Neurodegener Dis. 2010 Feb 27. [Epub ahead of print]
Low Dosage of Rasagiline and Epigallocatechin Gallate Synergistically Restored the Nigrostriatal Axis in MPTP-Induced Parkinsonism.

Reznichenko L, Kalfon L, Amit T, Youdim MB, Mandel SA.

Eve Topf Center for Neurodegenerative Diseases Research and Department of Molecular Pharmacology, Faculty of Medicine, Technion, Haifa, Israel.
Abstract

Background: The anti-Parkinson monoamine oxidase B inhibitor rasagiline appears to be the first neuroprotective disease-modifying therapy in early-stage Parkinson's disease (PD). Objective: Using a polypharmacy paradigm, we tested whether the distinct neuroprotective pharmacological profile of rasagiline would complement that of (-)-epigallocatechin-3-gallate (EGCG), the main antioxidant/iron chelator polyphenol constituent of green tea, and restore the neuronal loss and molecular targets damaged in animal parkinsonism. Methods/Results: We show by high-performance liquid chromatography, immunohistochemistry and Western blot analyses that the combination of rasagiline and EGCG, at subliminal doses which have no profound protective effect, acts synergistically to restore the nigrostriatal axis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. A detailed analysis revealed a complementary action of these drugs, differentially acting at MPTP-injured molecules/targets in the substantia nigra (SN): induction of brain-derived neurotrophic factor by rasagiline, increased membranal levels of the protein kinase C alpha-isoform by EGCG and a synergistic replenishment of their downstream effector, the serine/threonine kinase Akt/protein kinase B, suggesting that this kinase might represent one point of convergence of the distinct mechanisms of action of the drug cocktail. Conclusion: These results provide molecular evidence that activation of multiple brain targets by the combination of rasagiline and EGCG may synergistically contribute to the rescue of the dopamine neurons in the SN and replenishment of striatal dopamine. This may have important implications for rasagiline-treated PD patients who could further benefit from an adjunct administration of EGCG.

PMID: 20197647 [PubMed - as supplied by publisher]

Hmmm...why isn't TEVA jumping all over this? It seems to me that they could even reformulate Azilect with ECGC and market it as truly neuroproctive. This study sounds way more conclusive than the recent ADAGIO delayed start research that showed conflicting results. In fact, this study rather supports the ADAGIO finding that Azilect was neuroprotective at 1 mg only (no benefit for people at 2 mg).

I have a stash of Azilect samples in my hall closet. I had to stop taking it due to joint pain side effect; the White Rat in me is oh so tempted to now experiment with this.

Also wonder how this low, below therapeutic dose finding relates to the DX and Naltrexone approach to neuroprotection?

Laura

Laura-
There is something about low dose approaches that I haven't quite gotten my mind around. There is this one and the LDN. Then there is dextromethorphan which has one effect at a very low dose and an entirely different one at a slightly higher dose.

It is almost as if there is a low dose effect that is quickly overwhelmed as it increases. Mucuna is another. Curcumin as well.

A clue may be found in the action of toxins. Repeated exposure to tiny amounts of environmental poisons can be far more deadly than a single, but much larger, one. The latter permits your detox systems to deal with it and repair to begin. The former just wears you down. Maybe a little bit of some of these triggers repair.

Is there full funding disclosure available for this one?

The team kindly furnished me a PDF <email me at address below> and it does, indeed, seem to be important. The emphasis is not on rasagaline nor is it entirely on EGCG (tea). It is also about treating a complex disorder like PD with a complex, multifunction remedy that allows for synergy. Also, there is no obvious funding conflict.

Add to Laura's experience; my neuro Dxd .5 mg Azilect supplementing 300mg Stalevo---side effects---joint pain,freezing, low BP. I suggest leaving the tests with the mice!!

Well, Lordy! That darn Stalevo will kill you! Three drugs together, it's a wonder you're alive!

Joint pain? Freezing? Low BP? You call those side effects? Why, in my day a "side effect"....<mutter...mutter>

When I was diagnosed I found an article about neuroprotection by green tea. One of the authors is co-inventor of rasagiline (Moussa Youdim) so I considered the information relevant. I asked my neurologist and he said there's no problem in taking it, so I've been taking Azilect and green tea capsules for the last 10 months.

I know it's too early, but I haven't noticed any worsening in my condition, so I'll keep betting on this combination: rasagiline, EGCG and exercise.

For those interested the article is available here. There's even an indication of the dosis: 2mg/Kg. Above that neuroprotection could turn into neurotoxicity.

Doesn't it work with coffee Rick? I guess not. I think I'm gonna try this one.
The Adagio study challenged me to switch to 0.5 mg azilect per day. The side effects I had were pain in the neck area and a strange feeling in my head. It is much better now with half the dose I used to take. I might add the green tea to the menu and see if I notice something. It's a pity I dont like tea very much.

I read that it is only green tea that has the high levels of catechins in it, and dosage is critical, as other have noted...a little helps, a lot makes things worse.

Here is a video of Dr. Mandel of the Technion Institute discussing green tea, she puts it pretty clearly (and SO much easier to understand than the article JoeM shared with us, whew-ee, that pretty much blew what little brain I have left! Incredibly informative though, I loved the detailed discussed of the authors' theory about neurodegeneration and the processes involved in same (including disruption of the BBB, Ron!)....we'll be sharing it with our doc next time we see him.). here' the video link:

http://www.ats.org/site/PageServer?p...out_parkinsons


I also think it is very interesting that the article listed by JoeM basically shows that PD is a process, which is why one pill is NOT going to fix things...there are many events all of which seem to work towards cell death, and my thinking is if we can address enough of the obstacles along the highway, maybe green tea for inflammation and chelation of the excess iron in the brain, coQ10 for helping the mitochondria, etc., eventually it will clear up. One thing Dr. Mandel said on the video that really perked up my ears was that the catechins in green tea can:

1. cross the BBB
2. enter the cells/neurons in the brain and
3. once there, they not only chelate out the excess iron and I believe copper as well, but also increase the expressions of the genes in the cells that code for survival. I got from her that green tea is actually neuro-restorative, let me know if I got that wrong.

So how many cups of green tea does one drink a day? Also, this is important, I also read that you will radically increase the absorption of the catechins in the green tea if you add a bit of citrus to it...think everyone here already knows this but I had forgotten.