Translating Amyotrophic Lateral Sclerosis Genetics to the Clinic: Implications for the Patient

Abstract

Ammar Al-Chalabi is Professor of Neurology and Complex Disease Genetics at King’s College London (London, UK) and Director of the King’s Motor Neuron Disease Care and Research Centre. Al-Chalabi received his medical degree from Leicester University (Leicester, UK) graduating with distinctions and prizes. He won a prestigious Medical Research Council Clinical Training Fellowship, allowing him to combine clinical and scientific training, culminating in a PhD on genetic risk factors for amyotrophic lateral sclerosis (ALS), awarded by the University of London (London, UK). He was awarded the MNDA Charcot Young Investigator Award, an international competitive prize, for this work. He completed his specialist training in neurology at various London hospitals, including the National Hospital for Neurology and Neurosurgery, Queen Square (London, UK). He won a high-status Medical Research Council Clinician Scientist Fellowship, allowing him to begin his independent research career at King’s College London, working with Nigel Leigh and Chris Shaw. He spent a year at Harvard Medical School and Massachusetts General Hospital (MA, USA) in the laboratory of Robert H Brown Jr, and became a course leader and Instructor in Complex Disease Genetics at Cold Spring Harbor Laboratory (NY, USA). He was subsequently elected to the Fellowship of the Royal College of Physicians. For the last 18 years, Al-Chalabi’s clinical and laboratory research has focused on understanding genetic and other risk factors for ALS, investigating why and how the disease manifests and running clinical trials. He was directly involved in the first two studies to discover that chromosome 9 held the location of a new ALS gene in some families, and led an international effort to successfully narrow down the location of the gene, which was the most crucial step in its discovery. It is now regarded as the most important ALS gene and known as C9ORF72. His clinical practice is based at King’s College Hospital Motor Nerve Clinic (London, UK), a multidisciplinary clinic specializing in adult motor neuron diseases, accredited by both the Motor Neurone Disease Association (UK) and ALS Worldwide (USA). Orla Hardiman is a HRB Clinician Scientist, Clinical Professor of Neurology at Trinity College (Dublin, Ireland) and Consultant Neurologist at the National Centre for Neuroscience (Dublin, Ireland) where she leads the ALS programme. She is the recipient of the AAN Sheila Essey Award for her contribution to ALS research and the International Alliance of ALS/MND Forbes Norris Award for her contribution as a clinician and researcher. She is Editor-in-Chief of the ALS Journal, which is the official publication of the World Federation of Neurology Subgroup on ALS/MND, and is author of over 150 peer-reviewed publications. The primary research interests of Hardiman’s group include the epidemiology and pathogenesis of ALS, with particular reference to the identification of genetic and environmental susceptibility factors. A recent focus of the group has been on the clinical and genetic overlap between ALS and frontotemporal dementia and the use of deep phenotyping to identify clinically relevant biomarkers.