Research Impact


Developing new diagnostic services and treatments for rare muscle diseases 

12 December 2014


UCL research has delivered rapid and reliable diagnostics for rare but disabling muscle conditions, and underpinned the establishment both of a new national reference laboratory and of the only UK NHS centre for diagnosis and management of these diseases. It is now being used to develop new treatments for them.

Understanding and finding treatments for rare disease represents a major challenge across medicine. Among the conditions for which new and better treatments are required are episodic neurological diseases, including genetic muscle channelopathies. These rare but disabling disorders, which result from functional disturbances of ion channels or the proteins that regulate them, affect around 1 in 50,000 people worldwide. Patients experience debilitating episodes of muscle paralysis and/or severe stiffness; over time, permanent muscle weakness may result in significant disability.

Because they are so rare, accurate diagnosis of these episodic conditions is difficult. It requires specialist clinical, genetic and electrophysiological assessment, the latter involving detailed measurement of the electrical properties of relevant cells and tissues. In the absence of these highly specialised assessments misdiagnosis is common, the variable severity and intermittent nature of some symptoms leading to erroneous suggestions of psychological origins. As a result, patients often experience a long delay before a correct diagnosis is achieved and effective treatment instituted.

World-leading collaborative research established and led by Professor Michael Hanna (UCL Institute of Neurology) has helped to redress this problem by elucidating the genetic architecture and identifying new disease mechanisms for genetic muscle channelopathies. By significantly progressing fundamental understanding of the pathophysiology of such diseases, it has resulted in the development of in new tests supporting faster diagnosis and better patient outcomes.

The research, which has included gathering and working with the world's largest cohort of over 1,800 families with inherited channelopathies, has identified hundreds of unique mutations in the specific genes responsible for them and pinpointed their relationships to a range of episodic muscle conditions. Its demonstration of the need to tailor therapy for these diseases to individual genotype has been used to direct more effective therapy selection, with clear, positive impacts for patient.

As a result of their expertise in this field, the UCL team was commissioned by NHS Highly Specialised Services to provide the UK's only diagnostic and treatment centre for channelopathies. The centre is now also the only UK national reference laboratory for genetic muscle channelopathies. Supported by more than £6 million of Department of Health funding, it offers novel and efficient diagnostic services supporting rapid diagnosis and gene testing selection. More than 8,000 genetic tests and 1,000 electrophysiological tests have been performed on patients since the service began.

As well as diagnostic services, the centre also offers a clinical service which provides one-stop, same-day assessments and subsequent electrophysiological testing for more than 2,000 patients. With informed consent, and supported by follow-up genetic counselling and treatment, patients are then offered genetic testing to achieve a DNA-based diagnosis. The clinical service provided here has defined best practice in treating patients with these rare conditions: by providing accurate individual diagnoses it ensures that they receive the most effective medications for their particular condition, often significantly improving their quality of life.

The research team is also involved in the development of a potential new treatment for muscle channelopathy, based on their leadership between 2008 and 2011 of the first international randomised controlled trial for such a treatment. The results of the trial, which identified a drug called mexiletine as an effective treatment for muscle channelopathy, were published in 2012 and attracted significant attention both within the scientific community and among patient groups. The team has since managed to obtain exclusive Orphan drug indication for mexiletine from the European Medicines Agency, a critical step in enabling and supporting the process for full marketing authorisation and European licensing of the drug to treat muscle channelopathy patients.

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