Wednesday, 21 October 2009

Panel recommends that FDA approves Fampridine for increasing walking speed in PwMS


Concerns:

Aminopyridines, a family of compounds to which Fampridine belongs, works by lowering the requirements for axons (the electrical cabling of nerves) by blocking a specific group of proteins on their surface called voltage-gated potassium channels. This makes it more likely for an electrical impulse or action potential to be transmitted across a demyelinated segment of an axon. Although this will improve motor function the effect on sensory and other pathways may make some problems worse, for example exacerbation of pain and increase in the frequency and severity of MS-related positive symptoms (pins & needles, muscle spasms and seizures).
Aminopyridines will almost certainly increase the energy requirements of damaged, vulnerable, demyelinated axons as they will require more energy for repolarization the process by which they get ready to transmit another electrical signal. There is now good evidence that increasing the energy requirements of axons may result in further axonal injury and loss. Essentially this is the theory underlying the use of sodium channel blockers, such as phenytoin or lamotrigine, as neuroprotective compounds in MS; by reducing transmission you reduce the energy requirements and hence protect vulnerable axons.
For these reasons I am wary about the long-term use of Fampridine in MS-related motor fatigue. I am worried that Fampridine may speed up the rate of disability progression. I stand to be proved incorrect on this; we will only find this out by doing clinical trials and following up patients with progressive MS on these medications for long periods of time using standardised methods.
I have posted Hugh Bostock’s videos, from Queen Square, on conduction in a normal nerve and a demyelinated nerve, on YouTube, to illustrate how slow and difficult it is to transmit an electrical impulse down a demyelinated nerve. When you watch the videos please try and imagine how much more effort/energy is required for conduction in demyelinated axons; aminopyridines are the chemical whips that keeps these axons firing.

Prof G

8 comments:

  1. I think people also forget that K+ channels are not only expressed on axons but also astrocytes, the cell type primarily responsible for glutamate uptake. Hypothetically Fampiridine can affect glial cell mediated potassium/glutamate homeostasis ---> reduced clearance of extracellular glutamate!! Hey presto, inc neuronal excitability and seizures!!!



    But I suspect, homeostasis will re-establish itself pretty quickly as with all channel blockers.

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  2. I would agree that any short-term gain will be, probably quite rapidly, countered by long-term increase in disablity due to numerous energy-deficient axons giving up the ghost. Could have some cognitive consequences too.

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  3. I must say that neurologists and consultants have a very skewed approach to progressive forms of MS. Something like primary progressive is not only incurable, it is untreatable. What say you to the thousands of British sufferers who have lived without hope for countless decades and now have had another promising treatment implode before their eyes? Neuroregeneration is merely a theory right now whereas Fampradine is an actuality.

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  4. As a carer and having no idea about the terms used,(it may sound good to those trained but to the public who seek advice ..........), does this drug have any benefits at all from results obtained from countries where it has been used since issue and do they show side effects as well.

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  5. Something like primary progressive is not only incurable, it is untreatable.

    I think it is treatable, we just need to get drugs available to progressive MSers

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  6. Prof G will no doubt say more.

    Does this drug have benefits....

    If you look through the blog you can see there are benefits that some people have with fampridine it appears remarkable but there are many MSers you appear to gain no benefit form this treatment.

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  7. I have been taking fampridine for the last three months and I can realistically say that this medication has been beneficial to myself with PPMS.

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  8. disability progression is an interesting subject in itself-no one can predict the future other than retrospectively looking backwards to see how one was sometime ago and balancing this with the present. What fampridine seems to be able to do, is to restore slightly ones mobility and degree of confidence. Other issues are improved, including cognition speech easing spasticity and aiding symmetry in my posture. Whereas before weakness was more apparent on my left side. This medication does help and it's preferable to the agents already available for neuropathic pain. This obviously is from a personal perspective.

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