Friday, 20 September 2013

Imaging spasticity

Are you a baclofen zombie? #MSBlog #MSResearch

"This study simply shows that MSers are more likely to have spasticity if they have MRI lesions loads and if those lesions are in a pathway that affects the nerve fibres that control motor function. This is what we expect. However, it stresses the link between the number of MRI lesions, or burden of disease, and spasticity. The corollary of  this is if can prevent these lesions from forming the first place you will prevent the damage to the motor pathway and spasticity developing."
"Spasticity is when any passive fast movement of the leg is resisted by the muscles contracting. If severe spasticity can cause spasms and limb jerks. This is a particular problem at night when you are asleep; limb jerks tend to keep you awake at night. When spasticity is bad it often associated with pain and discomfort in the muscles. Spasticity is made worse by pressure and ill fitting orthotics and shoes; please check to make sure this is not a problem. In addition, spasticity typically gets worse with infections and when you are tired."

Are you a baclofen zombie?

"We have many drugs for treating spasticity, all of them cause sedation and can make cognitive impairment worse. Baclofen the most commonly prescribed anti-spastic agent has a short half-life (time it takes for the concentration in the blood to halve itself) and hence wears off too quickly. This is why you need to take it 3 or 4 times a day and in some circumstance more often. Because of the problems with baclofen, and other antispastic agents, MouseDoctor 1 & 2, have been working hard to address this unmet need. They have discovered a class of agents that works in the periphery and does not cause sedation in our animal model of MS. To commercialise these compounds they have formed a University spin-off company called Canbex. The first-in-man or phase 1 studies are about to start. So please watch this space if you are interested to see if this gets through the pipeline."

"Is the Canbex business model flawed? If we treat MS early and actively with highly-effective therapies and prevent or delay secondary progressive MS we may reduce the market for Canbex's products substantially. Do you think they we have a conflict of interest?"

Bertoni et al. Neuroimaging assessment of spasticity developed after acquired brain injuries and multiple sclerosis. Neuroradiol J. 2012;25(3):311-7. 

Background: This study evaluated whether different imaging techniques correlate with specific variables routinely used to grade the types and complexities of people with conditions in neurorehabilitation services and their clinical outcomes, and if there are radiological patterns, topography or distribution of the lesions correlated to spasticity. 

Subjects & Methods: The cohort studied included 75 patients, 38 MSers and 37 patients with acquired brain injuries (ABI) referred to the neurorehabilitation department from April 2009 to March 2010. Data included age, gender, diagnoses, complications, spasticity, length of stay, Rehabilitation Complexity Scale (RCS) and Northwick Park Dependency (NPDS) scores on admission and discharge. Forward stepwise multiple regressions were performed considering Spasticity as dependent and considering NPDS, RCS on admission and discharge, age, gender and length of stay as independent variables. Standardized intra-axial lesions in those with spasticity were fused with standardized axial DTIs from normal controls obtained under 3 T and 1.5 T MRI scanners.

Results: Spasticity was present in 36 patients. Regression was found between spasticity and all the other variables with r = 0.42, r(2) = 0.17, p < 0.01. Residuals were acceptable. If the same is calculated excluding MS patients the results are higher with: r = 0.59, r(2) = 0.35, p < 0.003. In MS subjects, spasticity appeared if lesions affected pyramidal tracts, callosal radiations extensively or brainstem. 

Conclusions: Findings suggest that NPDSa and discharge and RCSd are higher in those developing spasticity. No obvious correlation between spasticity and RCSa was found. Subjects with MS are more likely to develop spasticity especially if the lesions are numerous and affect the corticospinal tracts, callosal radiations extensively or brainstem. In patients with ABI lesions affecting pyramidal tracts, pericommissural areas and optochiasmatic cisterns seem more likely to develop spasticity.

To read more about Canbex:

25 Apr 2013
Canbex Therapeutics Ltd has completed a £2.1m ($3.2m) fundraising round that will enable the Company to complete the early development of its lead candidate for the treatment of spasticity in multiple sclerosis (MS).

