Atypical Levels of Heavy Metals, Creatinine, Haptoglobin, and Ferritin Found in Amyotrophic Lateral Sclerosis Outpatients vs. Healthy Controls: Possible Utility as a Diagnostic Biomarker

Abstract

Heavy metal toxicity has been conjectured as a possible risk factor for and player in amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. To test for a correlational relationship or linkage, we conducted a retrospective study of 54 sALS and 26 healthy volunteers who agreed to serve as controls, all of whom were seen at the Personalized Regenerative Medicine Clinic (San Clemente, California USA) between 2011 and 2016. We evaluated clinical laboratory findings including heavy metal content in blood and urine samples, along with serum creatinine, ferritin and haptoglobin levels, by means of inductively coupled plasma optical spectrometry and instrumental activation analysis. Disease progression, assessed using the Revised ALS Functional Rating Scale (ALS-FRS-R), was generally associated with mercury, lead, cadmium, arsenic and nickel burden. In our analysis, we found evidence of an association between ALS morbidity risk and elevated levels of mercury, lead, cadmium, arsenic, and nickel. Our findings implicate and support a linkage between relatively high levels of heavy metals, elevated serum ferritin and haptoglobin levels, and reduced urine creatinine level and sporadic amyotrophic lateral sclerosis. By virtue of this the authors argue that these may serve as a biomarker to help distinguish clinically ALS from other, symptom similar neurogenerative conditions.

Stress response markers in the blood of São Tomé green sea turtles (Chelonia mydas) and their relation with accumulated metal levels

“…For that reason, values of ferritin transcription in the blood of these turtles may not be of great biomarker value, as their cause is very multifactorial. Nonetheless, it does support the indications that fer has also a role in the process of non-iron metals transport and detoxification (Chiou & Connor, 2018;Steenblock & Ikrar, 2019). In particular, 17.38% of fer explicable variance is negatively associated with Hg x Fe, meaning that the presence of increased values of both of those metals might decrease fer expression, while an over expression of this gene seems to occur in the presence of Hg x Se and Cd x Zn (positive associations with minor relative importance).…”

Proteomic analysis of human serum Extracellular Vesicles reveals early diagnostic markers for Amyotrophic Lateral Sclerosis

“…Given immune response was a biological process identified in the GO analysis, our study further supports haptoglobin's immunomodulatory role in the early stages of ALS. Finally, serum haptoglobin levels were discovered to positively correlate with sporadic ALS, disease stage, and be predictive of progression rate (Steenblock and Ikrar, 2019). Therefore, the upregulation of haptoglobin in ALS serum EVs elucidates dysregulation that may be occurring in the disease prior to treatment.…”

“…Protein biomarkers such as cytokines have had varying success whilst neurofilament heavy and light chains are more effective at monitoring disease progression than diagnosis (Gendron et al, 2017;Moreno-Martinez et al, 2019;Verde et al, 2019). Recently, haptoglobin has shown promise as an early biomarker for ALS, with its early elevation correlating with disease progression and severity (Steenblock and Ikrar, 2019). Despite advancements in the biomarker field, their stability in the bloodstream is still of concern.…”