Monthly Archives: July 2013

Could medications for high cholesterol protect against Parkinson disease (PD)?

Identifying patterns that are associated with Parkinson’s across large groups of patients—the study of epidemiology—can be confounded by many things. Health care systems in other countries like the single-payer, compulsory National Health Insurance program (NHI) implemented in Taiwan in 1995, provide a level of uniform data than is difficult to achieve in our country. A recent publication from Taiwan takes advantage of their NHI, in which over 98% of the population is enrolled, in order to shed light on the basic mechanisms of PD, and in turn on potential treatment. Parkinson’s and other neurodegenerative diseases have been thought to involve a cascade of inflammation in the brain so that inhibiting the inflammatory response may be a viable approach to therapy. Since the statin drugs that are used to treat elevated cholesterol have anti-inflammatory effects, and they have been shown to reduce alpha-synuclein aggregation in animal models, a Taiwanese team studied whether various statins could affect the risk for developing PD—i.e. could the statins be protective? Other such studies to date, using self-reporting and without the numbers of patients needed to separate out (control for) the effect of most factors that could skew the results, have been inconsistent. Lee, et al (Neurology, July 30, 2013) were able to collect information on the effect of discontinuing different statins while controlling for the accuracy of diagnosis and the co-occurrence of other diseases and drugs. They compared one class of lipophilic (fat-loving) statins to the class of hydrophilic (water-loving) statins. A significant protective effect was demonstrated only by the continued use of the lipophilic statins. Because these cross the blood-brain barrier more readily, and because the disease process starts long before symptoms appear, the authors postulate that a protective effect of lipophilic statins may exist at the level of the dopamine brain receptors rather than on the degeneration of dopamine neurons.

  • Should you switch to a llipophilic statin?
  • Should you self-administer statin-like drugs?
  • Would I be better off if I also had high cholesterol requiring that I take statins?

Of Course Not!

What we can take from this comprehensive study is the knowledge that competent researchers are chipping away at the mechanism by which cells die, and each piece that is added to the puzzle exposes a different view of the overall picture which will one day be revealed to us. KTF

Parkinson disease and Mad Cows

Irish Cows

Irish Cows

MAD COW DISEASE! The very name conjures a sort of “pastoral interruptus” in which cows lazily grazing on a grassy knoll are overtaken by a seizure-like episode, one by one succumbing and tipping over, their legs stiffly extended skyward. Dire warnings follow, lest the Bovine Spongiform Encephalitis get into the human food chain and cause a variant of Creutzfeldt-Jakob disease (vCJD).

In the early 1980’s Dr. Prusiner of UCSF described a unique disease mechanism whereby a normal brain protein misfolds, and the protein itself serves as an infectious agent in the absence of known pathogens like bacteria and viruses. He coined it the “prion” protein, derived from the words “proteinacious” and “infectious.” These infective prions literally cascade from cell to cell within the brain, acting as a template to guide the misfolding of additional proteins, which clump and hijack the normal functioning of cells leaving characteristic sponge-like holes in its wake.

Just as with Parkinson and Alzheimer diseases, some of the group of prion diseases are caused by a specific genetic change in the offending protein. Shortly after Dr. Prusiner’s won the 1997 Nobel Prize in Physiology or Medicine for his ground-breaking work, I saw a family in which several members had one of the known genetic variants of the disease. I remember feeling something akin to revulsion as I pondered what it must feel like to know something is spreading inside you, something that is impervious to an army of anti-infectious soldiers as well as to sterilization—a phenomenon not unlike the spread of cancer, I thought.

Recently, a similar self-propagating mechanism has been described for Parkinson disease in which misfolded alpha-synuclein spreads from cell to cell inducing a characteristic protein clumping. Coined “permissive templating,” it helps explain the less than stellar results from the 1990’s when cell transplants were used to replace the dopamine-deficient cells in Parkinson disease—the transplanted tissue ultimately became “infected” which defeated the purpose of the intricate procedure.

Well, now, that’s a bummer! Diagnosed with a Mad-Cow-like disease of my own and awaiting my turn at keeling skyward, the cascade occurring inside my brain, is more than disturbing!

But wait—one can always make a loaf of banana bread from a bunch of rotting bananas! A recent publication reports taking advantage of the new-found, prion-like status of Parkinson’s with a view toward treatment of both diseases. A German research group has used high-throughput screening and found a compound which prohibits formation of the pathological forms of both prion protein and alpha-synuclein {Wagner J, Ryazanov S, et al, Acta Neuropathol (2013) 125:795-813}.

Will this likely be the “magic bullet?” Perhaps not, but it opens yet one more approach to the repertoire of treatment advances which has resulted from our description of that first Parkinson disease-causing mutation in alpha-synuclein.