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07-07-2012, 05:56 PM | #1 | |||
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http://www.burrillreport.com/article...esponses_.html
...Skin cells collected by the researchers from patients with genetically inherited forms of Parkinson’s and reprogrammed into neurons showed mitochondrial abnormalities and responded to different treatments in different ways depending on the type of Parkinson's each patient had. The results of the research suggest that induced pluripotent stem cells, which are adult cells that have been reprogrammed to behave like embryonic stem cells, could be used to help define subgroups of patients for clinical trials, says the NIH. Using those induced pluripotent stem cells-derived neural cells as sensitive models for measuring vulnerability to chemical stressors and responses to candidate neuro-protective molecules, say the study’s authors, may help to identify causes of Parkinson’s disease and potential new drugs and treatments to fight the disorder...
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In the last analysis, we see only what we are ready to see, what we have been taught to see. We eliminate and ignore everything that is not a part of our prejudices. ~ Jean-Martin Charcot The future is already here — it's just not very evenly distributed. William Gibson |
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"Thanks for this!" says: |
07-07-2012, 08:38 PM | #2 | |||
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Finally, admitting that there is no one form of "PD"...
This is encouraging! Laura |
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07-08-2012, 04:54 AM | #3 | ||
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It would be interesting to know about the neuroprotectivess of other things also. Why don't they also check Azilect, Creatine, other anti-oxidants, general PD drugs and other meds for their neuroprotectiveness ? The results obtained could be very helpfull for PD patients, given the big uncertainty there is currently concerning neuroprotectiveness.
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07-08-2012, 08:25 AM | #4 | ||
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Magnate
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diego, they do test neuroprotective agents all the time. they test them all the time in vitro and on mice/rats.
they did a major study on azilect people taking all pd meds continue to get worse, that seems to tell me pd drugs are not very neuroprotective. coq10 had a major neuroprotective study, there is a new one. they have done studies on selegilene being neuroprotective. and vit c and vit-e.. there are dozens if not hundreds of papers on potentially neuroprotective agents. pd'ers take all sorts of other drugs and supplements, i'm sure a neuro would notice a patient that wasn't progressing as expected and do a little digging and most pd'ers and their family members would mention this to their neuro. everything that's been tested on humans has failed and these are very long trials. i would speculate researchers are looking for a way to test cell lines, etc. or some other way to test neuroprotection and haven't developed it yet since it's very tough to detect small benefits in a heterogenous population. just speculating. major problem is by the time you are diagnosed, you have lost supposedly 80% of your dopamine neurons, neuroprotection might have to do an impossible task, that is prevent anymore neuron loss in a person at an age where even normal people lose a few neurons yearly - we would all get pd if we lived long enough. that's why there is so much research at detecting pd as early as possible and susceptible genotypes earlier, when neuroprotection can really be tested and the benefit proportionally greater, and there will be a potentially huge pool of subjects. as dna testing becomes cheaper and eventually everyone gets tested, neuroprotection research will explode, the public will demand it. again, a major problem in all pd research is finding subjects. researchers can spend over a year finding candidates. |
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07-08-2012, 10:14 AM | #5 | ||
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Soccertese, your points are valid points. Though, they can all be discussed:
- they test them all the time in vitro and on mice/rats: And they found lots of things being neuroprotective on mice and rats but not on humans. That's why they should redo these things on these new human neurons. Things like Creatine, Isadiprine, Azilect, ... it is easy to test them on these human neurons and this would lead to much better insight into whether they are neuroprotective or not. At least you can show whether they are definitely not neuroprotective so you don't need to waste resources on them. - people taking all pd meds continue to get worse, that seems to tell me pd drugs are not very neuroprotective: That doesn't mean these things are not neuroprotective. Neuroprotectiveness means that it slows down neuronal death. It doesn't mean it will stop neuronal death completely. So still, al these meds could be neuroprotective. And testing this on human neurons could at least tell us whether they are not. If some med doesn't show neuroprotectiveness at all on these human neurons, then we can almost say with 100 % guarantee that these meds are not neuroprotective. I would really like to see how Azilect does on these neurons. We are having these complicated studies now on a huge amount on patients which take years to see if Azilect is neuroprotective or not. Now, we could finally know it within 6 months if we would test it on these human neurons. - coq10 had a major neuroprotective study, there is a new one: I don't believe these studies. You have different kind of people with their own type of PD. Some progress fast, others slow. They do not make a distinction of this during the trials, mainly of course because they have no clue how to make this distinction. As a simple example, suppose you have an extreme case in which everyone in the group that gets the med has a fast progressive PD form, and in the placebo group you have all slow progressive PD patients ... your study results will be completely wrong. The med might have slowed down the progression of the first group significantly but it hasn't been slowed down