[imark3000]

I am always hoping that some body will get us out of the 50 years old dopamine box.
Imad

http://www.telegraph.co.uk/science/s...s-in-mice.html

Scientists have established for the first time how specific "pathways" in the brain control our movements, opening the door for pioneering therapies to improve the motor skills of sufferers.

The discovery could also be used to develop treatments and drugs to improve the day-to-day lives of people with similar disorders including Huntington's disease and Tourette's syndrome, according to academics
,,,
Earlier this month scientists announced plans to restart research into a promising treatment for Parkinson's disease after overcoming a debilitating side effect that caused human tests to be abandoned nine years ago.

In the latest study by the Gladstone Institute of Neurological Disease (GIND) and Stanford University in the US, scientists used genetic techniques to make certain "pathways" – or circuits – in the brains of mice responsive to light.

The cells in these pathways could then be turned on and off by illuminating a laser shined through a hair-thin fibre optic cable inserted into the rodents.

[pegleg]

The side effect was (and is) dyskinesias.

This breakthrough is related to this article also:
http://www.telegraph.co.uk/health/he...liminated.html

"Dr Politis said earlier trials showed the surgery could produce "remarkable improvement" in some patients but the majority suffered serious disabling adverse effects.

He said dyskinesia is a common side effect of drugs used to treat the symptoms of Parkinson's disease but the patients were suffering involuntary uncontrolled movements while off their drugs.
The new research, which is published online today in Science Translational Medicine, scanned the brains of two Parkinson's sufferers who suffered dyskinesia following surgery.

Dr Politis said researchers found the side effect was the result of an overabundance of serotonin cells in the transplanted tissue."
June, 2010

The article states that the increased seritonin is no big deal:

Researchers funded by the Medical Research Council (MRC) and Imperial College London now believe dyskinesia was caused by malfunctioning serotonin cells and say the disorder can be treated with drugs

So what drug(s) is he referring to???

[Conductor71]

Peg,

All that is as clear as mud; I can't tell if they mean a drug to control dyskinesia side effect from this so-called novel fetal stem cell procedure...or are they referring to levodopa and longstanding problems with dyskinesia.

Either way, they would be doing it over my akinetic or dead body...this is way too experimental and outside the box for me. Did you see what they are suggesting?

This could be prevented through drugs, he said, adding that the team suggested serotonin cells be removed during the preparation of transplanted tissue in future trials which they hope will now be able to take place.

I am speechless. First, they have no idea what is really going on with us in the first place; it would seem having a firm disease etiology in place and knowing without a shadow of a doubt that serotonin is the culprit in dyskinesia would be established before you even think about removing serotonin cells from one's brain because you think they are in excess! Wow.
They have no clue as to what is really going on up there, and they want to play directly with another of our neurotransmitters? This sounds really "off" to me, so maybe the reporting is not entirely accurate?

Laura

[pegleg]

Yes, this is a confusing article (or the mix of the two articles), but that's how science is.

The article I quoted (6/30/2010) is highlighting that the fetal tissue cell transplant trials from 1999, were halted due to runaway dyskinesia. That article claims to have now found a way to take care of that problem and restart that trial.

Quoting:
"We know that the benefits of this treatment could last up to 16 years, and we look forward to bringing this treatment one step closer to a reality for Parkinson's patients."
* * *
Then he (Dr, Polis) goes on to say:
He said dyskinesia is a common side effect of drugs used to treat the symptoms of Parkinson's disease but the patients were suffering involuntary uncontrolled movements while off their drugs.

The new research, which is published online today in Science Translational Medicine, scanned the brains of two Parkinson's sufferers who suffered dyskinesia following surgery.

Dr Politis said researchers found the side effect was the result of an overabundance of serotonin cells in the transplanted tissue.
This could be prevented through drugs, he said, adding that the team suggested serotonin cells be removed during the preparation of transplanted tissue in future trials which they hope will now be able to take place.
Source: http://www.telegraph.co.uk/health/he...liminated.html

I was asking what "DRUGS" he was referring to?? And can the dyskinesias we have from long-term L-dopa use be treated the same way?

