Systemic Inflammation

ALS and C-Reactive Protein

C-reactive protein (CRP) is a recognized biological marker of the overall degree of systemic inflammation.  ALS researchers have hypothesized that the rate of ALS progression is correlated with CRP 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  Published data in the journal Acta Neurologica Scandinavica [i] [Figure 1], and unpublished findings by Stanley H. Appel, MD, indicate that ALS patients with higher levels of CRP tend to progress faster.  

Figure 1

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].

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.

NP001 and Macrophages

NP001 converts pro-inflammatory (activated) macrophages, a type of white blood cell, to their anti-inflammatory state.  The active ingredient in NP001, purified chlorite, combines with taurine in the macrophage to change the inflammatory macrophage back to its normal state [Figure 3]. NP001 is an investigational therapy and the only highly purified, intravenous formulation of sodium chlorite.


Figure 3

[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