25 comments:

  1. My gut feeling is that there will still be a large market for any such drug, so no COI.

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  2. As long as the first line treatments are not 100% effective there will be place for symptomatic treatment. And I wouldn't be worried: the effect of no such drug can be even compared to the healthy nervous system. The ability of people (and brains) to accommodate neurological disability is tremendous. Drugs like Baclofen and other symptomatic drugs are there to provide some relief from the un-accommodatable tip of the iceberg.

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  3. I think MD1 & MD2 should donate all the money they make from Canbex to an MS Charity.

    ReplyDelete
    Replies
    1. MD1 & MD2 have done a lot of work for Canbex in their own personal time; i.e. not as part of their day jobs. I don't see why they should have to donate any money, that's if Canbex makes any money, to charity simply because they have another source of income? Our current work contracts allow us to allocate 10% of our time to consultancy work; Canbex is their consultancy work.

      I am not sure if you are aware what academic scientists are paid in the UK? Not enough in my opinion. I would encourage them to keep the money and to only make a donation to charity if that is what they wanted to do and not because someone else insisted they do so.

      Do you think the venture capitalists who have invested in Canbex will be donating their profits to charity? MD1 & MD2 have invested hundreds, if not thousands, of hours in the science that underpins Canbex. Why should their time be treated differently to Venture capital?

      Delete
    2. I agree with anon above. What would MD1 do with sacks of cash from discovering a new drug? Beer, heavy metal CDs, dodgy waistcoats etc.

      Medicine / medical research is a calling - you should all be doing it for the right reasons - to help your fellow men / women. The lure of earning money outside your day job undermines the integrity of your professions.

      Delete
    3. Tell all this to the thousands of fundraisers and people working in the Charity shops for free.

      Delete
    4. So MD2 is getting a really good deal in all of this

      Time invested. On and off so far 11 years
      Published papers so far = 0
      Money received = £0.00
      Inventor shares = diluted substantially by Venture capitalists and can only get more diluted.

      I am not much better off...I have 1 paper to show for 11 years....second on the way soon

      Delete
    5. Medical research is a calling it is trying to help your fellow men/ women....Drugs do not grow on trees someone has to invent and develop them this a central part of medical research.

      If you think pharma invent all drugs.....think again because you are dreaming.

      Delete
    6. Prof G as a consultant neuro will be on at least 130k. Mouse D as a Professor must be approaching 100k. The average wage in this country is c.28K. You guys needs appreciate how well off you are. All this "I'm a poor academic stuff" is a bit of a joke. Why do you need more money from all the consultancy work / potential money from creating a new drug? Do your main job well and focus on it. All this extra-work will make you tired and you'll be less effective at your normal job. I wouldn't mind you guys making all this dosh if you made people with MS better. I don't see this as yet. Give us what we need / want and you'll be richly rewarded in heaven. Making all this money (as does pharma) from this "dementing disease" sucks. If you had MS and lost your job, you'd know what hard up meant!

      Delete
    7. Dear Anon A5:42:00 am

      Do you have any idea how better off people with MS are today, compared to say 20 years ago? It is because people like Mouse D and Prof G work in the field. I don't begrudge them anything they earn. I suspect they are like most academics not in it for the money.

      Delete
  4. I think the conflict of interest is obvious. Their academic job aims to prevent/cure/reduce MS, while Canbex's success depends on people being sick.

    I'm not condemning/criticising them for pursuing this business, they deserve to make money from their work like anyone else. But it will definitely make me question the interests behind their opinions from now on.

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    Replies
    1. Conflict of interest......Groan...Please get real.

      As employees our employers take the lions share of an invention. They are the people who want academic entrepreneurs and take an increasing cut if there is any money to be made....So far this is zero

      If you are willing to buy the company and take on the development to market please contact the chair and CEO...It will free up my time to do something more lucrative....at present it has cost me at least seven figure sums.

