol. 174, No. 5, May 2009, Veronique Miron presented data that has sent proponents of simvastatin treatment for multiple sclerosis back to their drawing boards.
Characterized by inflammatory demyelinating lesions in the central nervous system, multiple sclerosis (MS) has been propelled into clinical trials by earlier studies of the use of simvastatin. Not so, reports Miron! These earlier short-term studies that showed possible benefit from simvastatin (Zocor®) use could not be confirmed in their longer-term studies. The short-term studies involved the effect of simvastatin on cell cultures of oligodendroglia progenitor cells (OPCs).
Mature oligodendrocytes (the glial cells I have spoken of many times previously) are the primary producers of cholesterol in the brain and throughout the central nervous system. Cholesterol is highly concentrated in oligodendroglial membranes and undergoes a continuous turnover in myelin sheaths surrounding, and thereby insulating, the nerves. Cholesterol is also concentrated in fluid microdomains in the membrane bilayer, termed lipid rafts, which house and, with the help of dolichols, aggregate signaling molecules to facilitate the initialization of intracellular signaling cascades (translation: trigger cell signalling.)
Simvastatin, a so-called blood brain barrier statin because of its lipophilic tendency, not only restricts the synthesis of the cholesterol needed in all these structures but also restricts the synthesis of dolichols (isoprenoids) that determine subsequent lipid attachments.
These researchers demonstrated that simvastatin interferes with myelin repair and maintenance by directly impacting OPC functions and affecting mature glial cell numbers. Animal studies have revealed that simvastatin inhibits the migration of progenitor cells into the MS lesion as well as their differentation into mature glial cells.
The team concluded, "Together, our data support the conclusion that simvastatin blocks the differentiation of progenitors into mature myelinating cells, thereby inhibiting remyelination in our MS model. We also show the importance of cholesterol and dolichol synthesis pathways in the processes of myelin maintenance and remyelination."
From the beginning of my research into the effects of reductase inhibitors I have stressed the inevitability of mevalonate blockade. That is what statins were designed to do - inhibition of cholesterol via blockade of its synthesis pathway. This must inevitably be associated with inhibition of all other vital processes carried in this pathway, of which dolichols is particularly relevant to this discussion.
And now, nearly 18 years from the beginning of statin marketing, we have well-meaning research teams still confused about the effects of simvastatin. They actually thought it might have some use in treatment of multiple sclerosis when in reality the effects of this statin, if anything, is to create changes favoring this MS process. By now research scientists should have known of these effects of statins. Bottom line: yes, statin use can be associated with multiple sclerosis.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor