I fought my doctor when she prescribed statins to lower my dangerously high cholesterol. Instead, I lost 10 pounds (actually 10.4 pounds but who’s counting), ate a more healthy diet and bumped up my exercise regime. My cholesterol level didn’t budge until I began simvastatin (Zocor) in mid-August of 2009.
As it turns out, statins may be protecting my heart as well as my Parkinson’s progression as indicated in the following article from MedPage Today:
Statins Protect Against Parkinson's Progression in Mice
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: November 02, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Statins may slow the progression of Parkinson's disease by preventing the cascade of inflammatory damage to neurons that eventually leads to motor dysfunction, according to a mouse model study.
Mice given the equivalent of standard simvastatin (Zocor) or pravastatin (Pravachol) doses lost fewer dopaminergic neurons and neurotransmitters, Kalipada Pahan, PhD, of Rush University Medical Center in Chicago, and colleagues found.
The mice also had significant improvements in all measures of motor function, they wrote in the Oct. 28 issue of the Journal of Neuroscience.
Although safety would likely not be a concern for translating these results into the clinic, Pahan cautioned against prescribing statins without a cardiovascular indication in Parkinson's disease until there are clinical data to support it.
His group plans a Phase II trial in Parkinson's patients.
Observational data from case-control and large cohort studies have suggested that taking a statin nearly halves the risk of incident Parkinson's disease.
"But that did not suggest whether statins could actually reverse the existing disease," Pahan noted.
So his group tested this hypothesis in mice given injections of a neurotoxin that induces parkinsonism.
First, though, they ran a few tests in the microglial cells that are known to play an important role in the pathogenesis of Parkinson's and other neurodegenerative disorders.
They found that one step in microglial activation was the activation of a proinflammatory protein, p21ras, which appeared to be necessary for the neurotoxic chemical to produce Parkinson's.
But simvastatin exposure inhibited the activation of p21ras (P=0.0006 to P=0.0002) in the microglial cells. The statin also blocked the neurotoxin from activating (P<0.0001) nuclear factor-kappaB, "a transcription factor required for the transcription of most of the proinflammatory molecules."
Mice given the parkinsonism-inducing neurotoxin showed the same P21ras activation in the cells of the ventral midbrain, while those given only saline injections showed little or no activation.
Even when given simvastatin or pravastatin after the neurodegenerative process had started, mice with simulated Parkinson's had significant reductions in midbrain expression of proinflammatory molecules, including inductible nitric oxide synthase (P<0.0001), p21ras, and nuclear factor-kappaB.
Both statins also suppressed activation of glial cells in the ventral midbrain, although pravastatin appeared to be somewhat less effective.
Whereas the neurotoxin dramatically reduced the number and concentration of dopaminergic neurons and density of dopaminergic fibers compared with controls, both simvastatin and pravastatin significantly prevented these types of degeneration (all P<0.001).
Again, simvastatin appeared to hold an advantage over pravastatin.
Striatal dopamine levels were reduced 78% in the Parkinson's model mice compared with controls, but statin treatment lowered the loss to only 21% to 26%.
Not only were neurons and neurotransmitters protected, but motor function was preserved as well.
Mice given the statins moved around more often, faster, and with less resting (all measures P<0.05 to P<0.001) than the nonstatin mice.
Even when statins weren't started until two days after mice were given the neurotoxin and the disease process began, the drugs still inhibited the demise of dopaminergic neurons and loss of neurotransmitters, "suggesting that statins are capable of slowing down the progression of neuronal loss in the [Parkinson's disease] mouse model," the researchers wrote.
Currently the most effective option for treating Parkinson's disease clinically -- levodopa plus carbidopa (Parcopa or Sinemet) -- helps only 30% to 40% of patients, Pashan noted.
If clinical studies of statins pan out for Parkinson's disease, "it would be a big advancement," he said. "We don't need to use a higher dose."
Doses many times higher than the 80 mg doses typically used for cholesterol lowering have actually been shown to be neurotoxic, he cautioned.
The reason for the difference between the statins might have been that simvastatin penetrates the blood-brain barrier better, whereas pravastatin only did so after parkinsonian neurodamage started in the mice, the researchers suggested.
The study was supported by National Institutes of Health grants and the Michael J. Fox Foundation for Parkinson's Research. The researchers provided no information on conflicts of interest.
Primary source: Journal of Neuroscience
Source reference:
Ghosh A, et al "Simvastatin inhibits the activation of p21ras and prevents the loss of dopaminergic neurons in a mouse model of Parkinson's disease" J Neurosci 2009; 29: 13543–56.
Action Points
· Caution interested patients that statins have not been clinically tested or FDA approved for prevention of Parkinson's disease onset or progression.
· Caution patients that these results were reported in mice who were given a neurotoxin to stimulate parkinsonism, and the treatment may not have the same effect on humans with the disease.
Everytime I see an article about statins, I automatically see the word, SATIN, instead, and wonder how satin can help with Parkinson's. Might be easier to turn over in bed with satin sheets and satin pajamas?
thanks for posting this!
Posted by: Terri Reinhart | November 19, 2009 at 08:17 AM