Wednesday, 1 July 2015

Unrelated Blogger Comments July

If you want to say something unrelated to the thread this is the place for you


114 comments:

  1. I see that Mouse sneaked a knights post on the blog late yesterday while Big G was attending yet another MS conference. I thought Mouse was going to stop this silly teasing. I think it's time to tell us what all the Knights posts were about.

    ReplyDelete
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    1. Not yet ;-)
      Its not a tease but a report/journey can you remember when it started?

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    2. ps remember everybody what happened at the research day stays at the research day :-)

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    3. Mouse,

      You need to cut back on your drinking - you keep posting your comments twice.
      I know you like keeping secrets / teasing wheelchair bound MSers. Really is time to spill beans. I wasn't at the research day and am desperate to know what was spilled (apart from your can of Tenants Extra).

      Delete
    4. Phone posting is a problem.

      This is not teasing and as you know the research day was videoed and put on youtube for the world to see. Sometimes good things come to those that wait...sometimes they don,t

      Delete
  2. The Tische MS centre in New York is undertaking a novel stem cell trial and reporting interesting results (small numbers of patients).

    http://tischms.org/news/june-29-2015-tisch-ms-research-center-new-york-delivers-additional-encouraging-results-phase-i

    This doesn't look like a dodgy stem cell trial in Ukraine or China. Is it a proper research establishment? Would welcome your thoughts.

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    Replies
    1. lets hope it is good. here are details of the trial
      NCT01933802

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    2. I am a patient at this center, the research work is real and amazing.

      Delete
  3. This is the only part of the blog that gets my goat
    Why would you tease and or imply news whether good or bad to people with Ms? Or readers of this blog in relation to Ms?

    What you do regarding bringing info to people is brilliant, but this is really a little much in my opinion

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  4. This not teasing simply a chronicle. If you watch a TV series can you not wait until the last episode...I am sorry there is not a DVD out yet.

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    Replies
    1. So is friday when the announcement is due?
      I can only assume it's related to your sodium channel blockers or charcot, but from what you've suggested charcot looks a bust?

      Delete
    2. No and this is the problem you are reading things that aren't there or said stop beating yourself up.

      As I have said many times, the Charcot will be reported when it is reported and is nothing to do with me, the sodium trial will be reported when the paper comes out

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    3. Something tells me that MD wouldn't tease us about soul-crushing news - there's already plenty of that without the wait. I'm sure it'll be something of interest to PwMS, or perhaps even some good news. Either way, I'm content to wait until Friday. (Maybe the news is that they decided to add the cup holders to that abomination after all. If so, put me down for one).

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    4. I'm sulking now and so there will be no knights post on friday,

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    5. Glad you are sulking. I'm fed up with the knights posts and with the delays with the charcot project results. If you are doing something interesting - tell us. Even if it fails we are grateful that you let us know what you were up to. The knights chronicle ends. I may have to write a strong email to Prof G resulting in the closing down of your mouse lab. All you'd have left to do are boot fairs to sell your heavy metal albums. You'd appear in Benefits Street - exProf using benefits to pay for his binge drinking.

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    6. Understandable under the circumstances . . . . how about telling us a little about the knight's squire while we wait? :)

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    7. Great Anon 727, now you've done it. All your braying has chased the mice right out of the lab.

      And here I was prepared to woo MD by offering to patrol the alleys around Mouse HQ for stray tomcats for a full YEAR. 3.6.5.! I guess there's no point now - nice one.

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  5. I don't really know who to best direct this question to, but I get a squeezing/tigthening on the temples. Is this an MS symptom or to do with lesions in the head? Does anyone else have this???

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  6. “There is increasing evidence,” Dr. Gow said, “To indicate that autoimmune attacks on the central nervous system may be a secondary event rather than the primary cause of MS. This indicates that researchers must cast a broader net to test new ideas and develop alternative models that could shed fresh light on MS etiology.”http://multiplesclerosisnewstoday.com/2015/07/02/national-ms-society-awards-wsu-professor-grant-to-develop-new-ms-model/ New model focuses on metabolic abnormalities as opposed to autoimmunity. I realize that this blog has posted on this topic.

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  7. Could this be why buotin has been succesful albeit arguably so?

    ReplyDelete
    Replies
    1. why does it only affect 10% of people?

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    2. Biotin is really beginning to get on my nerves.

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  8. Is there any explanation why T-cell depletion with ATG failed in MS?

