Thank you for the response. TThe work does seem to be published.
Here is one of the latest abstracts.
The Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre, Kyneton, Australia. [email protected]
For the past 40 years Parkinson's disease (PD) has been intrinsically associated with dopamine (DA) deficiency of the nigrostriatal DA system. One of the fundamental strengths of this theoretical approach is based on a presumed relationship between the degree of DA deficiency and the severity of motor impairment in the disease and its models. However, detailed examination of a substantial number of exemplary preclinical and clinical studies reveals that any such interpretation is overoptimistic and suggests that DA deficiency may be merely an epiphenomenon of a larger process underlying this disorder. Such a conclusion is based on numerous examples of miscarriage of basic principles of good scientific practice including (i) failure to thoroughly examine the adverse effects of DA replacement, (ii) drawing of statistical inference without recognising excessive spread of measure thereby lessening the importance of outliers, (iii) confounding independent and dependent variables within the scientific paradigm, (iv) overlooking fundamental principles of modern pharmacology, (v) confusing correlation with causation in linking cause and effect and (vi) disinclination to incorporate conflicting findings thereby infringing the quintessential scientific principle of tertium quid. This review demonstrates the inherent risks and dangers in the incontrovertible defence of DA deficiency theory and serves to address the ethical problems that emerge from the clinical application of scientific findings. There is increasing interest in new directions for PD research by dimming down the current emphasis on the importance of DA deficiency and its replacement. This would provide genuine hope and a new direction for the sufferers of a most debilitating disease.
Thank you again for this. I have explored more of this and found an overall review paper including a review of the GL Willis et al work. http://www.hindawi.com/journals/pd/2012/767105/ Willis is by no means the only researcher in this field. The trials thus far seem to have been small and not well controlled for placebo and blind.
It does seem that light therapy is fairly well known of and may have value to reset circadian rythmns in PD and older people. It may be of only marginal value to me as I do not seem to have sleep or depression issues so suggesting circadian issue are not a problem. Others may however if sleep patterns, depression or excess of medications are an issue.
Very interesting; thanks for posting!
Browsing a bit on this made me realise that light can also influences one's cortisol levels (which are known to follow a circadian pattern)... and as you might remember from some of my previous posts, I'm looking into the hypothesis that cortisol plays a key role in PD (cortisol controls our body's ability to respond to inflammation and stress and to properly convert sugars into energy; cortisol deregulation has been shown to be associated with PD; and more worryingly, l-dopa meds have been shown to reduce cortisol levels). I'm trying to find out how to best control my cortisol levels in the most natural ways possible (not keen on taking meds like cortisone).
I'm not sure (yet) in what ways light might play a role, but I saw at least one interesting article (http://www.ncbi.nlm.nih.gov/pubmed/15177708?dopt=Abstract) showing that alarm clocks that lit up progressively before they ring to wake up (dawn simulation) help increase cortisol levels. I just ordered one to try it out :-)
Warm regards,
lfs
I sent your information to Dr Willis for comment and received the following reply. Hopefully it will be useful for you. Thank you so much for responding. H
Hi Howard,
Thank you for your email and for your vote of confidence.
We agree that there are many things which remain yet undiscovered about our physiology and PD. Cortisol is one of them.
Could I please make a suggestion, though. WE would not recommend that you use a dawn simulator at this point. Morning light could well interfere with the treatment regimen that we will employ for your treatment.
There is much more to this then changing cortisol and there is a multiplicity of ways to control cortisol secretion and a multiplicity of reasons why it might be out of wack.
So we would recommend that you wait until you visit our clinic to make any treatment decisions.
Best regards
Dr. Greg Willis
Hi Howard,
Thanks for taking the trouble and for sharing the response. I can understand that he doesn't want you to try any "treatment" before visiting - as this could obviously mess-up anything he might suggest. I'm also very interested in his comments that "There is much more to this then changing cortisol" and that "there is a multiplicity of ways to control cortisol secretion". If you happen to find out anything concrete about it that you can share, I would be most interested.
Warm regards,
lfs
Here is a brief description of the light therapy rationale from about 5 or so years ago provided by the Harvad Medical School;
"There are several clues that light therapy might help people with Parkinson’s disease. Experiments have shown that blocking melatonin might reduce the severity of the muscle rigidity that’s characteristic of the disease — and light therapy seems to reduce melatonin levels.
Light therapy may also help with the depression that besets people with Parkinson’s. Australian researchers enrolled a dozen Parkinson’s patients in a light therapy study. They exposed them to bright fluorescent light (1,000 to 1,500 lux) for an about hour each day shortly before they went to sleep.
