The National Institute of Health (NIHR) Research Rare Diseases Translational Research Collaboration has awarded a total of £650,000 to extend research into rare neurodegenerative and neuromuscular diseases.
Under one of the awards Professor Nick Wood, Director of the BRC Neurosciences programme, will investigate the C9orf72 gene. People with the C9orf72 mutation are at an increased risk of developing amyotrophic lateral sclerosis, a rapidly progressive neurological disease that attacks the nerve cells; or of developing frontotemporal dementia, a rare syndrome where the frontal and temporal anterior lobes of the brain shrink.
In addition, Professor Wood will develop research into the LRRK2 gene. Discovered in 2004, it is the greatest known genetic contributor to Parkinson’s disease.
The other award was made to the rare neuromuscular theme which is led by Professor Michael Hanna, Director of UCL’s Institute of Neurology, where research projects into Duchenne Muscular Dystrophy (DMD) and inclusion body myositis (IBM) have been funded.
The Rare Diseases Translational Research Collaboration is a partnership of NIHR BRCs, biomedical research units and clinical research facilities. The aim is to provide research infrastructure to support translational research into rare diseases. Eleven specific rare disease themes have been identified.
Professor Wood and his team, made up of a consortium of BRCs including Kings College, led by Professor Chris Shaw and Oxford, led by Professor Kevin Talbot, will study people with known mutations of the C9orf72 gene to allow for in-depth phenotype analyses.
Professor Wood said: “Rather than define phenotypes and chase down genes, we have taken the other route. We will study patients and their families with known mutations, permitting a whole range of complex phenotype questions from a simpler genetic background to be addressed”.
Professor Wood’s other study concentrates on the LRRK2 gene. Discovered in 2004, it is the greatest known genetic contributor to Parkinson’s disease. This will also involve the collection of phenotypic data from patient cohorts. The research will be led by Professor Wood and Professor Huw Morris, from the UCL Institute of Neurology, and involve input from Kings College and Oxford BRCs.
Professor Wood said: “We hope to find, in much more detail, the range of phenotypes from a particular mutation which will guide clinical practice in particular diagnosis.”
Under Professor Hanna’s neuromuscular theme within the NIHR Rare Diseases Translational Research Collaboration Professor Francesco Muntoni, supported by the Great Ormond Street BRC will investigate DMD, a severe muscle wasting disease, affecting boys which commences around age three, with death likely by late teens.
Current understanding of DMD recognises some subgroups of patients have more severe forms of the disease, and some have milder forms, yet all have the same genetic mutation. Professor Muntoni and his team will study groups of patients with DMD and measure their particular genetic defects more precisely.
BRC-supported Professor Hanna said: “The DMD programme is going to collect large cohorts nationally through the BRC infrastructure to study their natural history and their genetics accurately. We aim to understand the variation in disease severity and assess variations in treatment response in therapeutic trials”. Professor Hanna went on to say: “This will be a valuable step in the translational pathway for DMD patients”.
The second study will explore IBM, an inflammatory muscle disease depicted by progressive weakness and wasting of both distal and proximal muscles. IBM is an important acquired muscle wasting disease in patients over 45, leading to total immobility over approximately 10 years.
Explaining insights from earlier work, which included studying muscle biopsies of those with IBM, Professor Hanna said: “Based on biopsy studies we have started to understand differences in the severity of IBM and we think this will be important in treatment response”.
Commenting on the value of the NIHR infrastructure, Professor Hanna said: “Through the BRC network we are able to build substantial cohorts of IBM patients and stratify them based on muscle biopsy appearances, clinical assessment and MRI evaluation”.
Professor Hanna went on to explain how BRC work on stratification will be valuable in designing and involving patients in clinical trials: “Based on the BRC’s strong links with industry it is highly likely trials of two new agents will be able to start in the next couple of years.”
