[Conductor71]

A while ago, Fiona started a great thread asking for proof that our neurons actually die in PD. I'm reviving it with a twist for some of our newer members based on some very current research. Here is the original thread:

http://neurotalk.psychcentral.com/sh...of+neurons+die

One of the questions asked was on apoptosis. It is what is described as programmed cell death and normally it is healthy for us. A few sources on the Internet say it is common for us to both lose and regenerate 50-70 billion cells a day. Essentially in PD, our cells in the SN are triggered by something (toxin, virus, stress and genetics) to commit mass suicide or are they being murdered? Is this essentially apoptosis run amok as in an auto-immune response, or is it an assault by something that fatally disarms our cells? BTW, here is a really great primer on apoptosis.

There is proof that most of our dopaminergic cells in this area of the brain do die off, but curiously they don't all die. I'd say although crude, PET scans and more accurately, post mortems show that they die. However, we don't end up losing all of them. Recent research published just this month is the first to measure through PET scan the brains of people with long-standing PD (duration at least 20 years). Surprisingly, they found a "reserve" of dopaminergic cells showing that there is a reason not all die off and giving hope that neurorestoration is somehow possible.

Residual striatal dopaminergic nerve terminals in very long-standing Parkinson's disease: A single photon emission computed tomography imaging study.

Doesn't it stand to reason that by looking at the remaining cells that they would yield clues as to how they end up surviving in comparison to the tangled Lewy bodies left behind by the ones that drank the kool-aid. Or, is there something in us that regulates that we will retain 10-15 % (arbitrary number) of our neurons? If we could just harness the power of what that something is....
Even if we could just start measuring how much neuronal loss we have at diagnosis as a baseline, we could at least scientifically chart clinical progression for a change. This would give us much more of a sound base for staging the disease then the Hahn & Yoehr. All these what ifs. You'd think I'd learn by now.

Finally, here is a really informative article on just what is going on at the cellular level in our brains (and in AD and Huntington's). Turns out that it looks like a valiant attempt is made to save our cells but those nasty unfolding proteins get in the way and they end up dying instead.

Cellular Stress Responses: Cell Survival and Cell Death

Why isn't science focusing on more treatments to interrupt this process? To date, I think the Alpha-Synuclein targeted vaccine being developed and tested next year at Affiris is the only treatment in the pipeline that even comes close. Can we participate in clinical trials worldwide? The vaccine trial starts next year but in Austria.

Laura

[lurkingforacure]

[Why isn't science focusing on more treatments to interrupt this process? To date, I think the Alpha-Synuclein targeted vaccine being developed and tested next year at Affiris is the only treatment in the pipeline that even comes close. Can we participate in clinical trials worldwide? The vaccine trial starts next year but in Austria.]

Laura,

The University of Nebraska is also working on a PD vaccine, Prof. Gendelman is heading that up. They are at the stage of testing folk (selection already done, apparently) to compare the immune system of people and the mice used in the study. I actually called him and spoke with him, he was very generous with his time and I learned a lot. I found it interesting that he was very clear to say this is not a cure in the sense that it could revive already dead neurons, nothing can do that, obviously, but that at least in the rodent model they used, it did make the sick neurons better and appeared to stop the process. Look it up and check it out if you want more.

Additionally, it seems that somewhere in Texas they are also working on a PD vaccine...it was maybe Houston or Dallas, I'm not sure which. The article indicated they were not as far along as Affiris nor Gendelman's group. Of the three, Affiris is way ahead. BUT...my understanding of Affiris' and Gendelman's vaccine is they are not the same! If I remember correctly, they have different mechanisms of action (one attacks the plaques, one keeps them from forming, something like that). Sorry, layman's understanding, and I read about this stuff six months ago and can't remember it exactly. Just wanted you to know that more folks are working on a PD vaccine than Affiris, and right here at home.

[VICTORIALOU]

In a recent (sept. 28, 2010) Science Daily article......