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  9. What is the thinking regarding the sodium channel blocker avenue? How quickly will the previous succeses get to the patient or would you guys be prescribing off label now

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  10. I've been looking at the sodium channel blocker work you've done and the proxi trial, I see your theory on these as an add on therapy
    I also saw omega 3 has been used previously to aid sodium channel blocking. Would this explain why it has been suggested in Ms?

    Also carbamazepine is used as a neuropathic pain treatment, based on your results so far would it not be beneficial to put your patients on carbamazepine as a 'pain treatment' with the possible benefit of neuroprotection?

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    Replies
    1. Our medics been trying to recruit pwMS for the PROXIMUS trial to look at oxcarbazepine as a neuroprotective agent but the take up has been very disappointing. As it stands we may never know if this will be a viable treatment for progression or not. Shame.

      Delete
    2. Maybe you should put PROXIMUS in the cupboard and find another way, stop crying over it? (And don't blame me for not volunteering - I live at the other end of the country.) What's this about omega 3?

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    3. Giving up is not an option. This needs to be done.

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    4. I agree MD2, I wish I were in a position to help drive this trial. Alas, I'm an ocean away, and far out of reach of Proximus. :( But please keep trying.

      Question about your choice of oxcarbazepine, though: Did you select it purely because you anticipate it to be much more efficacious than phenytoin, or do you also anticipate fewer side-effects than other sodium channel blockers? It looks like Oxcarbazepine has a much lower side effect profile in the general population. Is this anticipated to be the case in pwMS?

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    5. We tested a number of different compounds phenytoin was the worse oxcarbazepine was the best in EAE. It was also predicted to have better side effect profile as you say

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    6. Where are the details for the trial? What dosage and frequency is suggested?
      Am I right in thinking it's been used to treat anxiety too?
      I'll quite happily personally trial it

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    7. we would not endorse any personal trialling as your testimony would not be valuable.If you fulfill the criteria then please volunteer, if not please wait for the results

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    8. Maybe one reason for the low take up of Proximus is the fact that people don't fit the criteria... I am one example :-(

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    9. Yes the neurofilament level for inclusion is too high and requires a protocol change

      Delete
  11. Might it also explain the reason these guys are looking into a Parkinson drug in phase three for neuroprotection? As stated here?

    http://www.ncbi.nlm.nih.gov/m/pubmed/23518709/

    ReplyDelete
    Replies
    1. Hi Kris
      Yeah, same idea, the drugs their using are similar to phenytoin. Trouble is with Parkinson's vs MS is with Parkinson's on diagnosis it may already be too late to make any meaningful intervention as so many of the dopamine producing neurons have already been lost. The same can't be said for MS and the window of opportunity is much larger.

      Delete
  12. That study above is worth looking at, especially the micro glial route and the increase in glutathione which I think is the balance to glutamate which I think has been implicated too, as being high in ocd patients, ocd has been known to kick up after Ebv
    It's a Full circle!

    I agree it's a shame regarding proximus maybe you need to blow your own horns a little more regarding the potential of the treatment and other studies showing such

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  13. I could give you more info in this which no doubt you already have

    http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=131079&XNSPRACHE_ID=2&XNKONGRESS_ID=140&XNMASKEN_ID=900

    This is an interesting study same process I think but an earlier one

    https://books.google.co.uk/books?id=1lCuuUCnblwC&pg=PA193&lpg=PA193&dq=carbamazepine+microglia&source=bl&ots=XyZiIWVOOf&sig=L35xzct7YOHPQ6HSGM41Q3dHhIM&hl=en&sa=X&ei=_lSWVZa2M4zA7AbPyqKQAw&ved=0CEMQ6AEwCQ#v=onepage&q=carbamazepine%20microglia&f=false

    That one is a general citation of evidence supporting your theory, including cell infiltration following carbamazepine withdrawl in EAE, which could be a slight worry as it shows these therapies would need to be a continuou therapy

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    Replies
    1. The second study you describe showed that high doses of carbamazepine suppressed inflammation rather than being neuroprotective per se. So it's not surprising the disease rebounded once the drug was removed. In our experiments we give neuroprotectants such as carbamazepine at a dose that doesn't stop the inflammatory attack so at remission any improvement is due to true neuroprotection rather than just reducing inflammation.

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    2. Importantly in the Lamotrigine trial in humans there was was no rebound in humans, so unfortunately an expected result that happened in EAE made them not do the trial in progressive MS about 7 years ago...opportunity missed

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  14. Gotya
    There does seem to be a lot of supporting evidence regarding the sodium channel
    Blockers though?

