Mechanism behind neuron death in motor neurone disease and frontotemporal dementia discovered

Cambridge: Scientists have identified the molecular mechanism that leads to the death of neurons in amyotrophic lateral sclerosis (also known as ALS or motor neurone disease) and a common form of frontotemporal dementia.
"This was a very exciting set of experiments where we were able to apply cutting edge tools from physics, chemistry and neurobiology to understand how the FUS protein normally works in nerve cells, and how it goes wrong in motor neurone disease and dementia" Peter St George-Hyslop

Ambitious research project trials promising new therapy for motor neurone disease

Sheffield: Researchers from the University of Sheffield‘s Institute for Translational Neuroscience are involved in an ambitious European research project aimed at finding a new treatment for motor neurone disease (MND). The collaboration between world-leading academic research groups aims to identify the therapeutic potential of a molecule (interleukin-2) that occurs naturally in our bodies and helps to regulate our immune system and the inflammation that contributes to motor neurone injury in MND.

Weight management is critical for survival in motor neuron disease

Sheffield: Researchers from around the UK, led by a team at the University of Sheffield’s Institute for Translational Neuroscience (SITraN), have found new evidence to support early nutrition management in motor neuron disease (MND). The first UK wide study into tube feeding in MND (ProGas) has found that MND patients benefited most from enteral feeding when they had lost less than 10 per cent of their body weight before the intervention.

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones. The mean age of onset is about 60. ALS usually present with dysarthria and dysphagia for solid or liquids (bulbar onset), and limb symptoms (muscle weakness and spasticity). Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases.
More about  amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (in short)

• Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. 
• Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. 
• The mean age of onset for sporadic ALS is about 60 years. 
• Overall, there is a slight male prevalence (M:F ratio~1.5:1). 
• Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. 
• Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait.
• Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. 
• Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. 
• Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. 
• The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. 
• The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in degenerating lower motor neurones. 
• Signs of upper motor neurone and lower motor neurone damage not explained by any other disease process are suggestive of ALS. 
• The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. 
• Riluzole (Rilutek, Riluzole Zentiva) is the only drug that has been shown to extend survival. 

Source: Lokesh C Wijesekera and P Nigel Leigh. Orphanet Journal of Rare Diseases

Amyotrophic lateral sclerosis

Source: Lokesh C Wijesekera and P Nigel Leigh. Orphanet Journal of Rare Diseases

 

Disease names

Amyotrophic lateral sclerosis (ALS), Motor neurone disease (MND), Charcot's disease, Lou Gehrig's disease

Included diseases

Amyotrophic lateral sclerosis (ALS) is a term used to cover the spectrum of neurodegenerative syndromes characterised by progressive degeneration of motor neurones. However, it is also the term used in modern clinical practice to indicate the commonest form of the disease, Classical (Charcot's) ALS.