ALS and C-Reactive Protein
C-reactive protein (CRP) is a well-recognized biological marker of the overall degree of systemic inflammation. ALS researchers have hypothesized that the rate of ALS progression is correlated with CRP blood levels. CRP is easily measured with either a wide-range CRP (wr-CRP) or high sensitivity CRP (hs-CRP) assay. Published data in the journal Acta Neurologica Scandinavica [i] [Figure 1], indicate that ALS patients with higher levels of CRP tend to progress faster.
The same correlation was observed in Neuraltus’ Phase 2 study in which patients receiving a placebo dose progressed faster if their baseline CRP level was greater than the median for all patients in the study [Figure 2].
Elevated levels of CRP are reflective of an increased inflammatory macrophage state. There are also data from other disorders indicating that CRP may promote differentiation of monocytes to an inflammatory state. Inflammatory macrophages contribute to neuronal damage and neuronal cell death in the central nervous system, and thereby lead to ALS progression.
In 2017, results from an independent retrospective analysis of three clinical data sets in ALS, including NP001 Phase 2 data, were published in the online edition of JAMA Neurology [ii]. The analysis found a correlation between serum CRP levels and the rate of disease progression of ALS in two large cohorts of Italian patients, and reinforced the use of CRP as a biomarker and potential indicator of disease progression in individuals with ALS [Figure 3][ii].
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[i] Acta Neurol Scand. 2009 Jun;119(6):383-9. doi: 10.1111/j.1600-0404.2008.01112.x. Epub 2008 Oct 23. http://www.ncbi.nlm.nih.gov/ Last Accessed February 2016.
[ii] JAMA Neurol. 2017 Apr 3. doi: 10.1001/jamaneurol.2016.6179. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/ Last Accessed May 2017.