    Isn't fluoxetine and the Ms smart trial aimed glial activity which this takes care of also? A double edge sword for you Knights ha
    What is the dosage in the proxi trial?
    Is there any reason why the proxi trial is only for spms?

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    Replies
    1. PROXIMUS is for early MS where the DMT is not stopping neurofilament production

      Fluoxetine has a different mechanism of action

      P.S. ProfG is not a knight

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    2. That's neurofilament production as in detection of free neurofilament in CSF indicating neurodegeneration is occurring. if the trial was positive there's no reason it shouldn't be tried in SPMS or PPMS.

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    3. Here they find no effect for Fluoxetine in Progressive Ms Patients

      "The Effect of Fluoxetine on Progression in Progressive Multiple Sclerosis: A Double-Blind, Randomized, Placebo-Controlled Trial"

      http://www.hindawi.com/journals/isrn/2013/370943/

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    4. The trial was 42 people so 21 on drug but as an unanticipated low rate of disability progression in the placebo group decreased the statistical power. At least 200 patients would have been needed to detect a 50% treatment effect. This trial shows that fluoxetine was generally well tolerated, but no assumptions can be made about a possible treatment effect

      Delete
  15. It's all about neurofilament then?
    Am I right in thinking carbamazepine is used to treat neuralgia such as Lhermittes tn etc?
    I was wrong earlier too, the Parkinson's drug has been approved now for the use as stated, is this another case of repurposing of drugs being an issue or do you have a more preferred treatment as opposed to the Parkinson's drug?

    Also this one for prof g, if you had or have a level of confidence in the sodium channel blockers, would you not prescribe this as 'pain' treatment

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  16. Sorry, you may have answered somebody earlier regarding this, but I was hoping that the results from the Raltegravir trial were to be published by Q2. Have you any updates?

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  17. I got my neurologist to prescribe Lemtrada, but getting an appointment with a new PCP (because previous one is moving out of state) who is going to be around for four years is ... a pain and a half. Must keep going, however. I'd love to hear some advice about not freaking out a PCP since my insurance requires the PCP to order the blood/urine tests. What should I be doing?

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  18. My parents and I didn't know registrar means trainee for over a year. I didn't have much experience with medical professionals and hospitals.
    When I look at some of my hospital letters that state the medical professional's name and rank i.e registrar. It would have been very very useful is it was highlighted in the letter that registrar means trainee and is someone not qualified or experienced.
    The title registrar is a fancy name and not lay persons terminology. My father even thought it meant a medical professional quite senior and with much experience. He has seen many doctors at the hospital himself.
    It is unfair on inexperienced patients who don't know their condition or medical terminology.
    If I had a suspected serious medical condition and all I was offered at the hospital was to see a registrar I would not be happy or confident one bit.
    I would feel ok about it if I had reassurance a consultant would examine me after the registrar. I would also feel ok about it if I had some medical knowledge and experience with hospitals.


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    1. A registrar is highly qualified with many years of experience behind them. 5/6 years med school, 2 years foundations, 3 years speciality training and then 5 years registrar training then they become a consultant. Many take 3 years out to do a PhD so in some cases more up to date with current research than the consultant.

      Delete
    2. All the Registrars I saw when first diagnosed are all eminent Consultants now. They knew their stuff, they were excellent. When I eventually did see my Consultant, he knew all about me. Whilst we're on the subject of trainees, the GP Registrars I've seen when other patients refused, have been brilliant.

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    3. Well it's nice to hear a positive comment for a change ;-)

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    4. I second (or third) this, registrars are a lot more trained and experienced than a senior house officer. And the ones I've seen over the years have been excellent. And sometimes it is because there are no consultant vacancies that they remain registrars, not from want of experience or skills. Even Holby City has shown this ;)

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    5. Well the two registrars I saw had not done PhD's at the time I was examined by them. They made gross mistakes in my care and sadly I am paying for it. They were not registrars in MS, one was dementia.
      I'm glad you had a good experience with registrars. I am just telling my experience and that I was very very unlucky with my medical care. I was naive and inexperienced then, I am not anymore. I did not know what was wrong with me at the time. MS is not always non-urgent.

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    6. Hospitals need to be transparent and use lay persons terminolgy when they can.