The article imark3000 linked to (7/7/2010) says thisExcerpted quotes)

Earlier this month scientists announced plans to restart research into a promising treatment for Parkinson's disease after *overcoming a debilitating side effect that caused human tests to be abandoned nine years ago.

*(my words - the debilitating side effect being dyskinesia.)

In the latest study by the Gladstone Institute of Neurological Disease (GIND) and Stanford University in the US, scientists used genetic techniques to make certain "pathways" – or circuits – in the brains of mice responsive to light.

The cells in these pathways could then be turned on and off by illuminating a laser shined through a hair-thin fibre optic cable inserted into the rodents.
* * *
Dr Kreitzer said: "We generated mice that lacked dopamine, and these mice showed many of the same symptoms found in humans with Parkinson's disease. But when we activated the 'go' pathway in these mice, they began to move around normally again.

"We restored all of their motor deficits with this treatment, even though the mice still lacked dopamine."

Dr Kreitzer added: "It's not something we can do for just a second. We can do this for as long as the laser is on."

So it appears that in mice trials only (so far) that laser light stops or controls the extra movements seen in PD symptoms. Could laser treatment also possibly take care of the dyskinesia.?
Source: http://www.telegraph.co.uk/science/s...s-in-mice.html

So here's what I gathered from the two articles:
1. The fetal tissue transplant (human) trials were stopped 9 years ago due to the development of runaway dyskinesia.
2. The fetal tissue dyskinesia was caused by too much seritonin in the transplanted tissue, which can be removed if these trials start up again. 3. This new development uses laser light that controls PD symptoms (only using mice so far).
4. Two pathway circuits have also been discovered that can switch off and on extra movements using laser light.
5. They may be able to take care of the dyskinesia problem using the new laser light technique.

Some not-so-good news for me is: the laser treatment has only been used in mice, I can't be in the trial using transplanted fetal tissue with the seritonin cells removed (due to the fact that I had other cells transplanted 10 years ago), and finally - this research is in the UK and will take a while before the US tries it.

But both articles have good news in that a 9-year-old halted trial may be restarted! And researchers think they can fix the runaway dyskinesia, which is why it was halted! That study shows that its effect lasts 16 years! And if we have anything in common with Mickey and Minnie Mouse (aka mice), then the laser treatment provides hope for treating both PD and side effect symptoms of long-term L-dopa usage (dyskinesia) !

It's still clear as mud, Laura, but I tried.

Until then I will wait, patiently flailing with dyskinesia, and as Mickey would say, "See ya next time, boys & girls!" lol

[lindylanka]

Doesn't this finding relate to an over abundance of seratonin cells in the transplant area, a side effect of something intended to do something different......

I do not know what to think of this, except it does not seem to be a primary outcome of the research, who knows what will happen when they try to repeat these results, it all seems a bit haphazard. And if seratonin is what we are lacking, well we know there are drugs that get seratonin working in the brain, there will be plenty of people who have at some time or another taken SSRI's so why haven't declines in physical function, and huge increases of dyskinesias been observed in patients............

The way this has been presented is dubious, but I won't rubbish it in case it is something important, more than a few things have been discovered by accident........

Nevertheless............

hmmm

it does seem as clear as mud...

Lindy

[pegleg]

I may be wrong, but read that part again about seritonin. I believe too many seritonin cells were introduced with the transplanted tissue. I take that to mean that too many S-cells were the cause of the runaway dyskinesia. Too low seratonin cells results in depression.

I found this from the internet:
Doctors often treat patients who are depressed with a combination of therapy and medication, the most popular of which are selective seratonin reuptake inhibitors, or SSRIs. These drugs moderate the flow of serotonin, a key brain chemical that has a direct effect on mood. The best known is Prozac; others often prescribed are Paxil, Lexapro, Celexa and Zoloft


SSRI's are defined:
SSRIs block reuse of serotonin by cells that produce serotonin, leading to higher levels in the brain. Low levels of serotonin are associated with depressed mood.

