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Disease process

MND is increasingly thought of as a disease of several aetiologies, where a complex interaction between multiple components activates a pathway which results in neuronal cell death (Cox and others 2007).

Turner and others 2013

The enormous advances in scientific research during the past two decades have revealed the complexity of ALS pathogenesis which might have been underestimated at the time of the discovery of SOD1. Developments in molecular biology, particularly the discovery of C9orf72, when combined with new approaches in clinical neurophysiology and neuro-imaging have accentuated rather than lessened the importance of detailed clinical assessment.

The multiple pathogenic processes support the view of multiple routes to a common endpoint of progressive upper motor neuron and lower motor neuron loss, which might mean that successful treatment will ultimately involve multiple targets.

Ravits and others 2013

The holy grail of ALS is rationally designed therapy that effectively stops ALS neurogeneration in its advance. That different gene mutations cause identical clinical phenotypes means that multiple mechanisms exist and ALS is a syndrome. However, that one single gene mutation causes many different ALS phenotypes means that there must be common mechanisms. With the transformative understanding of clinical, neuropathological, and molecular-genetic aspects of ALS over the last five years, this quest for rational fundamental therapy has become a realistic hope.

MND Australia 2014

There are many theories about mechanisms involved in the development of MND.
These include:

  • genetic factors
  • physical trauma
  • protein aggregation
  • glutamate toxicity
  • mitochondrial dysfunction
  • dysfunctional signalling pathways
  • exposure to environmental toxins and chemicals
  • free radical damage
  • infection by viral agents
  • immune mediated damage
  • loss of growth factors required to maintain motor neurone survival

It is thought that they may act individually or in combination to cause the disease.

Research throughout the world is ongoing. This has been underpinned by the development of a number of animal models (e.g. mice, zebra fish) and by DNA and tissue banks (storing DNA, neural tissue and blood samples from people with MND and control subjects).

The use of stem cells and large-scale drug screening for potential value as treatments are developing areas of research.

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