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  19. Sooooo . . . MD. When are you going to stop punishing us good visitors for the behavior of a few bad ones and tell us about the Autobot-body-contraption-machine'a-thingie? Repairing damaged knights. C'mon, mister. I even went out and bought a set of used armor. Sure, I have no idea how to put it on, nor do I have any idea how I'll go to the bathroom once I'm wearing it, but the goal was to be extra supportive!

    Sincerely,

    Squire Dudley.

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    Replies
    1. ".........nor do I have any idea how I'll go to the bathroom once I'm wearing it........."
      Usually, a can opener is provided.

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  20. "Usually, a can opener is provided."

    Now why didn't I think of that?!

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  21. NHS England informed me registrars do not do surgery. Private Healthcare do not use registrars, they use consultants only. Just sayiing how it is.

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    1. A senior registrar did my operation and a mighty fine job he did too.

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    2. I guess NHS England don't know what they are talking about. Beware.

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    3. Senior registrar in surgery is that the same as 'senior trainee'? This is what NHS England sent me:
      https://www.rcseng.ac.uk/patients/the-surgical-team/whos-who

      May be it is different in neurology. May be a neurologist could please explain so it can be transparent. Perhaps a post on it if they have the time to help clear things up. Most grateful.

      Delete
  22. What is the tjinking from yourselves on Dr Voskuhl and her study and trials using HRT for Ms, as a neuroprotective and In her recent trial a neuroregenerator?
    Is it causative that men with this have lower testosterone?
    Would you suggest supplementing, knowing that supplementation shuts down the bodies natural test production?
    Could explain the age degeneration theory

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  23. Hey mices any opinion on this? I know you've touched on mitochondria before and it's suggested it plays a role

    http://multiplesclerosisnewstoday.com/2015/07/08/mitochondria-may-play-a-role-in-ms-development-and-progression/

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    Replies
    1. Yes but this a review article and we don't normally comment on these. There is accumulating evidence of mitochondrial problems in Don Mahad (MS Mitochondrial expert from Edinburgh) to do a guest post on this.

      Indeed we have made a drug that protects mitochondria....the journals aren't that interested as the mechanism in not new.

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    2. So you have a drug that protects mitochondria, you have a sodium channel blocker and a possible antiviral?
      Why not do a combo trial? And if it works who cares which one is doing the work

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    3. Why not do.....about a hundred million pounds

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    4. The sad thing is we can throw money around in aid for countries who harbour all sorts yet we can't look after our own

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  24. MOuse DJocs - a question regarding sedation which I will be having on Monday for endoscopy:

    it will be a mix of propofol and something and I worry that it will make my vertigo worse and for a longer time.

    Do you think it could happen or I shouldn't worry and take the sedative?

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    Replies
    1. I'm sure you medical team will be great and you shouldn't wory, tell them your fears and i am sure they will work to alleviate your fears.

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  25. Neurologists not agreeing on things is this very common? I suspect the answer is yes.

    I had a severe relapse and my MS neurologist agreed with me the symptoms were severe. When my symptoms were discussed with another neurologist (not ms specialist) the symptoms were belittled and not of much importance.

    I am not sure how to understand this now and in the future. Do I just need to accept different neurologists have different experiences of MS patients. So they have different levels of knowledge and understanding of MS?

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    Replies
    1. I've known eight people with MS within my circle of friends and family. None of us are the same. There are a few areas where we can give each other advice, but we have all been affected in totally different ways. I also have difficulties, explaining my symptoms as I have had MS all my adult life, I have no idea what is normal. A friend newly diagnosed may mention something I've not thought to tell my neurologist. As a patient, I'm not very good at informing my doctors about things that may be relevant.

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    2. Me too. MS all my adult life and early teens. It is impossible to really know what is normal, when I had L'hermittes (before official diagnosis), I was asking friends and colleagues, if they'd ever had this very peculiar electrical sensation in their spine and toes when they moved their head. Most said they had, well unless there is more neurological problems than I realise, they were not getting it. It can be very difficult to know what is 'normal' when all you know for the majority of your life is MS. In the case of l'hermittes and other things such as TN, optic neuritis or balance, I do know that isn't 'normal' but a lot of things, it is impossible to know so I probably overload my neurologist with information, as I try to keep notes.