more than the people in the placebo group that had a slow progressive form of PD. I realize this is an extreme example, but because these clinical trials usually don't consist of enough people, something similar could occur and lead to wrong conclusions. As you could see from the article of the OP, coQ10 is neuroprotective; while the initial study claimed it could not be proven coQ10 to be neuroprotective. The problem is in the design of the experiments in clinical trials. The only way such trials will detect neuroprotectiveness is if the neuroprotectiveness is incredible. - major problem is by the time you are diagnosed, you have lost supposedly 80% of your dopamine neurons: I don't remember the website, but it is a big and important Parkinson website where I found it. I remember the titles and subtitles of this site are in green colour ... maybe someone knows this website ... but I read on it that last year one of the researchers found out that this 80 % is wrong. There are much more neurons available when first diagnosed than currently believed. - I think the major problem is not the amount of subjects (though it is an important subject) but the fact there are no biomarkers. Even if you have lots of people with PD in trials ... so what ? You can't even measure how they progress. |
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"Thanks for this!" says: | paula_w (07-09-2012) |
07-08-2012, 10:37 AM | #6 | ||
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http://www.dailymail.co.uk/health/ar...sful-mice.html it is coming, do not despair!! |
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07-08-2012, 10:48 AM | #7 | ||
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Magnate
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all these trials use statistics to determine if there is a statistically significant affect in the treatment group vs. the placebo, and they give the probability that the difference is just due to chance. so you are saying all clinical research that relies on statistical analysis is defective? that researchers purposely avoid picking candidates at random and aren't assuming a normal distribution? even trials done over multiple locations and even countries?
of course would be better to test on human neurons and that seems to be the goal but you still have to test on humans, the compound has to get past the digestive system, the liver, the blood brain barrier and to the brain. i stated they have done trials following patients on selegilene and dopamine agonists and found no significant neuroprotection. as far as coq10, after the trial showing positive results from 1200mg/day came out, i'm sure thousands of pd'ers started taking coq10 and if anyone had and sig. slowing of progression it would have been mentioned on this board. |
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07-08-2012, 11:21 AM | #8 | ||||
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Anyway ... I guess scientists doing research on this are aware of how to use this new technique to speed up PD research and waist less money on clinical trials on products that are not going to work anyway. They are more knowledgable than we are. Anyway, this technique is a real blessing for the PD community. I also guess they can use this technique to implant the dopamine neurons in the brain. They only need to fix the wrong gene and the neuron works perfect again. After implantation the neuron will not be rejected because it is the same as the neurons in your body. |
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07-08-2012, 06:33 PM | #9 | ||
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Magnate
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"Statistics isn't magic"
agreed. statistics are used all the time to measure small differences, and what you are comparing in these trials is the natural variability between all subjects vs. the difference between treatment groups. that is, if there is 5% natural variability among all members in the experiment and 10% difference between the control and treatment groups, then you can statistically come to a conclusion on the probability that the difference was not due to chance and at what confidence level. you have to assume you are sampling from a normally distributed population, that most candidates are within the normal range of variability and not skewed at the extremes. considering that many trials include people from all over the country/world, one can assume you are sampling from a normal distribution. most people will be average and a few many standard deviations different. there is research showing tobaco reduces the probability of getting pd, there are no biomarkers, statisticians just survey the data. and yes, i think a 20%neuroprotective benefit could be detected over time without biomarkers. |
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07-09-2012, 04:31 AM | #10 | ||
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You think it is possible, I think it is not. Of course our opinion is not based on exact science. But the current measure used is not good. People's symptom vary a lot during day. Some persons have better symptoms in the morning, others have better in the evening ... so the score even depends on which person you measure during which time of day and also of the researchers subjective assessment. So based on this I think 20 % neuroprotectiveness can't be measured by trials. And then you also have the placebo effect ruining the results of clinical trials even more. All of this causes problems with the results simply because there are no biomarkers at the moment. I just can't believe that till now nothing neuroprotective exists. Like the CoQ10 ... the trials said it wasn't neuroprotective ... Well, actually it says neuroprotectiveness can't be proven, which doesn't mean that it isn't neuroprotective. The tests on these human neurons showed it was neuroprotective. I tend to believe the test on the human neurons much more than the clinical trials. CoQ10 protects neurons. Whether taking it orally is enough for neuroprotection I don't know. But if enough CoQ10 gets into the brain, then it must be neuroprotective. I think it just reduces to a problem of delivery. How to get enough CoQ10 into the brain ? And what are the side-effects of CoQ10 on the human body ? |
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