"The team found that lack of Rab1a impaired autophagosome formation, whereas an abundance of the GTPase reversed the inhibitory effects of alpha-synuclein on autophagy. "

is Rab1a one of the substances being developed?

the article is referring to the Sept 20th issue of the Journal of Cell Biology

Victoria

Originally Posted by lurkingforacure

[Why isn't science focusing on more treatments to interrupt this process? To date, I think the Alpha-Synuclein targeted vaccine being developed and tested next year at Affiris is the only treatment in the pipeline that even comes close. Can we participate in clinical trials worldwide? The vaccine trial starts next year but in Austria.]

Laura,

The University of Nebraska is also working on a PD vaccine, Prof. Gendelman is heading that up. They are at the stage of testing folk (selection already done, apparently) to compare the immune system of people and the mice used in the study. I actually called him and spoke with him, he was very generous with his time and I learned a lot. I found it interesting that he was very clear to say this is not a cure in the sense that it could revive already dead neurons, nothing can do that, obviously, but that at least in the rodent model they used, it did make the sick neurons better and appeared to stop the process. Look it up and check it out if you want more.

Additionally, it seems that somewhere in Texas they are also working on a PD vaccine...it was maybe Houston or Dallas, I'm not sure which. The article indicated they were not as far along as Affiris nor Gendelman's group. Of the three, Affiris is way ahead. BUT...my understanding of Affiris' and Gendelman's vaccine is they are not the same! If I remember correctly, they have different mechanisms of action (one attacks the plaques, one keeps them from forming, something like that). Sorry, layman's understanding, and I read about this stuff six months ago and can't remember it exactly. Just wanted you to know that more folks are working on a PD vaccine than Affiris, and right here at home.

[pegleg]

Why scientists aren't putting more effort into the adaptability (plasticity) of neurons, I will never know. In the '60's, researchers discovered in animal models (later confirmed in human imaging studies) that when brain cells die (apoptosis) they are not gone forever. That was a HUGE discovery! If we could only "tag" those newer cells created, then we might be able to determine why some survive, some die, and new ones are created and/or old ones are restored or changed.

I have long believed that the answers as to why we get neurological diseases lie within the single cell (mitochondria). In high school we called this the little "power house" of each cell. Its where the energy is created and where cell changes begin (in theory). Gene therapy comes closest to the science based on this theory. But I feel we don't know enough about changing genes in a person to be injecting a virus in there to clean up - mutate - or alter these power houses.

I am of the opinion that we need to change the chemical composition of our brain's neurotransmission BEFORE we start reconstructing how our brains produce, kill, or alter neurons. The older GDNF studies are good examples. We hypothesized that Neurons bathed in growth factors like GDNF, Neuturin, etc. improved their plasticity (or maybe they simply improved the neurotransmitting pathways). And we saw visible results in such trials in a rather short time. (and no way can placebo effect be the reason for such observable improvements). An autopsy of a GDNF trial participant (cause of death unrelated to PD) showed neural sprouting, what should have been the biggest revelation in the history of neuroscience. Yet, it was merely mentioned in the news then stored away in some journal.

We need to study lots and lots of similar data based on this theory more. Gene therapy in the past has had disastrous human results. What made researchers think that they know enough about it now to shoot these cell-altering viruses into human brains??

23andme was (and still is) a fantastic way to review such information by doing a genomic analysis of individuals DNA (remember the "Spit Kits?") The company is still offering such analyses of individuals already afflicted with Parkinson's - a sizeable discount for such information ($25 if you have PD in lieu of the usual $300). Go to the Fox Foundation website -or any of the Parkinson's orgs and do a search for "23andme" - no spaces between words. And the survey follow-ups are VERY important is this data collection is to be beneficial (and I am behind in doing my homework)!

Sorry to rattle on - not intended.. . but this is dear to my heart (and brain).
Peggy