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MattJ
11th February 2012, 14:30
Highlights

http://alsn.mda.org/news/sma-gene-associated-sporadic-als


The SMN1 gene, when deleted or mutated, causes a deficiency of SMN protein, which is the underlying cause of spinal muscular atrophy (SMA).
ALS (amyotrophic lateral sclerosis) and SMA both are diseases in which motor neurons degenerate and die, leading to muscle weakness and paralysis.
A team of scientists has demonstrated that extra copies of the SMN1 gene play a role in sporadic (noninherited) ALS.
More research is necessary to determine the basis of the correlation between extra copies of SMN1 and increased risk of sporadic ALS; discoveries could point to additional targets and strategies in ALS drug development.


Duplications (extra copies) of the SMN1 gene are a "major" risk factor for developing sporadic (noninherited) ALS (amyotrophic lateral sclerosis), a team of scientists based in the Netherlands and United Kingdom has reported.

The SMN1 gene also is implicated in the motor neuron disease spinal muscular atrophy (SMA). Deletions or mutations in the SMN1 gene (SMN stands for "survival of motor neurons") lead to a deficiency of SMN protein and are the underlying cause of SMA.

ALS and SMA both are diseases in which muscle-controlling nerve cells called motor neurons degenerate and die, leading to profound muscle weakness and, eventually, paralysis.

The research team, including corresponding author L.H. van den Berg at the University Medical Center Utrecht in Utrecht, the Netherlands, described its findings online Feb. 8, 2012, in Neurology. (See SMN1 gene duplications are associated with sporadic ALS.)

Further research is needed to determine how SMN1 gene duplications raise the risk of developing ALS, and any potential for SMN1-based ALS biological markers (biomarkers) or therapies.

'Significant increased risk'

Researchers examined copy numbers of SMN1 and the similar SMA-associated gene SMN2 in 847 people with confirmed sporadic ALS and in 984 people without the disease. They found that the risk of developing ALS in those with SMN1 duplications (three copies) was approximately double that of people without the duplications. (The odds of developing ALS over a lifetime are 1 in 350 for men, and 1 in 450 for women.)

There was no effect on disease susceptibility for those with only one copy of the SMN1 gene, and no correlation between SMN2 copy number and ALS risk.

The investigators also studied 814 people from the original group with confirmed ALS to determine whether SMN1 or SMN2 copy number has an effect on disease onset or progression. Results showed that neither deletions nor duplications of SMN1 or SMN2 had any effect on survival time or age at onset in sporadic ALS.

The mechanism by which SMN1 duplications increase the risk of sporadic ALS currently is unknown, but the study team proposed a number of possible explanations, including:


High levels of SMN protein could interfere with the cellular processing of genetic instructions.
SMN1 duplications produce higher SMN protein levels that are toxic to motor neurons.
SMN1 duplications don't increase risk of ALS by changing SMN protein levels, but by complex interactions with other genes or environmental factors.

For more on the mechanism by which SMN1 duplications might cause susceptibility to ALS, read More can be less: SMN1 gene duplications are associated with sporadic ALS, also published Feb. 8, in Neurology (fee required).

Meaning for people with ALS

Further study is needed to determine how extra copies of SMN1 increase the risk of developing sporadic ALS. In the meantime, the identification of the risk factor provides the opportunity for genetic testing to determine ALS risk or help speed diagnosis.

