Ghrelin as a treatment for amyotrophic lateral sclerosis

Abstract

Ghrelin is a 28-amino acid hormone that is predominantly secreted by oxyntic glands of the stomach and gastrointestinal tract. 1 Generally recognised for stimulating growth hormone (GH) secretion 1 and as a key orexigenic regulator of food intake, 2-5 there is growing evidence to highlight wider-ranging biological actions of ghrelin. 6 These actions underscore the potential for the use of ghrelin, and/or the activation of ghrelin-mediated pathways, as a possible therapeutic strategy for conditions that are associated with impairments in appetite and the loss of GH secretion, as well as complex diseases that are associated with impairments in metabolism. In this review, we briefly summarise the biological actions of ghrelin and consider how modulation of the actions of ghrelin could be used to mitigate disease processes central to amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that currently lacks effective treatments.

Associations of postprandial ghrelin, liver‐expressed antimicrobial peptide 2 and leptin levels with body composition, disease progression and survival in patients with amyotrophic lateral sclerosis

“…This would contribute to weight loss, accelerated disease progression, and earlier death. This is relevant given speculation of ghrelin‐axis modulation as a potential treatment in ALS [14, 43, 44], and recent findings suggesting that increased LEAP2:ghrelin ratios may contribute to impaired neuronal function [45]. Results provide impetus for the conduct of studies aimed at improving understanding of ghrelin biology in ALS.…”

“…Ghrelin is best known for its orexigenic effects following binding and activation of the growth hormone secretagogue receptors (GHSRs) [14][15][16] (Figure 1). While levels of plasma ghrelin are dynamically affected by feeding status, rising preprandially and falling postprandially [17,18], overall ghrelin levels are lower in obesity [19].…”

Appetite and quality of life in amyotrophic lateral sclerosis: A scoping review

“…Weight loss is considered a challenge for people with amyotrophic lateral sclerosis (pALS) and has been identified as a negative prognostic factor that influences mortality and morbidity 1–5 . A myriad of causes for early weight loss have been identified, including dysphagia related to bulbar‐onset disease, metabolic imbalance (eg, increased energy expenditure), and central mechanisms including hypothalamic degeneration 2,6,7 . Together, these factors contribute to weight loss and muscle wasting that may worsen disease progression and outcomes 6 .…”

“…[1][2][3][4][5] A myriad of causes for early weight loss have been identified, including dysphagia related to bulbar-onset disease, metabolic imbalance (eg, increased energy expenditure), and central mechanisms including hypothalamic degeneration. 2,6,7 Together, these factors contribute to weight loss and muscle wasting that may worsen disease progression and outcomes. 6 Previous studies of nutritional interventions targeting weight loss have shown increased survival rates, further supporting the need to address weight loss for pALS.…”

“…2,6,7 Together, these factors contribute to weight loss and muscle wasting that may worsen disease progression and outcomes. 6 Previous studies of nutritional interventions targeting weight loss have shown increased survival rates, further supporting the need to address weight loss for pALS. 1,8 The symptom of appetite loss has been identified as one cause of weight loss and reported in up to two thirds of pALS.…”