The hypometabolic state: a good predictor of a better prognosis in amyotrophic lateral sclerosis

Cattaneo, Marina; Jésus, Pierre; Fayemendy, P.; Guanziroli, Nicoletta; Corradi, Ettore; Sansone, Valeria; Leocani, Letizia; Filippi, Massimo; Riva, Nilo; Corcia, Philippe; Couratier, Philippe; Lunetta, Christian

doi:10.1136/jnnp-2021-326184

Cited by 15 publications

(15 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the epidemiological characteristics of ALS in Chinese are different from those in other countries. The mean age of onset in our study is 49.49 years old (SD 11.16), younger than patients form Japan and Europe, 61.0 16 and 63.79 years old 17 , respectively. However, in India, it is 51.6 years old 18 , lower than that in most other regions around the world.…”

Section: Discussioncontrasting

confidence: 44%

Association of smoking using with ALS risk and prognosis in China

Deng

et al. 2022

Preprint

View full text Add to dashboard Cite

Objectives Cigarette smoking using have been posited as possible risk factors for amyotrophic lateral sclerosis (ALS), but few epidemiological studies supporting this hypothesis in China. We therefore explored the association between smoking with ALS incidence and prognosis in Chinese patients. Design Population–based case–control study. Setting, participants We performed a population–based case–control study in 812 ALS patients and 1500 matched controls. All the objects were recruited from Peking University Third Hospital, from January 2011 to December 2018 throughout China. Outcome measures Demographic data and information about premorbid cigarette smoking habits were collected at the time of diagnosis. The association of smoking with ALS was investigated using logistic regression analysis. Kaplan–Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors. Results Current smokers had an increased risk of ALS (odds ratio ≡1.66, 95% confidence interval (CI): 1.46, 1.87) compared to never smokers. Current cigarette pack years≥20 had a significantly shorter median survival (63.89 months, IQR 55.90–71.87) compared with current cigarette pack years≥20 (81.09 months, IQR 77.35–84.84) (p<0.001). Smoking habits were retained in Cox multivariable model. Conclusions Our study has proved current smoking is associated with an increased risk of ALS. Current cigarette pack years≥20 is an independent negative prognostic factor for survival, with a dose–response gradient. Its influence is irrelevant to the presence of chronic obstructive pulmonary disease (COPD) or to respiratory status at time of diagnosis. These results can be helpful for understanding and preventing ALS.

show abstract

Section: Discussioncontrasting

confidence: 44%

Association of smoking using with ALS risk and prognosis in China

Deng

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The liver is a pivotal metabolic organ that acts as a hub that connects various organs, including skeletal muscle and adipose tissue [ 30 ]. Growing evidence suggests that dysregulated energy metabolism in patients with ALS and mouse models is closely correlated with metabolic abnormalities in disease progression and susceptibility [ 31 , 32 , 33 ]. It has been reported that the activity of Mdh is increased in the synaptosomes and homogenates from the spinal cord and motor cortex in hSOD1 G93A mice in the early stages of the disease [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment with Herbal Medicine and Drug Ameliorates Inflammation and Metabolic Abnormalities in the Liver of an Amyotrophic Lateral Sclerosis Mouse Model

Park

Yang

2022

Antioxidants

View full text Add to dashboard Cite

To date, no effective drugs exist for amyotrophic lateral sclerosis (ALS), although riluzole (RZ) and edaravone have been approved for treatment. We previously reported that Bojungikgi-tang (BJIGT) improved motor activity through anti-inflammatory effects in the muscle and spinal cord of hSOD1G93A mice. Therefore, whether combined treatment with BJIGT and RZ synergistically affects liver function in hSOD1G93A mice was investigated. Two-month-old male hSOD1G93A mice were treated with BJIGT (1 mg/g) and RZ (8 μg/g) administered orally for 5 weeks. Drug metabolism and liver function tests of serum and liver homogenates were conducted. mRNA expression levels of cytochrome P450 (CYP) isozymes, inflammatory cytokines, metabolic factors, and mitochondrial oxidative phosphorylation (OXPHOS) subunits were examined using qPCR and Western blotting. Combined administration of BJIGT and RZ did not alter mRNA expression levels of drug-metabolism-related isozymes (CYP1A2 and CYP3A4) but significantly decreased the activity of liver-function-related enzymes (AST, ALT, ALP, and LDH). Increased expression of inflammatory cytokines (IL-1β, TNF-α, and IL-6) and of intracellular stress-related proteins (Bax, AMPKα, JNK, and p38) was reduced by the combined treatment in hSOD1G93A mice compared to that in control mice. Combined administration reduced the mRNA expression of metabolism-related factors and the expression of OXPHOS subunits. Elevated ATP levels and mitochondrial-fusion-associated protein were decreased after co-administration. Co-administration of BJIGT and RZ did not cause liver damage or toxicity but rather restored liver function in hSOD1G93A mice. This suggests that this combination can be considered a candidate therapeutic agent for ALS.

show abstract

“…Hypermetabolism identified via FDG-PET clearly occurs in skeletal muscle and low brain motor areas in ALS. [110][111][112][113][114][115] When added to the widespread evidence for increased resting energy expenditure in ALS detected via indirect calorimetry (including in early-stage patients), [116][117][118][119][120][121][122][123] hypermetabolism is one of the major documented ALS phenomena. While indirect calorimetry does not point to a specific mechanism, FDG-PET directly points to excessive transporter-mediated glucose uptake.…”

Section: Version 3 January 2023mentioning

confidence: 99%

Insulin in Amyotrophic Lateral Sclerosis: Impairment, Tests and Treatment

Rappoport¹

2023

Preprint

View full text Add to dashboard Cite

Background. Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods. A thorough manual examination of the relevant literature, covering over 35,000 papers. Results. Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion. Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

show abstract

The hypometabolic state: a good predictor of a better prognosis in amyotrophic lateral sclerosis

Cited by 15 publications

References 49 publications

Association of smoking using with ALS risk and prognosis in China

Association of smoking using with ALS risk and prognosis in China

Combined Treatment with Herbal Medicine and Drug Ameliorates Inflammation and Metabolic Abnormalities in the Liver of an Amyotrophic Lateral Sclerosis Mouse Model

Insulin in Amyotrophic Lateral Sclerosis: Impairment, Tests and Treatment

Contact Info

Product

Resources

About