ESPEYB15 14 Science and Medicine Who could have predicted it? (1 abstracts)
Sobell Department of Motor Neuroscience, University College London Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK
To read the full abstract: Lancet 2017;390:1664-1675
Whoever could have imagined that a compound discovered as being secreted by enteroendocrine cells in the gut could have a role in treating Parkinson’s disease? GLP-1 does indeed have diverse actions on several peripheral organs (including tongue, stomach, adipose tissues, muscle, pancreas and liver) and on the brainstem to regulate food consumption and glycaemia. Pre-clinical studies in rodents had shown apparent effects of GLP-1 on promoting neurite outgrowth and protecting hippocampal neurons from apoptotic insult, and even stimulating adult neurogenesis, particularly of neurons positive for tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis. The positive findings of this randomised, placebo-controlled trial of exenatide, administered peripherally at licensed diabetes doses, open new treatment avenues for neurological diseases and highlight the remarkable gut-brain axis: the close synergy in biochemical signaling between these organs.
From a broader perspective, the identification of unanticipated alternative treatment targets for existing medicines can be lucrative for companies. Alternatively, the emergence of unanticipated off-target side effects can destroy a promising new agent, often late in the pharmacological pipeline after costly investment, and can prove much more costly for companies and patients if discovered by post-marketing surveillance. ‘Genomic target validation’ is an alternative hypothesis-free approach that aims to flush out unanticipated drug effects, whether good or bad, at a much earlier stage of drug development, and has attracted recent major investments https://www.gsk.com/en-gb/media/press-releases/gsk-and-23andme-sign-agreement-to-leverage-genetic-insights-for-the-development-of-novel-medicines/.