Then they assessed the effect of the treatment at regular intervals. Within two weeks they observed improvement in bradykinesia (slow movements) and rigidity. Tremors were not affected, but the researchers did document improvements in mood, sleep, and appetite. Light therapy also permitted the reduction of L-dopa and other medicines without a worsening of Parkinson’s disease, according to the results published last year in a journal called Chronobiology International.
A preliminary study like this one with no control group for comparison can’t be leverage into a treatment recommendation. But, as the researchers noted, it does justify further research into light therapy as perhaps a useful add-on to today’s far-from-ideal treatments for Parkinson’s disease."
They have said to me that tremor is now affected but no doubt we will see. They also do now offer a treatment regime. Lets hope it is all good.
No control group?! Then its not science! They say that tremor is affected but without a control group there is no way to tell. It's like I can claim that eating chocolate improved my symptoms. Was chocolate causative? I have no idea because without comparing it to the effect of not eating chocolate there is no way to tell if other factors (that I believe it is working, natural variation in symptoms etc etc etc) are causative. Of course I own shares in Cadbury's so I want you to eat chocolate!
Without a control group or proper, repeated studies it is simply not science. Do whatever you like but please don't dress it in the legitimacy of science. I'm afraid, for now, it belongs in the category of unproven; like standing on your head to relieve your symptoms. Maybe I should set up a web site offering standing on your head sessions, make up some testimonials and charge £1000. Anybody want to try it? There's hope it is all good...
Please read this: http://www.senseaboutscience.org/
dr jonny
Hi Howard: Thanks for that too - I'm not familiar with melatonin, but will try to see if I can learn a bit about it as I'm keen to understand this whole area better!
Hi Dr. Jonny: You raise a very good point, of course. But I personally am not going to discard any leads on areas I find interesting just because a given protocol hasn't been followed (no matter how helpful that protocol might be). Anyway, it's not like we can trust "legitimate" science either. Consider, for example, this rather disturbing quote from an article I read recently:
"A few years ago scientists at Amgen, an American drug company, tried to replicate 53 studies that they considered landmarks in the basic science of cancer, often co-operating closely with the original researchers to ensure that their experimental technique matched the one used first time round. According to a piece they wrote last year in Nature, a leading scientific journal, they were able to reproduce the original results in just six. Months earlier Florian Prinz and his colleagues at Bayer HealthCare, a German pharmaceutical giant, reported in Nature Reviews Drug Discovery, a sister journal, that they had successfully reproduced the published results in just a quarter of 67 seminal studies" (http://www.economist.com/news/briefing/21588057-scientists-think-science-self-correcting-alarming-degree-it-not-trouble)
My personal take is that we need to keep our eyes open and decide what to believe or not for ourselves. I'm sure we'll follow many false leads and make plenty of mistakes, but hopefully if we keep sharing our ideas/experiments with each other - like we do on this forum - we might just be able to identify those few elusive things that might actually help us - after all, there's no scientific researcher in the world that knows PD has intimately as all of us that really have it. If you try out something and tell me it seems to be working for you - hey, I'm going to listen attentively!
Cheers to all,
lfs
Hi ifs
True, science isn't perfect; its slow, obsessed with publishing data first (there's no prize for second place so work is often rushed into print), prone to errors, takes a long time to reach a consensus, often focuses on one or a few genes etc.
What I object to is the lack of a control. That is fundamental to what science is. Without controls there is no scientific data. For example, you want to know what causes water to heat up. First you add the same amount of water to a small container and a large container at room temperature (the variable you are testing is the size of container) but see no increase in temperature. The size of container does not cause water to heat up. Next, you fill two small containers with the same amount of water at room temperature but you put a flame underneath one container (the variable you are testing is presence of the flame): the water heats up! Therefore, the flame is the cause of warmth in the water. If you used one small container and one large container and applied the flame to the larger container it is impossible to see the real cause; the size of container and presence of the flame are both varying at the same time. You need a control to work out what is going on.
That's why personal testimony is not science. It does not identify the causative agent because you need to know if the effect is there when the cause you are testing (e.g. light) is not there. It is really difficult to control for the light studies and that is why the data probably hasn't been published or is weak; it is obvious to the participant which group they are in (exposed to light in the experimental group or exposed to no light in the control group). The people not exposed to the light know they aren't getting any potential benefit and will tend to report no improvement. This shows the need for proper controls.