      Delete
    3. I was speaking to an adviser on the telephone (can't remember what organisation). They said if we feel something is important to tell the doctor we must tell them. Even if the doctor doesn't seem to agree its that important.
      It's difficult as I spoke with a neuro about a list of symptoms I had/ was experiencing, then I gave them a copy end of the appointment.
      The copy of letter I received from that neuro addressed to the next neurologist didn't mention most of these symptoms. There was no copy of the symptom list in my hospital medical records.
      Would it be worth me printing off a symptom list and highlighting on the list it's for my hospital medical records?
      I do have my own file of symptoms.
      The feeling I get time and time again is when I see my neurologist they are only interested in the here and now and not past symptoms or past examinations.

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    4. I've had a number of serious illnesses as well as my MS. This means I have to repeat my harrowing history each time I see a new doctor or have to have emergency treatment. I've made up a word document with all my history, that includes medication allergies, illnesses, etc. I keep it up to date, it saves time and it is on various medical records. I still use note for my neurologist, because when I get the clinic letter everything I've said is on there.

      Delete
  26. Mouse Doctor,
    Apparently there has been another case of PML with Tecfidera -
    Are you able to post some more details about this?

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    Replies
    1. http://www.medpagetoday.com/Neurology/MultipleSclerosis/52622

      Biogen Reports Another Tecfidera PML Case
      Non-fatal case is the second one for the oral MS drug.

      Delete
  27. I occasionally come across MSers who report they have twitching (fasciculatons) from their MS. They are informed by neurologists the twiching is not MS related.
    I didn't have that many spasms, I had many fasciculations for months - tiny twiches (body wide) also had a purple left palm of hand from a nasty relapse. It would go very dark purple in the shower - it's recovering. One non-ms specialist neurologist said the purple palm of hand was an autonomic nervous system issue, so peripheral nervous system.
    It would seem my MS has affected my peripheral nervous system.
    I guess the the peripheral nervous system is closely connected to the central nervous system.
    I read that MS is central nervous system only?

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    Replies
    1. I also get fasciculations from time to time. A bit of careful research indicated that sometimes this can be related to low magnesium levels - many people do not get enough magnesium. Low magnesium can also exacerbate muscle spasms.

      I also found that Roy Swank in his writings as a researcher and physician states that many people with MS also suffer from very cold hands and feet and other peripheral circulation problems - I have found this has happened to me - I feel the cold like never before as my MS has got worse, and my hand and feet are always cold and purple (my MS has caused quite bad loss of sensation in my feet and they seem to think that even a slight touch of cold is like dunking them in a bucket of ice). Also now getting some strange Reynaud's type stuff happening with one of my fingers which is affected by MS loss of sensation.

      Has Team G got any information on these strange aspects of MS which they could post? Roy Swank is the only MS neurologist I have found who mentions these types of vascular problems related to MS, but what he describes fits perfectly with the problems I have.

      Delete
    2. I have a foot that goes purple/ deep blue and very cold when I sit down too long. When I raise the foot it returns to normal colour and temperature. It's a relative of Reynauds but not the same called Acrycynaosis and is seen in MS. It's to do with decrease of oxygen to the extremities. I try and have a walk each day to help it.

      Delete
    3. Anon at 10.56am
      Thank you - I've done a bit of web research and it does make sense and fits with my problems (although my hands don't sweat excessively). Elevating my hands does not change their discoloured appearance much but now that you mention it I have noticed that if I am dong some things that actively use my hands (though not typing) it does seem to reduce a bit. However, in cold weather it is constantly present even if my hands don't seem to be particularly cold. Once again the Barts blog comes up with useful info!

      I did find a couple of references to it being related to MS. It would be interesting if neurologists started to gather some data on their patients and see how many people have this condition with their MS.

      Delete
    4. I developed a slight circulation problem in my left foot - my weak side. My physiotherapist identified this as being caused by the reduction of movement - flexing the muscles is necessary allow the valves in the veins to work properly and to stimulate good blood circulation. My problem was cured by using a "wobble cushion" to flex my feet whilst sitting and using an FES device on my left leg whilst walking. So in my case at least, no nutrient deficiency or similar was implicated. It was purely a physical issue caused by lack of movement.

      Delete
  28. Mouse Doctor, what's your opinion about the following new?

    Nutra Pharma has filed an application with the US Food and Drug Administration (FDA) for orphan drug status for its investigational drug RPI-78M as a treatment for pediatric multiple sclerosis (MS).

    http://multiplesclerosisnewstoday.com/2015/07/21/nutra-pharma-working-pediatric-ms-treatment-based-venom/

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    1. Ha ha, perhaps the snake venom I use on my face is not just an expensive load of cobblers, afterall;)

      Delete
    2. Interesting,

      I'm not sure I would buy this as an orphan disease and whilst the aim is for paediatric MS and there are fewer than 200,000 Americans at any given time, it is simply MS in children and it is just MS and MS has too many people for it to be an orphan disease.

