Validating biomarkers for effective drug development

10-Dec-2019 08:00

Fluid-based biomarkers may potentially address these issues.

An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients.

Recent longitudinal studies examining p NFH in CSF or blood show relatively stable levels over time, though levels of p NFH in serum appeared to increase at early stages of the disease []. measured levels of p NFH and NFL in CSF and blood of symptomatic and asymptomatic carriers of disease causing mutations to determine if either biomarker could be detected in symptomatic individuals [].

While elevated levels were observed in symptomatic mutation carriers, neither p NFH nor NFL were detected at elevated levels in asymptomatic ALS mutation carriers.

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However, the majority of studies have been performed on CSF, serum, and plasma.

It should be noted that one caveat of this study is that most of the asymptomatic mutation carriers harbored the does not have 100% penetrance and therefore some of these individuals may never develop ALS and thus no changes in p NFH or NFL would be detected, which is consistent with the results from this study.

A study in the superoxide dismutase 1 (SOD1) transgenic mouse model of ALS also indicated that p NFH levels increase near or at the time of symptom onset.

Accumulation of neurofilament proteins has been linked to MN dysfunction [].

Axonal injury releases these proteins into the CSF and subsequently to the blood.

However, the majority of studies have been performed on CSF, serum, and plasma.It should be noted that one caveat of this study is that most of the asymptomatic mutation carriers harbored the does not have 100% penetrance and therefore some of these individuals may never develop ALS and thus no changes in p NFH or NFL would be detected, which is consistent with the results from this study.A study in the superoxide dismutase 1 (SOD1) transgenic mouse model of ALS also indicated that p NFH levels increase near or at the time of symptom onset.Accumulation of neurofilament proteins has been linked to MN dysfunction [].Axonal injury releases these proteins into the CSF and subsequently to the blood.As the disease progresses, patients exhibit muscle atrophy and consequently lose respiratory function.