We can try anything we like (eating chocolate, standing on our heads, shining light in our eyes) but without controls you can't claim it is science or you know that the thing you are taking is causative. This is especially important when you are paying for such a treatment. If the treatment is experimental and in need of further study then the inventors of said treatment should be paying you to take part in a clinical trial. If you pay you are a being exploited in the worst possible way; they are praying on the desperation we all feel for a cure and they are doing this for financial gain. Such people exist. I think dashed, empty hope is psychologically worse than no cure. You may disagree...
dr jonny
Hi dr jonny,
I surely don't disagree that controls are good and that people (knowingly) exploiting others as you describe deserve no respect. On the other hand, I hope you also don't disagree that there's nothing wrong with trying stuff that is untested/unproven - when one is aware of the risks, willing to take them, and goes there with his/her eyes open.
Now that we are on the subject of scientific studies with controls, allow me to also mention that I'm actually a little suspicious that the control groups of PD studies being done might not be all that effective either. Imagine for a second that PD is caused not just by one factor, but by a multitude of factors. For example: imagine that I got PD because I have a high level of inflammation that is affecting my dopaminergic neurons's ability to create dopamine, while someone else got it because he/she has a problem with some enzyme that our brains need to convert l-tyrosine into l-dopa, while a third person got it because of a problem somewhere else, and so forth. Imagine there are say 20 such "problems" that all cause us to have low dopamine activity. Now imagine that you're testing (with controls) a great new med that can actually fix one of those problems. Control or no control, you're not going to get any statistically significant results, right? There will just be too many folks that won't react to that med because their problem is elsewhere. My point is that most studies design PD control groups assuming that everybody with PD will react the same way to the meds they are testing - I personally suspect that for PD that might be a wrong assumption. If my suspicion is true, then we need to design better (i.e., more homogeneous) control groups.
All the best to you,
lfs
Clearly if it is possible, one would like to see a large well controlled double blind trial. Unfortunately the world does not always oblige. These are very costly to set up and run and can take ages in implimentation. Large pharmas are the likely users of these to convince serious investment. The solution then also needs to be able to be patented and also be able to make large profits in the protected period. Science can be based on less goldplated proof and simply be based on evidence howbeit with caution. Medicine has a long history of now realised false remedies. However as long as the downside is limited and realised one needs to allow for opportunity. The world community took 15 years to accept a cure for stomach ulcers. An australian researcher had to inoculate himself then cure himself with an antibiotic to establish to the world that a cure existed. Sometimes the sufferers do not have 15 years.
The stomach ulcer guy won the nobel prize not because he cured himself; he won it because his findings were replicated in properly controlled clinical trials (it was easy to test as the antibiotic was already licenced). I understand the need for a cure and you can try anything you like; but there must be objective evidence that something is effective beyond one person saying "I feel a bit better". The scientific method is slow and prone to error but it is the best method we have of sorting out cause and effect in our complex world.
I find it much more effective to try to understand and come to terms with my PD so I can make the most of time I do have. This is a more effective way of living my daily life (trying to live alongside my disease) than avoiding myself by engaging in a smoke screen of "cures" that is unlikely to offer any benefit and even if it does the design of the study (just me and no control) is unlikely to uncover if the treatment is consistently effective (while your taking X you are also occasionally eating a banana and the banana causes your symptoms to improve but you ascribe the benefit to X)
Researchers at the moment are trying to work out whether what we call Parkinson's disease (the symptoms are hugely variable) is in fact multiple diseases; e.g. Lewy body and non-lewy body PD, early and late? etc. The point about multiple causes highlights the need for proper controls. I would make the point that even if PD is a group of related diseases it was still possible to work out and test that dopamine replacement is effective (but not perfect I hear you say! I agree!). I would guess that the closer a treatment gets to the root cause of a disease (e.g. replacing the nerve cells that are lost or preventing cell death in the first vs light treatment) the more powerful and obvious the effect in clinical trials. What is the best way to test this hypothesis? By a properly controlled scientific experiment!
dr jonny
I think it boils down to personal preferences. I fully agree with you that we're highly unlikely to find a "cure" on our own and that even if we do stumble on it that it will be tough to be sure we did (for the reasons you mention). I also totally respect that in those conditions you - and many others - may prefer to not waist your time on such "experiments" and focus instead on making the most of your daily life. But I guess we are all a little different - and in my case, I prefer to keep trying. It's not like I want to try anything either, but some things resonate more with me than others. E.g., my strongest hypothesis as of today is that cortisol deregulation plays a key role in my PD. I'll keep trying to learn more and more about it (trying to distinguish what is known with reasonable certainty, vs. just guesswork) and what can be done to manage it. Where I feel it's safe enough I'm ready to try a few things to see if they help (I just got my light alarm clock) - clearly it's far from ideal, but my personal preference is clearly to try to do something about my PD and it's not like proper science is giving us any answers right now...
