Dr Pedro Machado
Department of Neuromuscular Diseases
UCL Queen Square Institute of Neurology
- Joined UCL
- 19th Apr 2010
My research interests include the investigation of new therapeutic strategies and the assessment and prediction of outcomes in rheumatic diseases, with a focus on muscle diseases and axial spondyloarthritis (axSpA). My published research work includes the development and validation of the Ankylosing Spondylitis Disease Activity Score (ASDAS), the study of the relationship between MRI inflammation, MRI fat deposition and progression of structural damage in axSpA, the validation of MRI as a biomarker in muscle diseases, and the development of a new therapeutic strategy targeting protein homeostasis in Inclusion Body Myositis.
As part of my post-doctoral research, I conducted an early phase clinical trial (Science Translational Medicine 2016) in sporadic Inclusion Body Myositis (IBM) with a drug that targets protein dyshomeostasis. IBM is an incurable disease that causes progressive muscle weakness leading to severe disability and dependency. Following this pilot study, I contributed to securing $1.6m from the US Food and Drug Administration (FDA) Orphan Products Division to begin a full-scale randomised placebo-controlled clinical trial. If successful, this trial could result in the first drug treatment available to treat patients with IBM. Together with the MRC Centre for Neuromuscular Diseases MRI team I reported on the sensitivity of MRI to track disease progression in patients with IBM (Lancet Neurology 2015). This study showed the value of MRI to monitor disease progression and set the stage for its potential use in clinical trials in muscle conditions and for exploring the path for biomarker qualification (e.g. their approval by the FDA/EMA), with the ultimate goal of using MRI measures as surrogate endpoints in clinical trials.
As part of my PhD, I validated cut-offs for a new disease activity measure for patients with axial spondyloarthritis (axSpA) including ankylosing spondylitis (AS) (Annals of Rheumatic Diseases [ARD] and Arthritis & Rheumatology 2010-2015). This new outcome measure has better measurement properties and it improved the assessment and management of patients with axSpA/AS. I published the largest and most detailed MRI study to date investigating the processes that drive structural progression (i.e. new bone formation and spinal fusion) in axSpA/AS (ARD 2015). This study elucidated the link between inflammation and structural damage, by specifically looking at the relationship between MRI inflammation, MRI fat deposition and new bone formation in this disease. I found that smokers had a more severe clinical and imaging phenotype (ARD 2012). Taking into account that smoking is a modifiable lifestyle factor, my work suggested that axSpA/AS patients who smoke should be strongly advised to quit this habit, since there may be disease-specific harms of smoking that go beyond the well-known risks described for the general population.
1. Teacher & Organiser of the European League Against Rheumatism (EULAR) Annual Epidemiology Course.
2. Teaching for the MSc/MRes Neuromuscular Disease Programme, UCL Institute of Neurology: a) Convenor of the module “Skeletal Muscle and Associated Diseases”; b) Talks for the “Skeletal Muscle and Associated Diseases Module”: 1) “Acquired Myopathy - Inflammatory Myopathies”; 2) “Inclusion Body Myositis”; 3) “Myofibrillar Myopathies”; c) Talk for the “Motoneurons, Neuromuscular Junctions and associated diseases” Module: 1) “Setting up Clinical Trials in MND and Neuromuscular Diseases”.
3. Teaching for the MRes in Translation Neurology and MSc Brain and Mind Sciences, UCL Institute of Neurology: a) Talk “Clinical Research in Neuromuscular Diseases” from the “Experimental Neurology” module.
4. Teaching for the “Research Methods and Critical Appraisal” Module (shared by various MSc/MRes programmes), UCL Institute of Neurology, with the talk “Comparing groups (between 2 means: paired & unpaired, between 2 or more proportions))”.
5. Teaching for the Update in Neuromuscular Disorders annual course, UCL Institute of Neurology: “Inclusion Body Myositis Update”.