High-dose statin therapy reduces brain atrophy in Secondary Progressive MS, new study finds
Headlines regarding the use of statins, or cholesterol-lowering drugs, in multiple sclerosis has once again hit the newsstands after The Lancet published results from a new study on March 19, 2014. In the current study, “Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial,” researchers noted a 43% reduced annualized rate of brain atrophy in SPMS patients taking 80mg simvastatin vs placebo over a 2-year time period (Chataway, 2014). This study appears to be the first conducted specifically in SPMS, a form of the disease which is characterized more by brain atrophy than RRMS which involves primarily CNS inflammation.
For the past decade, small preliminary studies have suggested that statins may be helpful as a disease-modifying treatment or add-on therapy for patients living with MS or those who have experienced a first neurological event. Early results were promising and suggest that MS patients who also take statins have less nerve damage over time. A study in 64 patients with acute optic neuritis showed that simvastatin improved visual outcomes (Tsakiri, 2012). Researchers have demonstrated that statin drugs, such as simvastatin, inhibit IL-17 cytokines and Th17 cell differentiation in patients with MS (Zhang, 2008, 2011, 2013). Other research has demonstrated that lovastatin can be used to regulate vitamin D metabolism and improve vitamin D3 efficacy in animal models of MS (Paintlia, 2012) which may have implications for future clinical research.
Statins as Add-On Therapy in RRMS:
However, beginning with a small study in 2008, MS patients treated with atorvastatin (Lipitor) seemed to get worse. Ten of the 17 patients who received either 40 mg or 80 mg of atorvastatin had either a relapse or a new lesion on MRI as compared to only 1 of 9 patients taking placebo who experienced a relapse or had active lesions on MRI. Authors concluded that atorvastatin (40 mg or 80 mg) taken with interferon beta-1a (Rebif) worsened MS (Lock, 2008).
A study involving 77 patients found that 40mg atorvastatin in addition to interferon beta-1b (Betaseron) did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month period (Kamm, 2012). In a larger placebo-controlled, double-blind, randomized study involving 307 patients found no beneficial effect of adding 80mg simvastatin to interferon beta-1a (Avonex) vs placebo. In fact, disease measures such as annualized relapse rate, time to first relapse, and number of new or enlarging T2 lesions were slightly worse (Sorensen, 2011). A retrospective study found that disability progression did not differ significantly between MS patients using statin therapy vs controls. Researchers found that statins, in doses currently prescribed for lowering cholesterol, do not affect the long-term course of MS (Paz Soldán, 2012).
In vitro studies have revealed that high-dose add-on statin therapy significantly reduces interferon-beta function and inhibits the effectiveness of interferon beta-1 therapies in RRMS patients (Feng, 2012). Post hoc analysis of patients in the SENTINEL trial indicated that statin therapy did not appear to affect the clinical effects of interferon beta-1a (Avonex) in patients with RRMS (Rudick, 2009) and early studies supported the safety and efficacy of simvastatin in RRMS pateints (Paul, 2008; Togha, 2010). MS patients in the ACTIVE trial (Atorvastatin Combined To Interferon to Verify the Efficacy) who took atorvastatin (20mg) in addition to Rebif (interferon beta-1a) had significantly fewer gadolinium-enhanced lesions after 24 months of treatment versus baseline and significantly fewer relapses. The MS patients who only received Rebif experienced a slightly elevated risk for a 1-point EDSS increase after 24 months (Lanzillo, 2010).
Statins, Oligodendrocytes, and Remyelination:
Some studies suggest that drugs such as lovastatin or simvastatin may interfere with the remyelination process in patients with MS which is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation (Miron, 2009; Klopfleisch, 2008; Smolders, 2010). Primary oligodendrocytes treated with lovastatin formed membrane sheets which were devoid of the major myelin proteins including myelin basic protein (Maier, 2009). However, another group of researchers found that lovastatin accelerated the differentiation of OPCs (Paintlia, 2010, 2008).
This all leaves me wondering whether the simvastatin I take to lower my LDL cholesterol levels may be helping my MS or hindering it. That’s a question which cannot be answered at this time but I seem to be doing well. At least I am positive that the level of “bad” cholesterol has been effectively reduced by treatment and that my cardiovascular system is healthy.
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