Statin activity in treating MS

Post by **NHE** » Wed Apr 06, 2005 2:06 am

This paper from the journal Nature may be old news (it's from 2002). However, I just ran across it and I thought that I would post the abstract here since it discusses some of the actions of statins that explain their efficacy in treating MS.

The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease.

Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, Zamvil SS.

Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, California 94305, USA.

Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are approved for cholesterol reduction, may also be beneficial in the treatment of inflammatory diseases. Atorvastatin (Lipitor) was tested in chronic and relapsing experimental autoimmune encephalomyelitis, a CD4(+) Th1-mediated central nervous system (CNS) demyelinating disease model of multiple sclerosis. Here we show that oral atorvastatin prevented or reversed chronic and relapsing paralysis. Atorvastatin induced STAT6 phosphorylation and secretion of Th2 cytokines (interleukin (IL)-4, IL-5 and IL-10) and transforming growth factor (TGF)-beta. Conversely, STAT4 phosphorylation was inhibited and secretion of Th1 cytokines (IL-2, IL-12, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha) was suppressed. Atorvastatin promoted differentiation of Th0 cells into Th2 cells. In adoptive transfer, these Th2 cells protected recipient mice from EAE induction. Atorvastatin reduced CNS infiltration and major histocompatibility complex (MHC) class II expression. Treatment of microglia inhibited IFN-gamma-inducible transcription at multiple MHC class II transactivator (CIITA) promoters and suppressed class II upregulation. Atorvastatin suppressed IFN-gamma-inducible expression of CD40, CD80 and CD86 co-stimulatory molecules. l-Mevalonate, the product of HMG-CoA reductase, reversed atorvastatin's effects on antigen-presenting cells (APC) and T cells. Atorvastatin treatment of either APC or T cells suppressed antigen-specific T-cell activation. Thus, atorvastatin has pleiotropic immunomodulatory effects involving both APC and T-cell compartments. Statins may be beneficial for multiple sclerosis and other Th1-mediated autoimmune diseases.

NHE

carolew · Post by **carolew** » Sat Apr 08, 2006 7:46 am

This is the exact article that got me to take Lipitor! I am still waiting for the results of more formal studies. I beleive they are taking place right now.
Carole

dignan · Post by **dignan** » Fri Apr 21, 2006 8:03 am

Here is another paper that talks about statins and MS, among other diseases. Not sure if it adds anything new, but thought I'd throw it out there...

Summary
For reasons that go beyond cholesterol reduction, the most widely used prescription drugs in the US are being explored as treatments for central nervous system disorders, including multiple sclerosis (MS) and Alzheimer’s disease. Statins exhibit a variety of immunomodulatory effects in MS, and so far, pilot trials have found them to be safe. In Alzheimer’s disease, epidemiologic findings linking statins to reduced risk of dementia remain controversial.

http://www.neura.net/images/pdf/Winter06Statins.pdf

bromley · Post by **bromley** » Fri Apr 21, 2006 8:33 am

Thanks Dignan.

When I met my neuro a few weeks ago I mentioned statins and he responded "they cause muscle damage". The UK MS Society is holding a conference this weekend and one of the presentations is about statins. I'll post the results but I suspect it will be "on the one hand... on the other hand...".

What is so frustrating is that therapies are identified which might help, such as statins, monocyline etc, then years go by and trials are in progress, but no-one ever comes up with a definitive answer - are they worth taking or not? This disease must be a researchers dream.

Ian

Loriyas · Post by **Loriyas** » Fri Apr 21, 2006 8:56 am

My neurologist wanted me to try Lipitor along with my Copaxone, so I agreed. I have been taking the Lipitor for only about 3 weeks with no side effects as yet. I will be getting blood tests done next week to check liver among other things. I then have a follow up with the neurologist to see results. I'll let you know how it goes then.
Lori

bromley · Post by **bromley** » Fri Apr 21, 2006 10:09 am

Lori,

I'd be interested in hearing how you get on with the Lipitor.

I see that you're from Naples, Florida. We've been holidaying there for the last six years and love the beaches. At least you've got no excuses for not getting enough Vit D from the all year sunshine.

Ian

Loriyas · Post by **Loriyas** » Fri Apr 21, 2006 10:28 am

Ian
I truly believe in the benefit of Vit D and sunshine! In fact, we used to live in Columbus, OH. We vacationed here in Naples often. After I was dxd I found that I felt better here. So we decided to make it permanant and moved here. I am sure that the sunshine helps tremendously (even if it is just in my mind!) It doesnt' really matter, does it, as long as it works?! Let me know if you vacation here again.
Lori

Brainteaser · Post by **Brainteaser** » Tue Apr 25, 2006 12:08 am

Hi Bromley,

Any feedback from the UK MS Conference regarding the use of statins?

It would seem encouraging that this treatment is being discussed at such a conference and also that particular neuros are now prescribing statins, albeit in conjunction with the interferons/copaxone.

Thanks & regards,
Phil.

bromley · Post by **bromley** » Tue Apr 25, 2006 9:05 am

Phil,

I didn't attend the event but expect the UK MS Society to put a summary of the different presentations on its website in due course. I will monitor and post here.

Ian