Metabolic Alteration and Amyotrophic Lateral Sclerosis Outcome: A Systematic Review

Abstract

Background: The development of strategies that could not only efficiently detect the onset of Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder with no cure but also predict its development and evaluate therapeutic intervention would be of great value. In this respect, the metabolic status of ALS patients has called attention. Hence, this study aimed to investigate the potential correlation between changes in ALS's metabolic parameters with the disease outcome in a systematic review.Methods: The manuscripts were manually searched within different databases (PubMed, Web of Science and Cochrane). The inclusion criteria were original articles and reviews about individuals with ALS and its survival, disease prognosis and metabolism (weight, cholesterol, hypertension, BMI, and glycaemia). The authors also established three different exclusion criteria: studies including ALS and other degenerative disorders, works including animal models and published before the year 2000.Results: In total, 29 papers were selected. From all manuscripts, only 82.8% ensured the participation of sALS patients. Also, 27.6% of selected studies described the presence of a genetic mutation. Regarding ALS prognosis, patient's age, the age of ALS onset, ALS duration and survival, <50% of the papers addressed these issues. Specifically, regarding metabolism, 65.5% of articles mentioned BMI, 20.7% mentioned any data concerning hypertension, 6.89% cardiovascular risk, 10.3% obesity, 13.78% diabetes and 10.3% glycaemia. Concerning lipid metabolism, more results were gathered, but still, they did not suffice to establish a correlation with ALS development.Conclusions: Altogether, the authors concluded that available information is not enough to establish a link between ALS and metabolism. In reality, less than half of the manuscripts evaluated show an association between both factors. Nonetheless, it is worth mentioning that metabolism does influence ALS, but not in a unique manner. There is a debate about patients' hypo- and hypermetabolism. Thus, to provide a reliable record, a public policy in which all research and clinical centers might assess the parameters discussed herein is suggested. Accordingly, this systematic review attempts to provide a comprehensible database to facilitate multicentered collaboration, validation, and clinical translation.

Decreased Mitochondrial Function, Biogenesis, and Degradation in Peripheral Blood Mononuclear Cells from Amyotrophic Lateral Sclerosis Patients as a Potential Tool for Biomarker Research

“…Importantly, all individuals evaluated were Caucasian. As mentioned previously [ 9 ], we believe that ethnicity is crucial to the interpretation of results, since metabolism can be modulated, at least partially, by polymorphisms that might be ethnically dependent [ 9 ].…”

“…To date, the most common medication used by ALS patients is Rilutek TM (riluzole) [ 189 – 191 ], known as a wide-spectrum medication [ 9 , 39 , 192 – 195 ] and showing different effects in later stages of the disease [ 192 , 196 ]. Therefore, one might think that the data presented would point toward the effect of riluzole.…”

“…Moreover, the lack of knowledge regarding secondary mechanisms related to the disease progression represents a struggle for the academic community, especially because diagnosis and prognosis are mainly based on physical exams [ 23 ]. Unfortunately, this is a matter of debate that affects all studies performed with ALS patients [ 9 ].…”

“…Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by a specific and progressive degeneration of upper and lower motor neurons followed by muscular atrophy [ 1 – 9 ]. Although several pathological mechanisms have been postulated to explain ALS genesis and progression, this matter is still under debate and goes beyond genetic alterations; mutations (~ 24 genes) account for 68% of familial cases of ALS (fALS) and for just 11% of sporadic ALS (sALS) [ 10 ].…”

Mitochondrial Dysfunction, Neurogenesis, and Epigenetics: Putative Implications for Amyotrophic Lateral Sclerosis Neurodegeneration and Treatment

“…Unfortunately, there is currently no effective treatment or cure for this devastating neurodegenerative disease, albeit some medications used to attenuate symptoms ( Brito et al, 2019 ), such as Rilutek TM (riluzole) and Radicava TM (edaravone) ( Martin et al, 1993 ; Sawada, 2017 ; Brito et al, 2019 ). On the other hand, to extend their life expectancy, ALS patients undergo tracheostomy-delivered assisted ventilation ( Hayashi and Kato, 1989 ; Jimenez-Pacheco et al, 2017 ).…”