      Delete
    2. MouseDoctor have we hit a nerve? Why so defensive? Millions of people in this country work for employers and companies for long hours. They do not receive anything more than their salaries when the business makes a profit. How many people in the public sector get money for doing their job? Anon 7:13 was only saying he or she will take the conflicts into account when reading this blog. I can't see anything wrong with the that.

      Delete
    3. Please read the conflicts of interstsection that has been on the front page.

      Touch a nerve no not at all.

      After. my fourteen hour day i will be home in 5 min for beer o'clock. Then onto computer to get that paper submitted.

      Delete
  5. "MD1 & MD2 have done a lot of work for Canbex in their own personal time; i.e. not as part of their day jobs."

    So you're saying they worked on Canbex without any of the resources of the laboratories the work at durring their day job? The must have a mouse lab in their garage. Where I work anything that is invented that was developed with company resources is the companies. Things must be different in the UK.

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    Replies
    1. Of course the basic idea and work were done in our day job that is why
      the universities have the lions share.

      However once you get beyond the original idea and proof of concept it is not necessarily about labwork but about co-ordinating the necessary experiments and organising the funding and then you use contract testing facilities etc for the many things that the regulators need

      Delete
    2. P.S. The universities may also get paid for the contract work,so they charge the company the market rate for our expertise.

      Delete
  6. I fully support MD in his efforts. He absolutely should be able to work in his free time to do whatever he pleases, and I applaud you for your ambition. I wish you best of luck MD in your new company and hope you are successful in all you do. Thanks for working to better the lives of us MSers.

    To all you anonymous commenters: You should spend more time thinking about how you spend your free time and money and stop trying to tell what others what to do.

    ReplyDelete
    Replies
    1. I am sure I can speak for MD2 and the other academic partners they are not in it for the money and we expect to see little if any,but there is a desire to deliver a useful treatment option.

      How do you teach about translational neuroscience without understanding the process and there is a process.

      We are getting to the stage where we have a 90% chance of failing not bad considering we started with a 99.99% chance of failure

      Delete
    2. Sorry MD, didn't mean to insinuate that you were in it just for the money. I believe you are trying your best to help MSers, and we appreciate it. Money isn't the goal, it is just a way of keeping score.

      It dismays and surprises me the number of negative responses to this post. A potential new treatment for spasticity is being developed, and all people can think about to post is you should accept no money? What is next-- you shouldn't be working in your spare time because it isn't in your paid contract? We need more optimism in the world, and the ambition to go the extra mile to achieve a goal. Not with you researchers, but the attitudes of people in general.

      As always, we appreciate this blog and all your hard work!

      Delete
    3. It dismays and surprises me the number of negative responses to this post.


      Just look at the comments after the announcement of EMA approval of Lemtrada.

      As to 100K.....in my dreams

      Delete
  7. The trouble is, the money that is made from these mew drugs and treatments is paid for by the taxpayer via the cash strapped NHS. The recent problems in the health service are mainly due to cost cutting. This is not an attack on Prof G or the Mousedoctors, it is the system. It is important to know all the facts when any doctor recommends a treatment, in case there is a conflict of interest.

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  8. I wish you the best with your venture. However, I understand the sour grapes. I was an entrepreneur. Now not. Between cognitive issues and MS fatigue I am fortunate to still work at all as a fairly low level employee. Any hopes I had in that realm, job satisfaction, professional recognition or cash reward are gone.

    None of the anger is personal to you. Good luck. I hope your product helps many and makes money. Better you than the established giant corps.

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  9. Really, what's all the fuzz about. The first in line tests are about to start... As far as I know we are still years and years from a real medicine.. so why all this MD bashing...? Let's at least wait until there is something worthwile to talk about. If they have the stamnia to pursue this to the end then they are certinally worth some kind or reward. As for me I cannot wait to get something that can ease my pain without the side effects the meds have that I use today.
    So good on you MDs.
    //Swedish Sara

    ReplyDelete

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