"A new study led by researchers at Columbia University Medical Center has identified a novel molecular pathway underlying Parkinson's disease and points to existing drugs which may be able to slow progression of the disease.

The pathway involved proteins – known as polyamines – that were found to be responsible for the increase in build-up of other toxic proteins in neurons, which causes the neurons to malfunction and, eventually, die. Though high levels of polyamines have been found previously in patients with Parkinson's, the new study – which appeared in an early online edition of Proceedings of the National Academy of Sciences – is the first to identify a mechanism for why polyamines are elevated in the first place and how polyamines mediate the disease.

The researchers also demonstrated in a mouse model of Parkinson's disease that polyamine-lowering drugs had a protective effect.

"The most exciting thing about the finding is that it opens up the possibility of using a whole class of drugs that is already available," says Scott A. Small, MD, the senior author of the study and Herbert Irving Associate Professor of Neurology in the Sergievsky Center and in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center. "Additionally, since polyamines can be found in blood and spinal fluid, this may lead to a test that could be used for early detection of Parkinson's."

http://www.eurekalert.org/pub_releas...-npi091310.php

http://www.jbc.org/content/278/5/3235.full

PLEASE NOTE THE DATE OF THIS ABSTRACT
Imad
The relevance of glial monoamine oxidase-B and polyamines to the action of selegiline in parkinson's disease
Prof. M. B. H. Youdim, P. RiedererArticle first published online: 12 OCT 2004/ OI: 10.1002/mds.870080504

Abstract
Dopamine and 2-phenylethylamine levels in striatal tissue are known to be increased after administration of selegiline (L-deprenyl), but it is still difficult to explain why this treatment induces longevity or dopaminergic neuroprotection in Parkinson's disease. In the absence of significant polyamine or diamine oxidase activities in human brain, polyamines and histamine are detoxified by N-acetylation and methylation, respectively. Methylhistamine as well as N-acetylated polyamine derivatives are selective substrates for monoamine oxidase type B (MAO-B). Theoretically at least, MAO-B inhibition by selegiline could result in the increase in the levels of polyamines and their N-acetyl derivatives. This could have significance for the action of selegiline in Parkinson's disease, as overactive corticostriatal glutaminergic function has been implicated in the degeneration of nigrostriatal dopamine neurons, and polyamines are potent modulators of the excitotoxic NMDA (N-methyl-D-aspartate)-glutamate subtype receptor.

I am trying to figure this out. According to scientists, too many polyamines result in increased excitoxicity and result in us losing dopaminergic neurons.
Yet, a PD drug, Selegiline, long purported to be neuroprotective actually fosters proliferation of polyamines. In other words, it may be more harmful, than good? Or does something else happen that balances out or cancels out the harmful effect of the polyamines?

Confusing to say the least...

Laura

Laura, I thought the same thing...we've been on azilect since it became available in the US. I don't really understand this either, if polyamines are not good in excess, why a drug that fosters proliferation of them would be beneficial. Note: We have been on azilect since it became available in the US, and we have definitely progressed, I can't even say I believe it has slowed what progression we would have had if we hadn't been on it. And of course if you take azilect, you cant' take a whole bunch of other stuff which I believe is helpful, like DM, benedryl, etc. Maybe we would have progressed slower if we HADN'T been on azilect, now wouldn't that be the kicker?

Lurking,

I am beginning to realize that most good neurologists believe that many of the drugs we take are "iffy". I sometimes think this is why my MDS is recommending DBS sooner than later; not ready yet, I am hopeful that vaccine or GAD GABA therapy works before that time.

As for Azilect, I have been skeptical because the co-inventor (Youdim) relentlessly pursues any possible angle of setting this drug apart from other PD treatments. It's like they are desperately trying to come up with some unique quality that might exist. Rasagiline has neuroprotective activity; it is an antidepressant; it's leading to a new treatment for Alzheimer's; it induces GDNF neurotrophic factor; it is an iron chelator...I mean really, it does all that? A search on pubmed leaves you reeling. I would think it is primarily great at one thing, and they haven't quite discovered what that is yet other than it is better than Selegiline because it doesn't break down into an amphetamine. Sorry about that rant, but I get so peeved at all the different slants on this drug and it all centers on profit.

Not to worry...we are all doomed. I just read an article that points out our gold standard Sinemet leaves behind toxic goodies in the form of O-methyldopa that in turn increases homocysteine levels. This can cause serious vascular problems involving arteries and may also put out the welcome mat to dementia! To counteract this it is recommended we increase our folic acid or take Entacapone (a COM inhibitor which many here do take), but that in turn increases N-methyldopa which can produce a toxic compound that results in...PD symptoms!

I read this and thought now scientists are just screwing with us, but no it's our reality. Gives new meaning to the adage "It can cure you, if it doesn't kill you first."
Role of homocysteine in the treatment of Parkinson's

On plus side...take a look at green tea and rasagiline thread here at NT

Laura

There is a drug that has been and is still being tested as a cancer preventive which inhibits the first enzyme in the synthetic pathway of polyamine synthesis. It is alpha-difluoromethyl ornithine, DMFO. It would seem to be a prime candidate for neuroprotection if excessive polyamines are involved in PD pathogenesis.
Robert

Well, I guess it is good to know that, on the other hand, ignorance can be bliss! Perhaps that is why our neuro recommended we take 800mg of folic acid a day, which we do...hopefully the homocysteine levels are low but we haven't had a blood test in awhile...

I wonder if these byproducts are why some believe long term levodopa is toxic, although that theory has been poo-pooed by the Mayo doc who wrote "Beating a Dead Horse" which is all about why PD is not just about levodopa. And it certainly explains why symptoms can get worse, it's hard to tell if you are progressing because you are progressing or because your meds are giving you some nice side effects. It's impossible to know.