October 29, 2009
Simvastatin Stops Parkinson's Disease In Mice

Might a widely available cholesterol-lowering drug slow or stop the progression of Parkinson's?

(CHICAGO) –Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson's disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson's disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.

If this happens in humans surely some doctors would have noticed by now? Since Simvastatin is sold by Merck as Zocor and since at least some older patients with Parkinson's also have high cholesterol I wonder how difficult it would be to measure Parkinson's progression in patients already taking Zocor. Ditto for the other statin drugs such as lovastatin (Mevacor), rosuvastatin (Crestor), atorvastatin (Lipitor), and other statins.

"Statins are one of the most widely used cholesterol-lowering drugs throughout the world," said study author Kalipada Pahan, PhD, professor of neurological sciences at Rush University Medical Center. "This may be a safer approach to halt the disease progression in Parkinson's patients."

Pahan and colleagues from Rush, along with researchers at the University of Nebraska Medical Center in Omaha published these findings in the October 28 issue of the Journal of Neurosciences.

The authors have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson's pathology. Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson's.

25 million people world-wide use statins including 13 million in the United States (yes, the US uses more statins than the rest of the world combined). So if statins are providing a benefit against Parkinson's does this show up in Parkinson's incidence data?

I would be reluctant to take statins just to cut my risk of Parkinson's. Though for someone with a lot of genetic risk factors for Parkinson's running the other risks from statin side effects (e.g. a skeletal myopathy that damages muscles) might be worth it. My guess is that as genetic risk factors for statin side effects become known it should be possible to accurately predict your individual costs and benefits from statin usage.

Update: In the comments Dave Gore points to a 2007 study that found the protective effect is specific to simvastatin. Thanks Dave.

The researchers examined data from the Decision Support System database of the United States Veterans Affairs Medical System, a database of medical centers throughout the United States which contains diagnostic, pharmaceutical and demographic information on approximately 4.5 millions people.

Using three different models for analysis, the researchers examined the effects of three different statins (atorvastatin, lovastatin and simvastatin) and found that simvastatin showed a strong reduction in the incidence of Alzheimer’s disease in each of the models. The data also showed the same statin was associated with a reduced incidence of Parkinson’s disease.

The researchers speculate that the selective benefit observed with simvastatin might be due to the combination of high potency and the ability to enter the brain.

“The strength of reduction of incidence of dementia with simvastatin is striking,” said lead author Benjamin Wolozin, MD, PhD, a professor of pharmacology at BUSM.

Sounds promising. A good genetic test that would predict side effects might allow many people to take simvastatin for protection.

Share |      Randall Parker, 2009 October 29 10:42 PM  Aging Drugs

jmiddel said at October 30, 2009 8:34 AM:

I developed peripheral neuropathy from taking statin (Crestor), so I will not take any statin again, for whatever reason.

Dave Gore said at October 30, 2009 10:19 AM:

It isn't just any statin that has this protective effect. It is specifically simvastatin. See http://www.eurekalert.org/pub_releases/2007-07/bu-rfs071707.php .

mml said at October 30, 2009 10:24 AM:

First, there are published studies in humans looking at statins and coq10 levels. in many of these studies, evidence that statin use lowers muscle, platelet or serum coq10 is available. There were 3 other studies that were "inconclusive". CoQ10 is an essential element of the mitochondrial process that makes cellular energy--ATP. It also functions as one of the major anti-oxidants within the mitochondria, helping decrease reactive oxygen species. (important information, relating to the theory that PD is caused in part by mitochondrial dysfunction). Studies have shown parkinson's patients have depressed levels of coenzyme Q10, leading to question if depleted coQ10 is etiopathic or resultant of the disease process in Prkinson's. Use of Mega dose CoEnzyme Q10 is currently in multiple center trials for parkinson's patients to determine if the substance is neuroprotective. Shults, C., et al. authored a small study in which 1200 mgm of CoQ10 decreased progression of symptoms in parkinson's patients with early stage of the disease.
How counterintuitive is it to administer a drug for a disease which depletes a substance shown to be depleted in and possibly etiopathic ? Statins also interrupt production of dolichols, which interestingly are the primary lipid component of the substantia nigra neuromelanin (substantia nigra thought to be primary area of damage in PD. does it matter that statins interrupt the production of a major component of the neuromelanin within this structure? WHo knows? no one has asked the question)
As per prior studies looking at statins and Parkinson's, Dr. A. Lieberman authored a small study


looking at progression rates of 2 different groups of PD patients--one taking a statin, the other not on statins. His conclusion after following these 2 groups after a period of (i think ~2yrs) was that their rates of progression were "similar". Included in this study was a small paragraph noting that of the original group who were not taking a statin, 5 patients were started on a statin during the trial period. Not noted in the abstract, though noted in the full text of the study was the fact that ALL FIVE PATIENTS EXPERIENCED AN INCREASE IN SEVERITY OF THEIR SYMPTOMS AFTER STARTING A STATIN. I know that is a small #, but that's 100% of all the patients who were started on a statin during the trial period. the statin was stopped for a "washing out" period and when the symptoms did not revert, the drug was re-started. Does not increasing severity of symptoms qualify as "progression of disease?
In addition, simvastatin is a fat soluble statin, thus readily crosses the blood brain barrier. Cholesterol is a major component within the brain matter. Brain cholesterol is made de novo, and reported to have a half life of 5 to 6 yrs. The mavelonate pathway blocked by statins in the liver to decrease serum cholesterol is the same pathway utilized in the brain for production of brain cholesterol. Thus fat soluble statins would be predicted to deplete brain cholesterol levels. Given most clinical trials do not last more than 5 yrs, the results of depleting brain cholesterol may not be evident within this time frame. Does this matter?
There has been Recent discovery of a SNP in the gene encoding the transport protein responsible for movement of statins into the liver for detoxification, SLCO1B1. Possession of this SNP has been shown to result in plasma statin levels from 144% to 224% ABOVE normal, since "normal" metabolism of the statin cannot occur if it cannot get into the liver for processing. There are 2 neighboring SNPs discovered, responsible for this transport protein. One of the mutations is predicted to occur in 32% of the caucasian population; the other SNP is predicted to occur in 5% to 6% of the caucasian population.
Would like to see a study showing none of the above is relevant in PD and statin use.

medeak said at October 30, 2009 2:43 PM:

Thank you MML This release smells of a pharmaceutical funded "study"

Clarium said at October 30, 2009 6:30 PM:

I do not buy the 13 million figure for the US. I think it is larger than 4% of the US population

mml said at October 30, 2009 7:14 PM:

study was funded by NIH and MJFox Foundation, a very credible foundation. I think the information concerning SNPs in genes encoding transport proteins responsible for movement of statins into the liver to be detoxified is a very important piece of the puzzle in reference to adverse effects of statins. an increase in statin plasma levels up to 244% above "normal statin plasma levels" is huge. Again, these SNPs are prediceted to occur in 36 to 38% of the caucasian population; a large number if truly 13 million people take statins(have no idea if this # is correct nor what % is caucasian) .

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