      Maybe they have a nod from the regulators but if they can do this then they can make primary progressive MS and orphan disease and lower the bar for someone to develop a treatment e.g. one trial only. However, people have argued that progressive MS should get orphan disease status, but I think the regulators did not buy this maybe the FDA is different.

      Next this is a new drug. Are you going to allow it to tried in your child before it is shown to be safe in adults and being a detoxified neurotoxin....i.e. it carries the baggage of neuro (nerve) toxin (killing) as does venom and will scare parents off I guess.

      Next to the target and there is not enough published research on the target to know what they are aiming to achieve a DMT and immunosuppressive, a symptom control agent, or a neuroprotective. There is obviously some unpublished EAE data and it has been reported on web (not the company site) that it affects gamma interferon, which we think worsens MS.

      According to receptor pharma they have finished phase I and are ready for phase II, but in what context as a DMT or a symptom control agent. This is all blurred

      This a company press release for something maybe cash to do phase II trial and until there is some published data this is not worth further comment

      Delete
  29. http://finance.yahoo.com/news/biogen-slashes-2015-forecast-ms-drug-sales-disappoint-114926337--finance.html PEOPLE TAKE YOUR MEDS...the shareholders are not happy!

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    Replies
    1. BIIB stock is getting hammered, down 20%. MS business is slowing down.

      Delete
    2. Maybe someone has leaked the ocreluzimab trial data and the news is that good:-) or maybe it is Lily and the Alzheimer's drug.

      Insider dealing?

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    3. And Biogen R&D boss Doug Williams just left the company to work in a new startup:
      http://www.xconomy.com/boston/2015/07/10/biogen-rd-chief-doug-williams-leaves-to-run-new-cancer-startup/
      What does he know that we don't?

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    4. P.S. Also the sales of Tecfidera were les than expected.

      According to Bloomberg Sales of Tecfidera, which treats MS, were $883 million in the second quarter, below analysts’ estimates of $909 million, so lack of $26,000,000 profit wipes billions of the stock price.

      Delete
  30. An MS Research Centre in New York has shown that CSF fluid injected into mice from progressive MS patients will call CNS lesions to appear. This does not happen with CSF from normal controls. Also it happens in a small percentage of people with RRMS. I do find this interesting as if they could find out what is the difference between the CSF fluid of progressive MSers to normal controls the maybe the can determine exactly what is causing the progression.

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    1. I am guessing it it the story we reported last year from the Tisch Centre

      http://multiple-sclerosis-research.blogspot.com/2014/08/damaging-immune-activators-within.html

      http://multiple-sclerosis-research.blogspot.com/2013/07/factors-in-spinal-fluid-that-can.html

      Maybe they are reporting the damaging cytokine

      Delete
    2. Sorry if this is a ridiculous question, but could you have a CSF "transplant"? Drain what's there out of a lumbar puncture and fill it up with a substitute or a cultured copy of a non-MSer? Like an allogeneic BMT, but with CSF? Or would that not work...?

      Delete
    3. I am afraid not you are producing the fluid all the time so there would be little value.

      Delete
  31. I have been looking back at the past 20 years of MS treatments/research and progress as a base line to see what the next 20 years are likely to bring, and in my humble MS effected body/mind, the future is bleak.

    MS vs Cancer progress - the cancer community are making a lot more progress for treatments/cures than the MS/AI community.

    The past 20 years brought the CRAB drugs, which when you look at the data vs natural progression of MS statistically look very ineffective. (30% relapse reduction is often seen in MS'ers when they are not treated.

    The MAB drugs - progress, but took too long to get to the patients, and safety profile is a concern.

    Progressive (primary or secondary) no progress.

    HSCT - not acknowledged by the MS community and some are dead against it. Is there a hint of pharma influence as this treatment doesn't need their expensive drugs. Safety profile is a concern.

    Cause of MS - you guys are fixed on EBV, next researchers on-environmental, or genetic, or vit D, or all of these things, or none of them. Progress??

    As you guys are much closer to this than this patient, tell me I am wrong on the above and that progres has been and is being made. Cos it looks pretty bleak!

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    1. Yes you are wrong on many levels.