The new findings also provide scientists with potential targets and additional avenues to pursue in the development of ALS therapies.http://alsn.mda.org/news/sma-gene-associated-sporadic-als

pete
11th February 2012, 14:51
Highlights

http://alsn.mda.org/news/sma-gene-associated-sporadic-als


The SMN1 gene, when deleted or mutated, causes a deficiency of SMN protein, which is the underlying cause of spinal muscular atrophy (SMA).
ALS (amyotrophic lateral sclerosis) and SMA both are diseases in which motor neurons degenerate and die, leading to muscle weakness and paralysis.
A team of scientists has demonstrated that extra copies of the SMN1 gene play a role in sporadic (noninherited) ALS.
More research is necessary to determine the basis of the correlation between extra copies of SMN1 and increased risk of sporadic ALS; discoveries could point to additional targets and strategies in ALS drug development.

http://alsn.mda.org/news/sma-gene-associated-sporadic-als

Hi Matt

I will stay tuned ?

pete

MattJ
11th February 2012, 14:51
Just searching on the t'internet like you do and came across the following article from 2006:

http://www.ncbi.nlm.nih.gov/pubmed/16931506


BACKGROUND: SMN1 gene deletions cause spinal muscular atrophy, and SMN2 gene deletions have been associated with sporadic lower motor neuron diseases.

OBJECTIVES: To study the frequency of abnormal SMN1 gene copy numbers and to determine whether SMN2 gene modulates the risk of amyotrophic lateral sclerosis (ALS) or the duration of evolution.

CONCLUSION: Abnormal SMN1 gene copy numbers are a genetic risk factor in sporadic amyotrophic lateral sclerosis. There was no modulator effect of the SMN2 gene.

Is this just me but has the new article just come to the same conclusion?! If so, what a jeffing waste of time. No wonder nothing advances when you see duplicate research like this.

pete
11th February 2012, 14:55
Just searching on the t'internet like you do and came across the following article from 2006:

http://www.ncbi.nlm.nih.gov/pubmed/16931506

Is this just me but has the new article just come to the same conclusion?! If so, what a jeffing waste of time.

Matt deja vu or what

pete

MattJ
11th February 2012, 15:23
Deja ruddy vu!

Interestingly I came across Isis Pharmaceuticals who are performing trials in ALS and SMA:

http://www.isispharm.com/Pipeline/Therapeutic-Areas/Neurodegenerative-Disease.htm

The ISIS-SOD1 trails is something to watch, as it targets familial ALS, but more interestingly they are also trialling a drug to treat SMA.


ISIS-SMNRx is an antisense drug designed to treat SMA, a severe motor-neuron disease that is the leading genetic cause of infant mortality.

SMA is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene leading to a decrease in the protein, survival motor neuron (SMN). SMN is critical to the health and survival of nerve cells in the spinal cord that are responsible for neuro-muscular growth and function.

ISIS-SMNRx is designed to treat all types of childhood SMA by altering the splicing of a closely related gene (SMN2) that leads to the increased production of fully functional SMN protein. A long way off, but if this trial shows efficacy, could this potentially benefit patients with sporadic MND / ALS who test positive for the deleted / mutated SMN1 gene.

Oh and guess who features here again...Biogen. How many fingers in how many pies!!!

john
11th February 2012, 17:11
Matt,
there is a thread going on in ALSTDI forum talking about what is needed in research and one of the themes is the need for a database available to researchers. The idea is to stop duplicated effort. This looks like possiblly 3 groups ( it may be biogen are following on from the 2006 research) doing the same thing. It was suuggested researchers report successes and failures to save this sort of effort and money being wasted.
Someone else suggetsed funding should not be given to the pharmaceutical sector to research and this should be left to labs researching for a cure not something deemed commercially viable. As things are no one will do any controlled research on sodium chlorite because there is no money in it.

john

computatec
11th February 2012, 18:36
Is this just me but has the new article just come to the same conclusion?! If so, what a jeffing waste of time. No wonder nothing advances when you see duplicate research like this.

Hello Matt, I think this illustrates the snails pace at which much research proceeds.

Clive

pete
11th February 2012, 19:35
Hi all,

Kinda makes you ask the question who is paying who,, and who dictates the research pace ???

pete.

jadedjohn
11th February 2012, 22:25
With just over 3 million spent on research in the uk what can we expect! That's why I'm trying my hardest to raise as much as I can - only raised 2% of the target :-(. Maybe if we all I'd a bit more campaigning to raise th profile we might get somewhere.

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