Read more: Definition of SSRI | eHow.com http://www.ehow.com/facts_5601333_de...#ixzz0tO3Ml6qf

Read more: Best Way - Treatment for Depression Pain With SSRI | eHow.com http://www.ehow.com/way_5541073_trea...#ixzz0tO2UVSyn


Peg

[soccertese]

my take away is great! they are going to restart the research. from what i remember, the foetal transplants worked in a lot of patients, especially those done in canada.

older article on transplants
http://www.neuraltransplantation.dal...ne_neurons.pdf
http://focus.hms.harvard.edu/2005/ju...eurology.shtml

[lindylanka]

Oh, I went and changed the bits around in my reply because I thought I had got it wrong, seems the initial way round was better! I completely confused myself....

And does that mean that they will attempt to lower seratonin to stop dyskinesias - and will we wind up terminally depressed! The mood alterations with ldopa are bad enough.......

I still don't know how I feel about this, Peggy, because they are saying now that they transplanted too many seratonin thingys, didn't they know that at the time, or did they think it didn't matter because seratonin is a 'good' thing, or is this the way they rationalize the presence of these cells and the effect they are having.......... what if it is like some of the other implant stuff like the stem cell inplants in the kidney, where the body itself responds by creating something different, a new situation.

With stem cells in the kidneys there are previously unknown cellular tangles, and nobody even knows what they will do, they are not mimicking known tissue they are doing something unknown..... a lot of this is so uncharted

They are explaining the seratonin effects this way after the effect.......

Like setting out to make a chocolate cake and coming up with banana bread.

There are lots of unknowns, and science is just, after many years of being allowed a total free rein on how it presents itself, admitting that it does not know all........ I am more impressed when I can see patients, real people experiencing improvements. To me that is the proof that something is really working, the take up thy bed and walk thing. I am all for scientific rigor, but it seems to make unexpected leaps of faith some times, and gets bogged down in itself at others. And so many who are waiting and hoping...

Never mind, I take your word for it that this is a good thing, but there is still that niggle that says that this needs to be looked at with the right kind of rigor.....

Lindy

[LindaH]

The article citation: Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson’s Patients with Neural Transplants Science Translational Medicine, 30 June 2010: Vol. 2, Issue 38, p. 38ra46

The full text of the article requires a subscription, but the abstract is available here:
http://stm.sciencemag.org/content/2/38/38ra46.abstract

ALSO SEE the supplementary material including videos of the 2 patients – after a placebo treatment and after the administration of 5-HT1A agonist . The videos are available here.

http://stm.sciencemag.org/content/2/38/38ra46/suppl/DC1

They are pretty amazing , although might be painful to watch by those who are also plagued by dysinesias. But the improvements after serotonin agonist was administered are remarkable – reminds me of the videos of the GDNF patients


The headlines all oveer the Web, like “ With Mystery Solved, Promising Treatment for Parkinson’s Disease May Return” are from the media not the researchers. Some reviewers are suggesting caution – since this study involved only 2 patients, and they say the results cannot be generalized to a treatment for everyone else’s dyskinesias.

But still, it seems there must be some connection. Hoping this finding will open the door for further research on the role of serotonin in “everyday” dyskinesia and possible treatments for all of the PWP suffering with them, as well as reviving the fetal cell studies.

[imark3000]

I thought it is a new thing which identifies and genetically marks the exact brain circuits (cells?) which control movements and developing the abilty to control them by laser light.
What cought my attention is the claim that the treatment does not involve dopamin in any way and thought it seems to be an attempt outside the "dopamin box".

I think the following article provides some additional clarification:

http://www.sciencedaily.com/releases...0707131357.htm

"We found that by activating the 'stop' pathway we could mimic Parkinson's disease. But what we really wanted was a strategy to treat the disease symptoms." For this, Dr. Kreitzer and colleagues turned to the "go" pathway. "We thought that by activating the 'go' pathway, we could re-balance these brain pathways and directly restore movement, even in the absence of dopamine." The strategy worked even better than expected. "We generated mice that lacked dopamine, and these mice showed many of the same symptoms found in humans with Parkinson's disease. But when we activated the 'go' pathway in these mice, they began to move around normally again. We restored all of their motor deficits with this treatment, even though the mice still lacked dopamine."

Imad