Tuesday 28 February 2012

IGF-2 and its relationship to Dupuytren's Contracture

Today was a hard day, I was not on my feet a great amount but apparently just the thought of going back to play badminton (which I am awesome at by the way) is enough to trigger my foot into going nooooooo. From about 2:30pm today until the end of work I was in pain when sitting that just increased when I was walking and went into overdrive when I was standing. I am not sure what to make of it, on the one hand I really want and need to lose weight but I am not in a position to cycle and I am very self concious about swimming and always get ear infections (though would start using ear plugs if I started again). Does anybody in a similar position have any suggestions? I used to like running but clearly that is so far out of the question it is not even funny. I would also like to know if anyone out there has any questions about the disease or anything that I do? 

Right so with that over onto the science for today (well the light evening reading for me) I will try and keep it as simple as possible and where I can I will try and include some more background information but the main basis for this post is to talk about IGF-2 and its relationship to Dupuytren's contracture. Remember I am not an expert and I am not a doctor but I am a research scientist so I would like to think that I have a better chance of understanding these things and maybe explaining them to others than if people just tried to read them for themselves. 

For those who don't know about Dupuytren's contracture a quick google search will show you that it is a disease that is thought to share many things with Ledderhose but it occurs in the hand rather than the foot, in fact it is thought that they are basically the same condition in different parts of the body and many people who get one disease will get the other (though Dupuytren's in the hand is much more common). 

A lot of the information that I am getting for this is coming from Dupuytrens Disease Related Hyperproliferative Disorders chapter 20. 

So IGF2 is an insulin like growth factor, all this means is that is a protein that is a bit like insulin and it circulates in your blood stream. The IGFs are known to play a role in many different life processes including ageing and growth and are far to complicated to get into here and now (but feel free to ask me questions as I actually know a bit about that). Anyway it has been shown that IGF2 in particular has a role in collagen production. Collagen has been shown to be one of the main components of the lumps that form in both Dupuytren's disease (DD) and in Ledderhose disease (LD) so of course that there maybe a link between IGF2 and DD and LD is worth looking into. 

Things are not as simple as more IGF2 means more collagen. IGF2 is regulated in the bloodstream by IGF binding proteins or IGFBPs which typically stop the IGFs from binding to their receptors. IGFBP6 in particular is thought to be involved in IGF2 regulation as it binds to IGF2 10 to 100 times more than it binds to IGF1. Anyway what people have shown is that IGFBP6 which remember stops the IGF from performing its function is actually at lower levels in DD tissue. So think about that, IGBP6 which lowers levels of IGF2 is decreased, that means that there are higher active levels of IGF2 and now remember IGF2 causes collagen production and what are the lumps in DD and LD made of, Collagen. 

What some researchers have actually done is grow cells and look at them contracting, they have then looked at cells from DD patients and as a control they have used cells derived from non-diseased portions of the hand. What they find is that if you add IGF2 then you increase the contraction and if you add IGFBP6 then you decrease the contraction. They have also looked at something that is upstream of IGFBP6, so by this I mean that they look at something called TGF-B1 and this is known to decrease the levels of IGFBP6 and so increase IGF2 and so increase levels of collagen and in this case find that there are increased levels of TGF-B1 in DD cells. 

So what is the relevance of all of this? Well what do you think might happen to a DD or LD patient when you add IGFBP6 to the lump? Well of course you should decrease the levels of IGF2 and therefore decrease collagen production and therefore ease symptoms of the disease. Sounds good to me and I hope that the picture below helps to explain this to people that have not followed the above which is quite complicated. 





8 comments:

  1. So has treatment been attempted on DD patients using this research?

    The Old Bag

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  2. As far as I am aware this has not yet been attempted but perhaps one day it will be used in a cocktail of proteins that all target different parts as I know that there is an injection that is used to directly target the collagen.

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  3. Which country is this research being done in?

    The Old Bag

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  4. Great article, thank you.

    How would we discover if there are any clinical trials?

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  5. A friend who has both LD and DD and who is married to a cardiac nurse, told me that they know of a doctor who says there's a relationship between DD, LD and heart valve problems. I have just been diagnosed with DD and a regurgitating tricuspid heart valve.

    Do you know anything about this?

    I can't find anything on the web linking heart valve problems to these other issues, but I did find a mention that myocardium is subject to thickening as is palmar fascia. I don't know if that suggests that a heart valve can be damaged through thickening like the lump in the palm of my hand, or not.

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  6. So first of all in response to the old bag this research was done in Canada and this leads me to answer the clinical trials and the answer is I do not know if there is anything out there but I have tried having a look using google searches etc and I am unable to find anything (at least in UK) and that is any kind of clinical trial not just the stuff mentioned above. The research I have mentioned is still quite new and any sort of human trials would be a while off (at a guess) but I was looking for LD not DD.

    I have not heard of any relationship between DD/LD and heart valve problems, I guess if there is some tissue that is of a similar composition to that in the hand / foot then there is likely to be increased susceptibility to heart valve condition. However one of the main theories at the moment reckons that trauma is a key trigger to DD/LD such as slight tears caused by over stretching or standing on a stone bare foot etc and I think that these would be much less likely to occur in the heart. I need to go to work soon but if I get a chance later I will try and have a more in depth look and see I can find any research that suggests a link.

    Nona have you or your friend considered joining the LD forum (first link on the helpful links page on the right) as although it is aimed mainly at LD we are just trying to build a community of people that are talking about the disease(s).

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  7. I'm currently researching this for my Dad who has DD and a past history of frozen shoulder. He's been bed ridden for about 5 months with feet problems and I think it might be LD.

    Anyway, do you know anything about tryptophan degregation? When the IDO enzyme is activated tryptophan degrades down the kynurenine pathway to produce various neurotoxic metabolites which activate NMDA receptors causing pain, sleep problems etc.

    One of these metabolites is 3-HAA which "which enhances TGF-β expression from DCs [dendritic cells] and promotes Treg differentiation."
    http://www.ncbi.nlm.nih.gov/pubmed/20944000

    I'm currently awaiting the results of Optimal Nutrition Evaluation test by Genova Diagnostics which should hopefully shed some light on the matter.

    Diindolylmethane (DIM) from broccoli is an IDO-inhibitor so may well work. Also gut bacteria are required to convert glucosinolates in broccoli to DIM so I've been working on trying to get beneficial bacteria into his diet via fermented food and drink.

    This guy and his girlfriend had amazing results from DIM despite the fact they had very different symptoms, he's done a lot of good research on the subject and it may be useful.
    http://forums.phoenixrising.me/index.php?threads/xeno-estrogens-link-to-cfs-fibromyalgia-success.17874/

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  8. Thank you for getting in touch.

    I hope your Dad is ok and that you find something that helps, if it is Ledderhose then all I can say is that radiotherapy worked so well for me.

    I will certainly try and find some time to look through the information that you have shared and if you want to talk about it then feel free to e-mail me at the address on the right.

    Thanks again.

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