Over the past few days, the news has been full of stories about a "breakthrough" in ALS/MND research, thanks to funding provided by the Ice Bucket Challenge.
The announcement concerns the publication of two Nature papers (see here and here) that examined the genomes of several thousand ALS patients and discovered three new genes and linked one already known, to increased susceptibility for contracting ALS.
Before I go any further, I want to make a distinction. There are two kinds of ALS
1) Genetically acquired ALS is called familial and results from the inheritance of a gene from your mother or father. If either of these had the disease, then you have a 50% chance of carrying the same gene (this doesn't necessarily mean you will develop ALS, just that you are at greater risk). This form of ALS, abbreviated to fALS is uncommon, affecting only between 5–10% of all patients.
2) By far the most common form of ALS is sporadic, meaning we don't know why people get it, and there's no genetic cause. This form is abbreviated to sALS and affects approximately 90% of all patients.
Genes provide a clue but are not the only answer.
Whilst over 20 genes have so far been linked to ALS, to date only 4 have been shown to cause the inherited form of the disease. The other genes so far described are unique to ALS patients but the exact roles they play in disease have not been completely elucidated.
The Nature papers describe three more such genes – they have been found in ALS patients but what they do and how they might influence the aetiology of disease requires more research.
A susceptibility gene for sALS?
The other gene included in the Nature studies, called NEK1, was first identified in 2015. This type of gene is of particular interest to me, since a mutated form of it was found in patients with both types of ALS. The researchers report NEK1 increases patients susceptibility to contracting ALS, thus opening up possibilities for interventions.
This is important because even though the two types of ALS I describe above have different names and are contracted in different ways, the pathologies are the same. So to find a common gene amongst fALS and sALS patients is very important, as it might imply similar pathways for disease progression.
More sobering is that only three percent of patients from both groups had the gene mutation, so it's by no means common.
ALS = genes + environment
I'm an environmental ALS researcher, but I'm not naive enough to think environmental trigger(s) alone are enough to trigger the disease. We've always acknowledged that ALS likely requires a combination of genes and some kind of environmental toxin to trigger pathology. And so here we are – with NEK1, a gene that increases people's susceptibility to ALS.
Could this be the key? Well, it's way too early to say and given this gene mutation was only identified in three percent of patients, it's clearly not the only gene involved in sALS.
Nevertheless, this is yet another clue on the long and complex path to unravelling ALS/MND.