Ghrelin as a treatment for amyotrophic lateral sclerosis

Ghrelin is a gut hormone best known for its role in regulating appetite and stimulating the secretion of the anabolic hormone growth hormone (GH). However, there is considerable evidence to show wider‐ranging biological actions of ghrelin that favour improvements in cellular and systemic metabolism, as well as neuroprotection. Activation of these ghrelin‐mediated pathways may alleviate pathogenic processes that are assumed to contribute to accelerated progression of disease in patients with neurodegenerative disease. Here, we provide a brief overview on the history of discoveries that led to the identification of ghrelin. Focussing on the neurodegenerative disease amyotrophic lateral sclerosis (ALS), we also present an overview of emerging evidence that suggests that ghrelin and ghrelin mimetics may serve as potential therapies for the treatment of ALS. Given that ALS is a highly heterogeneous disease, where multiple disease mechanisms contribute to variability in disease onset and rate of disease progression, we speculate that the wide‐ranging biological actions of ghrelin might offer therapeutic benefit through modulating multiple disease‐relevant processes observed in ALS. Expanding on the well‐known actions of ghrelin in regulating food intake and GH secretion, we consider the potential of ghrelin‐mediated pathways in improving body weight regulation, metabolism and the anabolic and neuroprotective actions of GH and insulin‐like growth factor‐1 (IGF‐1). This is of clinical significance because loss of body weight, impairments in systemic and cellular metabolism, and reductions in IGF‐1 are associated with faster disease progression and worse disease outcome in patients with ALS. Ghrelin, a hormone that is predominantly secreted by oxyntic glands of the stomach, has wide‐ranging biological actions. These actions underscore the potential for the use of ghrelin and/or the activation of ghrelin‐mediated pathways as a therapy for conditions associated with the loss of growth hormone secretion, impairments in appetite and alterations in metabolic homeostasis. Here, we briefly summarise the biological actions of ghrelin with a specific focus on the treatment of amyotrophic lateral sclerosis (ALS; a neurodegenerative disease characterised by the death of upper (UMN) and lower (LMN) motor neurones).