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Re: common cause of als

This is the most significant discovery in ALS research in many years.

My first reaction was a kind of excitement, that there was hope that I would see some benefit from this. I allowed myself to start thinking I may live a long life after all. But I quickly caught myself, and realized that any drug therapy resulting from this would be at least 5 years away, sadly this is too long a wait for me.

I'm generally a very positive person and have been living my life with ALS in (what I think is) a very positive way. The positive here is that there is real hope for people who are just being diagnosed now, or perhaps in the next few years. Wonderful news!

-Tom
 
Re: common cause of als

I have a number of friends who are doctors.

I just sent them all the following email

"Hello my Doctor friends,

Hope you are all having a great summer.

Check out the press release below.

Major ALS Breakthrough : Northwestern University Newscenter

I would consider it a great personal favour if you would all drop everything you are doing and focus on trying to find a way to fix this ubiquilin2 malfunction.

If you could do it by Christmas that would be great.

As a special incentive, the first person who fixes this problem will receive my most prized possession. A comic book from 1971, House of Mystery issue #92 featuring the first appearance of the Swamp Thing in near mint condition.

As an added bonus on the back cover of the comic is a Daisy BB ad showing a boy devastated because it is raining and he can't set up his target practice outside. BUT WAIT! Dad has a great idea! We can set up a shooting gallery right here in the living room. Just follow these easy step by step instructions and you can turn your living room into a shooting range while little sis watches.

Keep me posted.

Thanks so much.

Richard"
 
Re: common cause of als

LOVE IT Richard!
 
Has anyone participating in a drug trial such as dexpramipexole or NP001 heard their doctors talk about whether the drugs' mechanisms agree with this new finding?
 
Re: common cause of als

I've had a number of responses from my doctor friends:

I will get right on it Richard!

Richard - throw in the x-ray glasses , 7 foot frankenstein , and family of sea monkeys and you've got a deal.

Hi Rich: I'm just a country nephrologist but I have complete confidence in Lisa figuring this out in her lab. But I do want the comic book. Cheers!

Hi Richard! It's awesome to hear from you, and AMAZING to read this paper! As you know, I'm working in the Center for Fetal Diagnosis and Treatment at the Children's Hospital of Philadelphia working on gene therapy in utero. I hereby promise to add UBQLN2 to my vector and will report back to you immediately upon getting results. You don't even have to give me the comic book, however I will insist on some cuddle time with Amelia next time I'm in town - then we can call it even.

The last response sounds promising.

That was easy! And some of you thought this would be difficult.
 
When we did Phase 1 of NP001 last year, in laymens terms, they said it was to clean out the garbage left behind in the cells, which sounds like the recycling they are talking about.
 
Re: common cause of als

Richard, If they cough up a pill for us by Christmas I'll throw in my Mom's Shirley Temple milk pitcher.
 
Re: common cause of als

I have been processing this info and reading all the news items and I must say it's pretty exciting news. I have no idea if it will help me personally but it's great to see "real" progress.
 
Re: common cause of als

Here is the actual title and summary from the article in Nature

Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia

Amyotrophic lateral sclerosis (ALS) is a paralytic and usually fatal
disorder caused by motor-neuron degeneration in the brain and
spinal cord. Most cases of ALS are sporadic but about 5–10% are
familial. Mutations in superoxide dismutase 1 (SOD1)1,2, TAR
DNA-binding protein (TARDBP, also known as TDP43)3,4 and
fused in sarcoma (FUS, also known as translocated in liposarcoma
(TLS))5,6 account for approximately 30% of classic familial ALS.
Mutations in several other genes have also been reported as rare
causes of ALS or ALS-like syndromes7–15. The causes of the remaining
cases of familial ALS and of the vast majority of sporadic ALS
are unknown. Despite extensive studies of previously identified
ALS-causing genes, the pathogenic mechanism underlying motorneuron
degeneration in ALS remains largely obscure. Dementia,
usually of the frontotemporal lobar type, may occur in some ALS
cases. It is unclear whether ALS and dementia share common
aetiology and pathogenesis in ALS/dementia. Here we show that
mutations in UBQLN2, which encodes the ubiquitin-like protein
ubiquilin 2, cause dominantly inherited, chromosome-X-linked
ALS and ALS/dementia. We describe novel ubiquilin 2 pathology
in the spinal cords of ALS cases and in the brains of ALS/dementia
cases with or withoutUBQLN2 mutations. Ubiquilin 2 is a member
of the ubiquilin family, which regulates the degradation of ubiquitinated
proteins. Functional analysis showed that mutations in
UBQLN2 lead to an impairment of protein degradation.
Therefore, our findings link abnormalities in ubiquilin 2 to defects
in the protein degradation pathway, abnormal protein aggregation
and neurodegeneration, indicating a common pathogenic mechanism
that can be exploited for therapeutic intervention.
 
Are we all going to get together and party when they discover a cure for this?
 
This is a start ... I'll take as HOPE!
 
Here is a press release from the ALS Society of Canada regarding the Northwestern research. Much like Katie and Allen, they take a more tempered view of the findings. The synopsis is pretty much identical to Katie's original comment

http://als.ca/_media/docs/Concerning ALS-related press releases of 21-22 August 2011.pdf


Synopsis: The underlying causes of most forms of ALS have not been identified. This new study has confirmed a
mechanism common to all forms of ALS, reinforcing the need to continue developing therapies related to that
mechanism. The problem is a breakdown in the recycling system for damaged proteins in specific neurons in the spinal cord and brain that results in severely damaged cells. Problems with this mechanism also likely play a role in other neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

This study is a validation of much research currently being conducted in Canada. It is a new piece of the puzzle that will help us find a treatment/cure for ALS.
 
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If I'm reading this document correctly, they have known about this mechanism for awhile, but this new finding proves it to be true definitively. Does this mean that they have been developing treatment targeting it already? Does anyone know of a treatment in development?
 
I talked to my neuro about this. Apparently this mechanism has been known for a long time and a drug came close to clinical trials a few yaers ago targeting this mechanism. However the drug was deemed unsafe and was pulled because it had some bad side effefcts on mice.
 
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