I found this article interesting regarding NfL...

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Havenots

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19/08/23

06:42

Post #: 69429830
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Originally posted by kpax: ↑

Hi all,

In the past 10 years, considerable progress has been made in the characterization of neurofilament light chain (NFL) as cerebrospinal fluid (CSF) and blood biomarker for both diseases. NFL is a structural component of the axonal cytoskeleton and is released into the CSF as a consequence of axonal damage or degeneration, thus behaving in general as a relatively non-specific marker of neuroaxonal pathology.

However, in ALS, the elevation of its CSF levels exceeds that observed in most other neurological diseases, making it useful for the discrimination from mimic conditions and potentially worthy of consideration for introduction into diagnostic criteria. Moreover, NFL correlates with disease progression rate and is negatively associated with survival, thus providing prognostic information. In frontotemporal dementia FTD patients, CSF NFL is elevated compared with healthy individuals and, to a lesser extent, patients with other forms of dementia, but the latter difference is not sufficient to enable a satisfying diagnostic performance at individual patient level

However, also in FTD, CSF NFL correlates with several measures of disease severity. Due to technological progress, NFL can now be quantified also in peripheral blood, where it is present at much lower concentrations compared with CSF, thus allowing less invasive sampling, scalability, and longitudinal measurements

The latter has promoted innovative studies demonstrating longitudinal kinetics of NFL in presymptomatic individuals harboring gene mutations causing ALS and FTD. Especially in ALS, NFL levels are generally stable over time, which, together with their correlation with progression rate, makes NFL an ideal pharmacodynamic biomarker for therapeutic trials.

Reference: Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia 2021

To me this NFL biomarker V MPL administration results are pivotal for success in the treatment of MND. I can't wait to cross compare our treatment versus current drug regime to quantify and see where we sit on efficacy in this biomarker. Then we can get on with the efficiency of scale. In other words get it out there!

Have a good weekend, we are nigh on the cusp of something very tangible. If you crack a bottle of champagne over the the next 72 hours or that prized bottle of Scotch I thoroughly understand.

Kpax

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I found this article interesting regarding NfL testing.

https://academic.oup.com/brain/article/146/7/2711/6780887?login=false

In particular this paragraph:

My interpretation is that for NfL testing to be an effective predictor the test should, preferably, be done during the stable areas. Most trial subjects will have a different trial commencement NfL level, therefore the relative size of their reduction could indicate greater survival time.

@kpax could it be possible that the trial participant, that did not have a reduction in either of the bio-markers in previous bio marker results, may be too early in his/her disease progression? (Probably highly unlikely as it would have, no doubt, been considered by trial PI)

Regards,

Not long now (finally feels like this statement is actually true, versus the hope I have had when I said it in the past)

Havelots

Last edited by Havenots: 19/08/23

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18 Upvote

7 Great analysis

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