@bsw5020 1/ Several independent points. 1. As a "PROGNOSTIC" biomarker, a single baseline measurement can predict rate of decline and survival probability at a given later time-point - enables more reliable detection a treatment effect with a smaller number of patients enrolled.
@bsw5020 2/ Serum to CSF neurofilament concentrations were strong, particularly for NfL on the Simoa platform - so can potentially use a blood test instead of spinal fluid.
@bsw5020 3/ To use a measurement as a "PHARMACODYNAMIC" biomarker of changes due to a treatment, you need to characterize their longitudinal trajectories. For example, if a measurement stays stable over time as disease progresses, perhaps an effective treatment will lower it. Or, if
@bsw5020 4/ a measurement increases over time, then perhaps an effective treatment will stop that increase. HOWEVER, it is impossible to know for certain if something can detect a "effective treatment" until we actually have an effective treatment. IMPORTANTLY, this study shows that...
@bsw5020 5/ while absolute values of serum NfL can vary between patients, the levels remain largely stable in a given patient over time. Therefore, it could be useful to detect a CHANGE in level with treatment. This is supported by published studies of Nusinersen for SMA - in which...
@bsw5020 6/ the stable NfL levels over time were decreased by the effective therapeutic. However, definitive proof of PHARMACODYNAMIC biomarker utility requires an effective treatement to test.
3rd point - while there have been LOTS of studies on neurofilaments in ALS, to be truly...
3rd point - while there have been LOTS of studies on neurofilaments in ALS, to be truly...
@bsw5020 7/ useful in clinical trials, we need to rigorously understand the performance of ALL of the commercially available assays, as well as how their performance may vary in different labs. For this study, the highly curated
@CReATeRDCRN samples were sent blinded to different CROs..
@CReATeRDCRN samples were sent blinded to different CROs..
@bsw5020 @CReATeRDCRN 8/ Running different commercial assays, so that the performance on the SAME sample sets can be compared across assays, and in different laboratories - critical info to make a test "clinical trial ready." All of the raw data from all the CROs, and associated deidentified...
@bsw5020 @CReATeRDCRN 9/ clinical data are being broadly and openly available via Dryad at doi.org/10.5061/dryad.…. The link hasn't gone live yet, but I believe it should right away. /END
@bsw5020 @CReATeRDCRN 10/ (please excuse any typos in this thread - hopefully made sense!) Would not have been possible without collaborative support from several foundations & the #NIH, and the work of numerous teams at many academic centers. @CReATeRDCRN @TargetALS_fdn @alsassociation @MDAorg