      The past 20 years has brought treatments and more on the way, in some conditions/diseases there are no treatments. If people are on permanent NEDA that is an good result.

      Progressive MS....massive progress...you now have a global alliance on this. There was the need to recognise that this is a different condition and needs a different treatment and we have seen positive results this year.

      Cause...150 genes identifies another 250 to go...I can't let you how many risk factors

      However your first tenet is where the expectation is wrong. In UK there are 400 cases of cancer per 100,000 and 10 for MS and so the budgets going to research reflects this.

      The Cancer UK spent £400,000,000 research in 2010 the MS Society is less than £15,000,000 and when I was on the grant panel it was not unusual to have a budget of £1,000,000.

      If you put £400,000,000 into MS research I guarantee you would have more progress.
      Just give me $5,000,000 and I'll get you more progress.

      Also in cancer trial you have a quick outcome with a hard edge (i.e. survival) in MS these trials take much much longer and many more people

      You are comparing apples with pears

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    2. I find your response helpful, but I hope you will understand that I'm still a little skeptical.

      NEDA - I hope most people think no active disease is s good thing. But no active disease turns into progressive MS, no good, and all of the drugs you have now will do this, so RR NEDA should be the terminology you use. As NEDA is misleading..

      It is well documented in MS that depending on which of the NEDA definitions you use, that the disease can go into NEDA on its own. So saying the CRAB drugs are treatments is true, saying they are good treatments and bring on NEDA, I still don't believe it.

      Progressive MS - what are the results seen this year? A treatment? Or a focus? A focus is good but it took 20 years to get that focus? It took 20 years to get alemtuzumab to the market, and it was a repurposed drug..

      Cause - 3/8 of the way to identifying the genes, so if it took 20 years to identify those genes, we see 30+ away from the rest?
      Progress - potentially, hopeful here for the future.

      UK budgets j can not argue with, however the U.S. Is spending 30 billion USD on MS. With the greatest respect we don't care where the cure comes from, and that sounds like a significant figure to me.

      So let me ask you this, the 5 most significant MS discoveries or progress in the past 20 years (that are widely believed) are?

      By the way - I admire you guys and what you do here, and just the chance to communicate to a MS researcher is a privilege.

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    3. NEDA is no relapse no lesions and no increase in disability. This last one captures part of progression,NEDA 4 no atrophy would capture more.

      The CRAB drugs are simply not effective enough and you cant say with confidence that relapsing. NEDA is progressive MS. We have to see what early treatment with highly active treatment brings and no I would not including hhhighy effective treatment, it has to be early because even in the mice we know there is a point when it is too late,

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    4. Progressive MS There is nowan internationalconsortium tasks with cracking this nut.

      However, out the UK we have already seen positive results of phenytoin and positive data from simvastatin an even positive data from THC is you read between the lines,

      However the problem is that doctors can not develop drugs they do not have the resource. Pharma is spending too much time testing immunologicals that have a low chance of success.

      The system needs to be changed and you the people have to lobby for a change that can allow this to happen. If a trial of 600 people takes seven years to complete (2 years to recruit, 3 year trial, 1 year to analyse and another year to get approval) it is not going to be quick.

      Drug development takes a long time 10-15 years is a norm, that is the process. If you want to change this process then you have to lobby but this is there to ensure your safety.

      Genes are may give direct targets from the gene because no single gene is absolutely necessary however it gives you ideas of the proteins involved in the disease process.. Most genes have small influences. We have known about the main one for nearly fifty years. It tells us there is an immune issue. Interleukin 2 receptor gives you daclizumab activity the reason it was tried was not because of a genetic variant.

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    5. A lot of funding that did not come my way, £4,000,000 and maybe we can have change.
      I cannot try to justify how other peoples money but I again say the amount of money that MS gets is dwarfed by the research incomes of cancer research..

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    6. 5 most significant discoveries....I will keep my choices to myself.

      This is the domain of ProfG. He seems to like to put his head on the block for you to cut it off. Personally I can do without the abuse I get enough as it is thanks.

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    7. Awww MD, I feel you need a virtual hug to say some of us appreciate all your hard work. It must be so tough getting abuse nearly ever day just for having a different opinion to someone else (and I think -on the whole -you have the informed opinion) , especially when you are trying to help x

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    8. "By the way - I admire you guys and what you do here, and just the chance to communicate to a MS researcher is a privilege." you're very welcome.
      "Awww MD, I feel you need a virtual hug to say some of us appreciate all your hard work."
      Group hug virtual or actual everyone!! ;-)

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    9. p.s. Anon 1:55 I was not fishing for complements but if you put out your opinion and it all goes to pot, you open yourself up.

