Creatine Kinase and Progression Rate in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no recognized clinical prognostic factor. Creatinine kinase (CK) increase in these patients is already described with conflicting results on prognosis and survival. In 126 ALS patients who were fast or slow disease progressors, CK levels were assayed for 16 months every 4 months in an observational case-control cohort study with prospective data collection conducted in Italy. CK was also measured at baseline in 88 CIDP patients with secondary axonal damage and in two mouse strains (129SvHSD and C57-BL) carrying the same SOD1G93A transgene expression but showing a fast (129Sv-SOD1G93A) and slow (C57-SOD1G93A) ALS progression rate. Higher CK was found in ALS slow progressors compared to fast progressors in T1, T2, T3, and T4, with a correlation with Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores. Higher CK was found in spinal compared to bulbar-onset patients. Transgenic and non-transgenic C57BL mice showed higher CK levels compared to 129SvHSD strain. At baseline mean CK was higher in ALS compared to CIDP. CK can predict the disease progression, with slow progressors associated with higher levels and fast progressors to lower levels, in both ALS patients and mice. CK is higher in ALS patients compared to patients with CIDP with secondary axonal damage; the higher levels of CK in slow progressors patients, but also in C57BL transgenic and non-transgenic mice designs CK as a predisposing factor for disease rate progression.

A longitudinal study defined circulating microRNAs as reliable biomarkers for disease prognosis and progression in ALS human patients

“…As reported in Fig. 5a, the CPK levels decrease in both fast and slow progressing patients in line with previous evidence 21,22 , and the linear regression analysis highlighted a significant difference in the slope of the CPK linear curve. In particular, the slope or rate decline of the slow progressing patients resulted significantly smaller compared with the fast progressing ones (p ≤ 0.001).…”

Analysis of routine blood parameters in patients with amyotrophic lateral sclerosis and evaluation of a possible correlation with disease progression—a multicenter study

“…Since CK is an enzyme involved in the muscle's energy metabolism (19), some researchers also assumed that upregulation improves muscle energy and function. This is supported by the finding that patients with higher CK levels tend to show slower progression (20,33) and that CK declines faster in rapidly progressive disease (50). We found an association between rate of decay and CK levels in the linear univariate model, but the result was not reproducible in the multivariate model including basic variables.…”

Swim training affects Akt signaling and ameliorates loss of skeletal muscle mass in a mouse model of amyotrophic lateral sclerosis

“…There is also evidence of elevated serum CK levels in the early stage of sALS 36 . Changes in the blood CK activities in patients with ALS were recently presented in a new perspective, with higher CK levels reported for an ALS model with a slowly progressing disease than in an ALS model with a fast-progressing disease 37 . The study suggested that the slow-progressing mice progress slower because they have greater muscle mass and may counter disease mechanisms for more extended periods than the fast-progressing mice 37 .…”