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Motor neurone disease: devastating, mysterious and few treatments available

15.06.2007
Motor neurone disease (MND), also known as amyotrophic lateral sclerosis, is a degenerative disease of unknown cause which causes patients to lose basic motor functions and has a devastating effect on them and their families. But work is ongoing on new treatments to prolong life expectancy and raise quality of life for patients, say the authors of a Seminar published in this week’s edition of The Lancet.

And soldiers, Italian professional footballers and the Chamorro population of the Pacific Island of Guam have been reported to be more at risk of MND than the general population.

Professor Douglas Mitchell, Motor Neurone Disease Care and Research Centre, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK and Professor Gian Borasio, Motor Neurone Research Group, Department of Neurology, Munich University, Germany, comprehensively reviewed literature published on MND since 2000 to prepare the Seminar.

MND is one of the major neurodegenerative diseases alongside Alzeheimer’s disease and Parkinson’s disease. It is a progressive disorder that involves degeneration of motor functions at all levels as the motor neurones of the nervous system are destroyed.

The authors: “The course of the disorder is inexorably progressive, with 50% of patients dying within three years of onset.”

Symptoms generally begin in one or more of three regions – the throat/jaw area (bulbar), the arm area (cervical) or the leg area (lumbar). Bulbar-onset patients can struggle to swallow, have slurred speech, and/or facial weakness. Cervical-onset patients have problems with the use of their arms and hands and lumbar-onset patients have difficulty with walking.

Progression of the disease is marked by loss of speech, chronic nocturnal hypoventilation, daytime fatigue, general loss of strength and motor functions. Up to 73% of MND patients complain of pain. Psychosocial care is also vital for patients, with 100% of patients in one study mentioning family as important to their quality of life.

Men are more likely to get MND than women (approximate ratio 1.6:1) and MND has been more common in certain populations, such as the Chamorro population on the Pacific island of Guam. It has been suggested that this is because the diet of these people includes the fruit bat, which feeds on cycad seeds. These seeds contain methylaminoalanine, which is thought to have a role in MND. An increased risk of MND has also been reported in military personnel and Italian professional football players.

Heavy-metal toxic effects, and environmental and occupational exposures, have also been proposed as causes of MND. But the authors say: “Despite extensive research, the disorder remains poorly understood in terms of a unifying causal hypothesis, and, indeed, might turn out to be a common end-stage phenotype of diverse causes.”

Many treatments have been tried for MND, but few have had success. Riluzole is the only drug licensed to treat MND, and has been shown to extend the lives of MND patients by an average of three months.

The authors are sceptical about the use of stem cell treatment, saying much work needs to be done before stem-cell treatment can ever be regarded as even an experimental therapeutic treatment. An earlier trial of injecting stem-cells into the spinal cord proved ineffective in relieving MND symptoms.

Use of viral vectors for drug delivery could be a pioneering MND treatment, since it extended the life expectancy of mice it was tested in by 30%. The need to deliver disease-modifying treatments direct to the site of disease process – i.e. the motor neurone – is a recurring theme of treatment discussions.

The authors conclude: “Because of the shortage of satisfactory disease-modifying treatments, early diagnosis of amyotrophic lateral sclerosis has traditionally not been imperative. It will, however, be increasingly important for any attempts to develop more effective treatments.”

Tony Kirby | alfa
Further information:
http://www.thelancet.com/webfiles/images/clusters/thelancet/press_office/Seminar.pdf

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