Warm regards,
lfs
Hi ifs
I respect your decision to try and find your own solution. I think we are aiming for the same thing: improving our daily lives. I would be interested to read any papers you have found on cortisol disregulation; how does it cause death of nerve cells?
I'm just a bit concerned that what you are doing isn't really "proper" science (as you call it). But as I keep saying you can try anything you like...
If I may be so bold I think you misunderstand how science progresses; you say that science isn't "giving us any answers right now..." Science works by slow accumulation of data and every paper that is published adds a little piece to the jigsaw. To reach a consensus and to understand a piece of the puzzle takes a long time (Nobel prizes are normally awarded for work that was carried out 20 years before the prize is given;this is because its takes that long for the full significance of a piece of work to be apparent). The media gets it wrong (and does a disservice to science) with the endless string of "major breakthrough", "cure round the corner" headlines. The leaps in scientific knowledge are rare; science normally gradually builds up a picture and this unfortunately takes a long time. So it is true that science is not giving the sorts of answers all PD sufferers want (a comprehensive picture published in one paper that leads directly to a cure) but it is wrong to expect science to give those types of answers. It is all about slow and steady...
dr jonny
Hi dr jonny,
I haven't yet found any proper evidence of causality between cortisol de-regulation and parkinson. So far, I only have a fair amount of what you might call "circumstancial evidence" that cortisol is important, as follows:
1. A few studies (with proper control groups) have shown that PwP have low levels of cortisol. See, for example this one: http://www.ncbi.nlm.nih.gov/pubmed/1851513
2. My own lab results show that I have low levels of free cortisol (apparently because I have too high levels of transcortin: most of our cortisol seems to bind with transcortin, so when you have too much transcortin, too little cortisol remains free to do the stuff it normally is supposed to do; my levels of total cortisol seem to be normal - it's only the "free" cortisol levels that are low). I also have a few lab tests that suggest inflammation, and I obviously have PD too.
3. Cortisol seems to be widely believed to play a key role in the way our bodies' response to stress, inflammation and conversion of sugars and fat into energy (just check wikipedia or google cortisol). I don't fully understand yet how this works nor how exactly it is linked to PD, but I find it suspicious that stress, inflammation, and energy (tiredness) have also been clearly associated with PD. There's also a bunch of other similar "loose" associations that I find interesting - if you google what natural things you should do to get a normal level of cortisol, you find many of the same things that people often mention that sometimes work to alleviate the symptoms of PD (moderate sports; cafeine, etc, etc).
4. There are some claims (which I don't know how true they are) that giving PwP with cortisone helps with their PD symptoms. See, for example: http://www.prweb.com/releases/2012/9/prweb9954106.htm. Note however, that I'm personally suspicious of this approach to increase cortisol levels, as taking cortisone apparently has some important drawbacks (like you get "hoocked" for life, as your body stops producing the stuff naturally) - so I'm not keen on going down this road - at least not with the level of info I have today on cortisol.
5. This article (http://www.ncbi.nlm.nih.gov/pubmed/17414942) concludes that taking L-dopa to treat our PD symptoms also further de-regulates cortisol... which means that if you believe the hypothesis that cortisol de-regulations is a cause of PD... then it makes it even more important to find a way to manage your cortisol levels when you're taking l-dopa (otherwise you might just be treating the symptoms of PD but actually making things worse).
BRs,
lfs
PS. I get that science progresses slowly. It's just that I don't have that much time :-)
hi ifs
Science is too slow for my liking too!
I think you have to be careful how you assign cause and effect. Is cortisol affected prior to nerve cell death and emergence of symptoms? If so then it may be causative for cell death. Or does it go wrong after the emergence of symptoms? Then it is one of the many effects of the loss of nerve cells in the substantia nigra. The stress of being told you have a chronic, incurable, progressive disease may affect cortisol; rigidity of the muscles may cause an inflammation response (I'm speculating here) which impacts cortisol levels. Changing cortisol levels may treat one of the effects of nerve cell loss but it won't treat the root cause of Parkinson's; the death of nerve cells.
Incidentally, l-dopa also treats one of the effects of nerve cell loss (reduced dopamine) but does not treat the root cause of Parkinson's; nerve cells are still being lost. I suppose replacing dopamine is closer to the primary effect of losing dopamine producing cells than (I'm guessing) cortisol is.
Assuming cortisol levels are causative for nerve cell death treating now will probably only slow the rate of loss; unfortunately when we are diagnosed about 70% of dopamine producing nerve cells in the substantia nigra have already been lost. But slowed progressive is better than nothing. But the role of cortisol, if in fact it does have a role, is largely unknown.
More work is needed to untangle the causes and effects of PD. Come on science, get a bloody move on!
dr jonny
