Sunday, 29 March 2015

Progressive MS trials are like buses you wait ages for one and then two come at the same time

Whilst  I appreciate that maybe our car-loving readers may not get the concept of two buses coming at the same time when you have been waiting ages for one, it is funny that this is just what is happening in progressive MS. 

We have to take the 55 bus or the 205 bus each day or walk 2-3 miles (~4-5km) to see the beasties, some times multiple times a day

The idea of MS-SMART trials was started many years ago and the drug candidates were selected based on evidence in MS, some evidence in EAE (Which was all largely irrelevant because EAE studies are not done in a way that they are very informative about protection) and evidence from other conditions. We even tested some candidates in EAE for this approach. They were not found to be very good. This was all done systematically.

One candidate was Ibudilast and this was selected but it turns out that a study is doing this in the USA. (Two studies on the same drug, well it was not possible for technical reasons and so next they come up with Fluoxetine (commonly known as Prozac), which is a selective serotonin re-uptake inhibitor. So it is of interesting that FLUOX-PMS is now ongoing in primary and secondary progressive MS in the homes of people in Netherland and Belgium

Serotonin is removed from the space around cells by a transporter system that sucks it up into cells. So it can bind to serotonin (5-HT) receptors. This can reduce depression. How does increasing serotonin affect progression, well I'm not sure there is some EAE data showing an immunomodulating effect, but as I think that such an effect is irrelevant to control of progression we need some more ideas. Some people think that SSRI may affect astrocyte function,that may affect sodium-dependent glutamate uptake by astrocytes, and the release of lactate, which serves as energy source for axons Fluoxetine also stimulates the release of the neuroprotective brain-derived neurotrophic factor (BDNF) from astrocytes, and may improve cerebral blood flow by dilating cerebral arterioles independent of the endothelium.

Maybe if you are not depressed then you are less stressed and this slows things down.

If you have SPMS and live in the UK, please seriously consider signing up to MS SMART (CLICK), not all sites may be active yet, but it is coming.

Will it work? I have my thoughts, but I don't really know. P.S. please do not ask for my thoughts as a penny or a few pounds is not going to let me part with them

But as DrK reminded me, after a trying week, about a note from the London Underground.

"Anyone who says failure is not an option has also ruled out innovation"

Innovation is the future and we have to be prepared to fail otherwise change will never happen.

CoI: This is nothing to do with me...but I would be very happy if you volunteer to take a drug that may (I won't guarantee it) do you some good.

11 comments:

  1. Good day
    I have anxiety and depression and so far have resisted meds, looking at this surely taking the meds might be extra beneficial, would you suggest people like me take these? Not just for the psychological impact but the potential neuro effects?

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  2. You need to talk to your neurologist as there are meds for depression. Until an effect is proven in MS-SMART, deperession is all that Prozac is recommended.

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  3. Are these trials not including PPMS people?

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    1. I don't think so
      http://multiple-sclerosis-research.blogspot.com/2015/03/multiple-sclerosis-secondary.html

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  4. put your balls on the line mouse Dr me ol son;) which remylation substance shows most promise? Speculation is all im asking for an educated guess we might call it

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    1. I have no idea...but the two company agents is your best bet, the others will get lost in academia and have little chance of being developed rapidly unlessthe powers that be can change the system.

      If the RXR compound works maybe Pfizer will get interested as they have a bucket load of compounds. Biogen has reported some results and their other trial and the GSK trial should finish this year.

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  5. In treating depression different people respond to different medications, and suffer varying side effects to a greater or lesser degree which is partly why there are so many different SSRI meds on the market. What is the underlying rationale/research which has prompted trialling specifically fluoxetine instead of any of the other SSRI drugs available?

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    1. As the neuros doing the study, I have no idea, it wouldn't have been my first choice, but mine wouldn't have come into the reckoning as there are a few boxes in the selection process not ticked and no I will not tell you what it is/they are.

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    2. Sorry MD - I sort of missed out including the first part of my question - which was how did it get picked up that SSRIs may have benefits in MS, and then asked why fluoxetine was chosen from the SSRIs currently available.

      No - I'm not asking you to reveal what candidates you may think should be included, so you can sit back and relax on that count.

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    3. I don't know

      Thanks I'm relaxing:-)

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    4. Anon 11:57
      There's actually quite a bit of data in experimental models of stroke/Parrkinsons that fluoxetine may have neuroprotective properties, maybe by suppressing microglial cell activation. there's one EAE study too, though not in a very realistic model.
      http://www.ncbi.nlm.nih.gov/pubmed/?term=fluoxetine+neuroprotection
      http://www.ncbi.nlm.nih.gov/pubmed/22441536

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