As the New Year dawns, a look back @ Barts neurofilament service

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Back in 2015 there was a great need to prognosticate in MS, predict high risk subjects from low risk, and select appropriate treatments based on disease activity in MS.

We envisaged back then that the neurofilament test (a neuronal protein that is released during damage) would be a robust marker for risk-stratification in MS, and introduced into our clinical practice at Barts, instead of it being the holy grail of research studies only.

Wind forward 5 years and the test now forms an integral part of our MS multi-disciplinary team decision making processes, and importantly allows us to treat those who would not normally have been eligible based simply on popular thinking.

We are firm believers of following the science, and the test was intuitive and made logical sense. The growing popularity of the test across the UK and abroad attests to others thinking in a similar way (below are the quarterly figures for the Barts neurofilament test).

Figure provided by Dr David Holden (NFL service manager), tests performed by Dr Lucia Bianchi (post doctoral scientist in BartsMS)

‘For last year’s words belong to last years language’, and yet to drive this message forward myself and Prof Mark Freedman (University of Ottawa) are bringing together leading scientists and clinicians in neurofilament research to formulate a consensus in the applicability of the test and its function the across the world over at ACTRIMS-ECTRIMS 2020 meeting, Toronto.

If your centers are not currently offering this test they would all soon be. That is progress.

Happy New Year everyone!

About the author

Neuro Doc Gnanapavan

11 comments

    • Thanks Luis, this was also work done by our team. Neurofilament heavy chain is still in research but there is evidence from this and other progressive studies that it may be more informative.

  • Thoughts on WVE-120102 for Huntington’s disease trial results released today? Both the intrathecal administration and lack NFL response to small mutant htt reduction made me wish for the Bartish/Bartly/bartled reaction. To tie more closely to this post, is NFL typically slow to respond? When is optimal time to test after treatment? Are there any NFL mimics or lookalikes?

    • That’s interesting as NFL is found to be elevated in HD. They should test NFH also. I suspect there may be a lag and also the study in terms of numbers is not big in a phase 1b/2a study. I wouldn’t write it off entirely.

  • NDG,

    Thanks for this post.

    What is neurofilament testing measuring? Prof G now refers to smouldering MS as the real MS and the driver of progression, so is neurofilament testing measuring the damage caused by smouldering MS?

    Prof G also thinks that relapses and focal inflammation are not MS but the response to the real disease. Is there any point measuring the damage caused by relapses and focal inflammation is this is not the real disease?

    I suppose what my question is really about is can neurofilament testing differentiate between the nerve damage caused by smouldering MS (perhaps a response to the cause of MS eg a virus) and the nerve damage caused by relapses and focal inflammation?

    • Hi F, smouldering MS and inflammatory MS resulting in relapses are components of the same inflammation. There is a threshold needed for the inflammatory activity to be clinically evident and for lesions to be visible on MRI. The smouldering MS is ongoing inflammation that may not be evident in the scans but the person seems to be worsening. Neurofilaments don’t differentiate one from the other as it is an indicator of axonal injury from the inflammation. It can be located in both scenarios. So you can have elevated levels despite no changes visible on the scans. The latter is what I refer to when I refer to those not eligible for treatment may become eligible.
      I hope that makes some sense!

      • Thanks NDF.

        I’m having trouble getting my head around so called smouldering MS ie is it there to address an issue in the nerve cells and then the immune system gets involved (leading to focal relapses and focal inflammation) or does the immune system getting involved leave the slow burn (smouldering MS) behind.

        Happy 2020. I’m hoping for some advances in relation to unpicking the inflammatory components of MS. My Lemtrada treatment 10 years ago appears to have addressed relapses / focal inflammation, but the idea that there might be some slow burn inflammation still ongoing niggles me. My MRIs come back clean, but I’ve never been offered nfl testing.

        • Hi F, the short answer to both paradigms you mention there is that we don’t know yet. I suspect MRI will not be able to capture what we observe as continued immune activation – such may only be visible with biological sampling. For instance, in progressive MS where Dr K gave sun cut Cladribine (anti-inflammatory) there was prior to treating elevated NFL that later reduced after treatment.

          When you put your finger into something you need to have a reason, the same applies for neurofilament testing. You require a go/no-go option with the test result.

          Happy 2020 🙂

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