A bunch of things


#1
This is an interesting article explaining that a combination of 3 elements is causing parkinson's disease and that if only 1 could be eliminated, PD could be stopped:

http://www.sciencedaily.com/releases/2009/04/090429132222.htm

However, the article also claims that dopamine release triggers alpa-synuclein to clump. So I was thinking ... are the PD meds fastening up death of DA neurons ? So I found this:

http://neurotalk.psychcentral.com/showthread.php?t=145293

Apparently L-dopa stimulates neurodegeneration of DA neurons. This is frightening. The dopamine is converted into DOPAL by MAO. And DOPAL is toxic for the DA neurons. In a normal brain DOPAL gets cleared up, but people with PD have a failure in the cleanup mechanism and therefore 4.4 times more DOPAL in their brain (post-mortem analysis). At the same time, this explains why azilect might be neuroprotective. As azilect inhibits MAO more dopamine is present in the brain, but less gets converted into DOPAL. So I think that due to azilect less DOPAL is in the brain than in a normal brain so less needs to get cleared, which is perfect for people with PD as their clearing system is malfunctioning.

Taking this into account I think the GM1 ganglioside study is of crucial importance. Even if symptomatic improvement is the result of GM1 rewiring the brain, than still its benefit is unbelievably huge for PD patients. So I think that Dr. Schneider should heavily push for GM1 ganglioside.

After a little bit of more investigation I also found that there are neuroprotectants that in vitro have shown that they protect against L-dopa induced toxicity:

http://europepmc.org/abstract/MED/22196758 (baicalein)

http://www.hygeiajournal.com/Downloads/14462412784Amelioration%20of%20cns%20toxocities.pdf (tinospora cordifolia)

I think these findings are very important. It shocks me these things are not really considered or discussed in PD community.

#2
Azilect reduces DOPAL induced a-synuclein aggregation:

http://www.mdsabstracts.com/abstract.asp?MeetingID=787&id=99911

#3
I know I am posting a bit too much again, but the more I dig into this, the more interesting things become:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284575/

This mouse models looks more interesting to do preclinical testing with than the standard mouse models they use.

#4
Nice research MisterX. The DOPAL hypothesis is being worked on by several groups. Once again, is the decrease of the detoxifying enzymes a cause of or an effect of a dying neuron?

#5
Bartobob, I am definitely not an expert. But the hypotesis that goes around at the moment does make sense. It is known that there is a link between PD and pesticides. I read that something in the pesticides gives raise to something else that inhibits the detoxification process in the brain. As a consequence of this, more DOPAL is present. DOPAL is only toxic to dopamine neurons, so this could explain why only the dopamine neurons are initially dying in PD patients. It has also been shown that due to excessive DOPAL a-synuclein gets clumped and starts attacking neurons too. And many studies have already confirmed presence of these clumps in PD brain. Yesterday a new study confirmed this again (http://www.sciencedaily.com/releases/2013/02/130207141402.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29)

There are other things indicating this. There have been levedopa studies to show whether L-dopa slows down progression of PD. Symptomatically it looked like it slowed PD down. But brain scans showed less neurons. So scientist were confused at that time. But the study of the thread I posted confirms that L-dopa fastens neuronal death.

This theory fits every piece perfectly together.

So knowing this, the best thing to do is avoid L-dopa as much as possible. It shocks me to realize that many doctors just immediately prescribe L-dopa in recently diagnosed patients. The first doctor my father went to prescribed him L-dopa. I said the doctor was crazy and I sent him to a different one in a city 45 minutes away from ours. He gave him azilect and mirapex. After doing all this research I did, I am happy we didn't listen to the first doctor.

In fact, today I investigated mirapex and its mechanism and again it shows mirapex is much better than L-dopa. It replaces dopamine, so things work great again without creation of extra DOPAL. Even if the day comes that you need to take L-dopa, my thought is that you should always keep combining this with azilect and mirapex. Azilect at least seems to inhibit a-synuclein clump formation (see one of the links I posted here). And Mirapex is can still be working as a dopamine replacement that doesn't create DOPAL. At the same time, less L-dopa will be needed if both drugs are taken.

Oh ... I also have an aunt with PD. She is 80 years old. She is also taking L-dopa as first treatment. I will need to contact my uncle and tell him about my research here.