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    10. Blimey, I didn't think you were, I genuinely admire all your efforts with this blog. I've done blog moderation myself for political websites so I have some empathy about the utter crap you get thrown at you and what you mean by giving an opinion (inadvertently light the touchpaper and all hell can break loose, sometimes).

      I wonder if this blue full super moon today is affecting people. Not into astrology but maybe there is 'something' to the so called 'lunar affect';)

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  32. Did you guys see this a few days ago for masitinib in PPMS/SPMS? It says a 3rd of patients in the Phase III are now 1/2-way through it and their results are deemed 'non-futile'. I'm not really sure if that's something to celebrate, or not. Do most Phase IIIs for PPMS pass this test? Or are most even subjected to it in the first place?

    https://globenewswire.com/news-release/2015/07/23/754662/10142952/en/AB-Science-announces-successful-non-futility-test-for-masitinib-in-progressive-forms-of-multiple-sclerosis.html

    I get the gist of what they're saying, but I can't tell if it's just positive spin by the company, or something genuinely worth getting our hopes up for. What's your take Mouse Docs?

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    Replies
    1. Masitinib? Is that a mast cell thing? Not a monoclonal antibody, judging from the name.

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    2. It was a drug made against mast cell tumours it is a tyrosine kinase (a signalling molecule in a cell) that can affect cytokines like PDGF which is involed in oligodendrocyte development.

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    3. Non futility means they think it is worthwhile to complete. It could be that the placebo is worsening at a sufficiently fast rate to get an idea of whether the trial is worthwhile. In the CUPID trial the placebo arm did very much better than would be predicted. However it could be that it is an indication that the drug is working.As such the news announcement is made to increase the share price
      The data is looking at the results of a change in EDSS after less than one year, to get a significant effect in one year maybe good going.So be positive but do not let your hopes run away with themselves.

      BMC Neurol. 2012;12:36. doi: 10.1186/1471-2377-12-36.
      Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study.Vermersch P1, Benrabah R, Schmidt N, Zéphir H, Clavelou P, Vongsouthi C, Dubreuil P, Moussy A, Hermine O.

      BACKGROUND:
      Treatment options for patients suffering from progressive forms of multiple sclerosis (MS) remain inadequate. Mast cells actively participate in the pathogenesis of MS, in part because they release large amounts of various mediators that sustain the inflammatory network. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. This exploratory study assessed the safety and clinical benefit of masitinib in the treatment of primary progressive MS (PPMS) or relapse-free secondary progressive MS (rfSPMS).
      METHODS:
      Multicenter, randomized, placebo-controlled, proof-of-concept trial. Masitinib was administered orally at 3 to 6 mg/kg/day for at least 12 months, with dose adjustment permitted in event of insufficient response with no toxicity. The primary response endpoint was the change relative to baseline in the multiple sclerosis functional composite score (MSFC). Clinical response was defined as an increase in MSFC score relative to baseline of > 100%.
      RESULTS:
      Thirty-five patients were randomized to receive masitinib (N = 27) or placebo (N = 8). Masitinib was relatively well tolerated with the most common adverse events being asthenia, rash, nausea, edema, and diarrhea. The overall frequency of adverse events was similar to the placebo group, however, a higher incidence of severe and serious events was associated with masitinib treatment. Masitinib appeared to have a positive effect on MS-related impairment for PPMS and rfSPMS patients, as evidenced by an improvement in MSFC scores relative to baseline, compared with a worsening MSFC score in patients receiving placebo; +103% ± 189 versus -60% ± 190 at month-12, respectively. This positive, albeit non-statistically significant response was observed as early as month-3 and sustained through to month-18, with similar trends seen in the PPMS and rfSPMS subpopulations. A total of 7/22 (32%) assessable masitinib patients reported clinical response following 12 months of treatment (according to the modified intent-to-treat population, observed cases) compared with none in the placebo group. The Expanded Disability Status Scale remained stable for both treatment groups.
      CONCLUSION:
      These data suggest that masitinib is of therapeutic benefit to PPMS and rfSPMS patients and could therefore represent an innovative avenue of treatment for this disease. This exploratory trial provides evidence that may support a larger placebo-controlled investigation

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