Saturday, 9 November 2013

Remyelinating Trials are coming

In the last couple of weeks, studies have seen people go hunting for remyelinating drugs in high throughput screens and this has provided dividends and some candidates. I have heard of others and trials are on their way...exciting another age is beginning.



8 comments:

  1. Since degeneration/grey matter damage happens even in the earliest stages, how helpful do you think remyelination will be?

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    1. Deal with remyelination early too along with inflammation and maximise the potential benefit.

      Demyelination is a know problem, so if we can fix it it must be good, to a poor old Shiverer mouse (which does not make MBP and does not myelinate) effective myelination is the difference between life and an early death

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  2. Mouse,

    Thanks for this - i have seen mention of various trials relating to remyelination. Have any of the potential agents been tested on mice? I haven't seen any research papers about mouse trials. I these agents do encourage remyelination what sort of benefits will we see? I'm assuming rrms patients will have to stay on their dmt. Silly question - is myelin constantly replaced?

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    1. All the agents have been tested on mice some have been published some have not and so we will have to wait and see what the identity of the drugs are, but they have already been used in humans although new versions could be made to change their side effect profiles.

      You need to read through the blog to see some potential ones
      e.g. http://multiple-sclerosis-research.blogspot.com/2013/10/anti-acetyl-choline-drug-promotes.html

      What benefits I do not get know but would hope some return of nerve function. I saw one trial design and it could look electrophysiologically to see an effect this is the gold standard test in life as the imaging modalities for measuring myelin is nt sufficiently adequate.

      As to trial design I have not seen the full protocols but in my mind it would be silly not to leave people on DMT as you have to dissociate natural repair due to blockage of the inflammatory response and induced repair, although the case can be made that you need repair for remyelination to occur but I could argue that this has been cleared up and there has been a block in the immature oligodendrocytes to mature and make myelin. However the landscape of MS treatments is potentially changing the research is beginning to pay dividends.

      Is myelin constantly being replaced I suspect there is some because you can detect the signals of making myelin in the cells. The half replacement times for some myelin lipids have been calculated at 20 days for some to over a year for others.

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    2. —Scientists at The Scripps Research Institute (TSRI) have identified a set of compounds that may be used to treat multiple sclerosis (MS) in a new way. Unlike existing MS therapies that suppress the immune system, the compounds boost a population of progenitor cells that can in turn repair MS-damaged nerve fibers.

      One of the newly identified compounds, a Parkinson’s disease drug called benztropine, was highly effective in treating a standard model of MS in mice, both alone and in combination with existing MS therapies
      http://www.scripps.edu/news/press/2013/20131009lairson.html

      This medicine contains the active ingredient benzatropine mesilate (previously spelt benztropine mesylate in the UK), which belongs to a group of medicines called the anticholinergics. These medicines block cholinergic receptors in many parts of the body including the brain.

      Benzatropine is used in the treatment of Parkinson's disease and to reduce the side effects of certain antipsychotic medicines

      Dopamine is a chemical substance found in the brain, which is known to be deficient in people with Parkinson's disease. Normally, there is a balance between the level of dopamine and another chemical called acetylcholine. A fall in the level of dopamine results in too high levels of acetylcholine. Therefore by blocking acetylcholine receptors with benzatropine, this balance can be restored. In this way some of the symptoms of Parkinson's disease may be controlled. Benzatropine is most effective at reducing the tremor and rigidity associated with Parkinson's disease, however it has little effect on the slow movements (bradykinesia). It is also useful in relieving symptoms such as drooling, pain and sleep disturbances due to muscle spasm or cramps, mask-like faces, speech and writing difficulties and gait disturbances.
      http://www.netdoctor.co.uk/seniors-health/medicines/cogentin.html#ixzz2i5p3hiE8

      So it would seem there should already be data on a trial done with Parkinson's disease, and maybe with some high dosages that would show if it helped or otherwise, as MS and Parkinson's disease seem to intertwine on some aspects.

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    3. We posted on this work one or two weeks ago

      Parkinsnons disease is not a demyelinating disease and the action in the remyelination study found that targeting muscarinc/acetyl choline receptors augmented immature oligodendrocytes to differentiate and produce myelin.

      The really interesting thing is that another group went fishing for drugs and they came up with the same target. They have picked a different drug to benzatropine. The clinical trial was approved by the FDA last week and they may start in a month.

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  3. "exciting another age is beginning.". Will this help people who have had MS for many years? For example are wheelchair users and those who have lost a lot of 'grey matter' going to be able to walk again and kiss bye-bye to Uhtoff's phenomenon.

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    1. If there is demyelination the hope is that it will remyelinate. Experimentally these agents have not been tested in a long term demyelination context and it will not rrpair grey matter nerves that have been lost. As to level of efficacy. I do not know we will have to wait and see.

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