Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration–motor neuron disease - Luty - 2010 - Annals of Neurology - Wiley Online Library

New dementia gene linked to existing drugs
Analysis of a study published in a science journal | By Dr Philippa Brice | Published 2 November 2010

Study: Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration – motor neuron disease
By: Luty A.A. et al. (19 authors total)
In: Annals of Neurology
Link: http://dx.doi.org/10.1002/ana.22274
What this study set out to do:

Researchers looked for new mutations in selected candidate genes that might account for an inherited form of early-onset dementia.

How they went about it:

Frontotemporal lobar degeneration (FTLD) is the most common cause of early-onset dementia and the third most common form of dementia (after Alzheimer’s disease and dementia with Lewy bodies). A large family with an inherited form of FTLD with no mutations in genes previously linked to dementia were examined for mutations in other candidate genes, and for the biological effects of these presumed mutations.

Outcome:

The researchers found a mutation in the Sigma nonopioid intracellular receptor 1 (SIGMAR1) gene in affected individuals. This was shown to cause increased expression of the Sigma-1 protein in the brain, which in turn altered the distribution of other proteins observed in brain lesions characteristic of this form of dementia and of motor neuron disease (MND). This was modified on treatment with ligands of the Sigma-1 receptor.

Conclusion:

The authors conclude that mutations in the SIGMAR1 can cause a form of familial FTLD-MND, although they say it is not possible to say that this the main genetic locus associated with the more common, non-familial forms of these neurological disorders. However, they also note that drugs that target the Sigma-1 receptor might be effective as treatments for these conditions.

Our view:

Drugs directed against the Sigma-1 receptor already exist and are used for the treatment of various psychiatric disorders. Researchers are reportedly testing them in mice to see whether they have any effect on the development of brain lesions associated with dementia or motor neuron disease. If they did – and this remains a big if for now – then clinical trials in humans to assess whether they would be effective in delaying the progression of forms of dementia and MND could potentially proceed quite rapidly.
Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration–motor neuron disease – Luty – 2010 – Annals of Neurology – Wiley Online Library