Research Programme

Molecular pathogenesis of neuromuscular disease Active programmes of clinical and molecular genetic research on disorders of skeletal muscle and peripheral nerve are undertaken in the Department of Molecular Neuroscience at the Institute of Neurology  and are closely linked to the clinical service provided by the Centre for Neuromuscular Disease. Our research programme is to be consolidated and expanded as part of the new Medical Research Council Centre for Translational Research in Neuromuscular Disease.

The Institute of Neurology, Queen Square

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Muscle Disease

Mitochondrial Disease

Prof Mike Hanna, Prof Tony Schapira, Dr Shamima Rahman

There is a long history of research into mitochondrial respiratory chain disease at IoN and this area continues to be active. Although we continue to identify a large number of genetic defects in mitochondrial DNA as the cause of mitochondrial myopathies, in recent years we have focussed on the role of the nuclear genome and on the molecular pathogenesis of these disorders. In collaboration with colleagues at ICH and in Newcastle we have defined the importance of a recently identified nuclear gene responsible for mtDNA replication in human mitochondrial diseases. In collaboration with Professor Duchen at UCL we have developed new systems to evaluate mitochondrial membrane potential in culture human muscle cells from patients with mitochondrial disorders caused by mtDNA defects. This work has uncovered a potential new mechanism of ATP hydrolysis in mitochondria in the pathogenesis of mitochondrial disease. In autumn 2006 we received national recognition for our clinical and genetic mitochondrial service with the award of permanent funding through national specialist commissioning from the department of health. This provides 2 million sterling recurrent annual funding to provide a national service for this group of patients and is collaboration between our group and colleagues in Oxford and Newcastle.

Ion Channel Disease

Prof Mike Hanna, Prof Dmitri Kullmann

An active programme of externally funded research into human muscle ion channel diseases continues. These muscle disorders cause patients to have combinations of disabling paralysis, muscle stiffness and cardiac arrhythmias. We undertake genetic and molecular expression studies (in collaboration with Professor Kullmann, ION) allowing elucidation of the molecular mechanisms in these conditions.

In 2001 we received national recognition for the clinical arm of this research by the award of NCG status to provide the UK clinical and diagnostic service for muscle channelopathies. We have expanded this work to include NIH funded natural history studies and clinical trials in these disorders. In collaboration with Professor Wood and Professor Kullmann at the Institute of Neurology we have also developed the major UK research centre for CNS genetic channelopathies.

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Peripheral Nerve Research

Dr Mary Reilly, Dr Henry Houlden

Charcot Marie Tooth Disease (CMT)

Our major research interest in peripheral neuropathies is the molecular basis of the inherited peripheral neuropathies of which CMT is the commonest. Although we continue to identify new mutations in many of the common genes that cause CMT, in recent years we have focused on the rare forms of CMT. There are currently over 30 causative genes for CMT and 26 of these are defined as rare. As well as searching for disease causing mutations, a major focus of our research is on phenotype / genotype correlations to try to understand the pathogenesis of these rare forms of CMT. With this in mind we also run the only dedicated inherited neuropathy clinic in the UK in the centre for neuromuscular disease at NHNN from where we recruit many of our patients.

We have just obtained external funding to run the first therapeutic trial in the UK in CMT which will be commencing in November 2006. This trial is being done in collaboration with colleagues in Italy. Before starting the trial we developed a specific impairment and disability scale for CMT patients (CMTNS) together with colleagues in the US. This scale will be the primary outcome measure for the trial.

Hereditary Sensory and Autonomic Neuropathies

We have an active programme of research into the HSAN’s. These diseases are not as common as CMT but can be very disabling for patients. As well as searching for disease causing mutations in the five genes described to cause HSAN, we also study phenotype / genotype correlations to try to understand these disorders better. We have recently completed a large genotype / phenotype study of HSAN type 1 which revealed some interesting features including a more severe phenotype in males which we are currently investigating further. We have also identified a new causative gene for HSAN in a spontaneous rat model of the disease and are investigating the role in humans currently.

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National Hospital for Neurology and Neurosurgery

University College London Hospitals NHS Trust

Institute of Neurology