

Cause of ALS is found, Northwestern team says - nurik
http://www.chicagotribune.com/news/local/ct-met-northwestern-als-breakthrough-20110822,0,6531848.story

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linktylr
My dad also died of ALS last year.

Identifying the cellular mechanisms underlying ALS is crucial. At the same
time I'm disheartened by the conclusion of the researchers that this will pave
the way to the development of drugs. Why is that always the first solution we
turn to?

So ubiquilin2 is unable to repair damaged proteins in people with ALS. The
question is, why?

I can't help but believe ALS is an autoimmune disease that is caused by the
combination of genes and an environmental trigger. The fact that this
possibility isn't even mentioned in the article suggests that we have a long
way to go. Drugs, though helpful in some situations, are often merely band-
aids. Let's find the trigger!

Still, this is progress. My dad donated his body to Northwestern for research
so I can't help but be proud today.

~~~
gfodor
> Why is that always the first solution we turn to?

First, I'm sorry for your loss. I did want to point out that there's no reason
to believe that this is an either-or situation. Clearly research can progress
in all directions now in a more focused manner: further understanding the
cause of the mechanism identified, as well as attacking it directly.

~~~
linktylr
Yes, I agree. If we can develop a drug, I'm all in favor of it and this
certainly gets us closer to that goal. I'm simply arguing that the search for
a wonder drug/magic bullet always seems to overshadow so called root causes.

Noticeably absent from the tribune article (have not yet read the Nature
article) is any discussion of environmental triggers such as diet or
lifestyle.

We often jump from disease to drug without considering the causal factors.

~~~
Bud
Figuring out and treating/resolving causal factors does not generate millions
for pharmaceutical companies. Developing drugs does.

In particular, discovering environmental factors and trying to resolve those
especially does not produce reliable revenue streams for pharmaceutical firms,
and also rankles those with certain political assumptions.

~~~
evgen
Not really. The real problem is that many claimed environmental/diet factors
turn out to be statistical noise or complete bullshit when examined further.
If environment or diet plays a role then it is possible to discover how this
triggers some latent element of the genome or some existing physiological
process that gets subverted and from this discovery it is sometimes possible
to interrupt the process. If a pharmaceutical company can develop a wonderpill
that can be marketed with a basic message of "yes, we both know you are fat
and do not have the willpower/desire to stop grazing 24x7 but if you take our
pill we can block or delay the onset of type II diabetes" they will have a
very reliable revenue stream to look forward to...

~~~
linktylr
"Not really. The real problem is that many claimed environmental/diet factors
turn out to be statistical noise or complete bullshit when examined further."

No doubt this is true, especially in the case of meat and saturated fat.
Usually this is the result of bad science, typically drawing cause and effect
conclusions from epidemiological evidence (See Denise Minger's critique of The
China Study here: [http://rawfoodsos.com/2010/07/07/the-china-study-fact-or-
fal...](http://rawfoodsos.com/2010/07/07/the-china-study-fact-or-fallac/)).

The problem with "interrupting the process" is that we still don't know much
about the functioning of many (perhaps most) physiological processes.
Disrupting the body's natural processes in one area can cause problems of
equal or greater significance in other areas.

Also, studies proving the safety and effectiveness of drugs are, more often
than not, highly flawed. Studies frequently exaggerate the improvements seen,
fail to show that improvements are due to drugs, or are repeated until the
results they are looking for are achieved.

For an excellent review of the flaws of medical research see Lies, Damned
Lies, and Medical Science here:
[http://www.theatlantic.com/magazine/archive/2010/11/lies-
dam...](http://www.theatlantic.com/magazine/archive/2010/11/lies-damned-lies-
and-medical-science/8269/?single_page=true)) Here are but a few highlights:

"...much of what biomedical researchers conclude in published
studies—conclusions that doctors keep in mind when they prescribe antibiotics
or blood-pressure medication, or when they advise us to consume more fiber or
less meat, or when they recommend surgery for heart disease or back pain—is
misleading, exaggerated, and often flat-out wrong. He charges that as much as
90 percent of the published medical information that doctors rely on is
flawed."

"researchers were frequently manipulating data analyses, chasing career-
advancing findings rather than good science, and even using the peer-review
process—in which journals ask researchers to help decide which studies to
publish—to suppress opposing views."

"even if a study managed to highlight a genuine health connection to some
nutrient, you’re unlikely to benefit much from taking more of it, because we
consume thousands of nutrients that act together as a sort of network, and
changing intake of just one of them is bound to cause ripples throughout the
network that are far too complex for these studies to detect, and that may be
as likely to harm you as help you."

"Even if changing that one factor does bring on the claimed improvement,
there’s still a good chance that it won’t do you much good in the long run,
because these studies rarely go on long enough to track the decades-long
course of disease and ultimately death. Instead, they track easily measurable
health “markers” such as cholesterol levels, blood pressure, and blood-sugar
levels, and meta-experts have shown that changes in these markers often don’t
correlate as well with long-term health as we have been led to believe."

"The tests could turn up something, but they’re probably irrelevant. Just
having a good talk with the patient and getting a close history is much more
likely to tell me what’s wrong.” Of course, the doctors have all been trained
to order these tests, she notes, and doing so is a lot quicker than a long
bedside chat. They’re also trained to ply the patient with whatever drugs
might help whack any errant test numbers back into line. What they’re not
trained to do is to go back and look at the research papers that helped make
these drugs the standard of care. “When you look the papers up, you often find
the drugs didn’t even work better than a placebo."

I suppose I've strayed too far from the original topic, but I think I've made
my point.

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thedoctor
Here's the journal article in Nature:
[http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...](http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10353.html)

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niels_olson
Just finished reading the article from Nature (thanks, warech). So, they're
saying this ubiquilin 2 protein has a consistent mutation compared to the wild
type, it's found in patients with ALS, it' found in intr-neural tangles, and
they're hypothesizing that this protein may be involved in clearing misfolded
proteins. Wouldn't it be at least as likely that it is one of the misfolded
proteins targeted for clearing? I think the senior author, Seddique, is right:
this gives them a good direction to go in. But it's still a long road.

Unfortunately, we don't have many good cures for these sorts of diseases yet.
Enzyme replacement has worked to slow the progress of a couple of metabolic
diseases (to the tune of tens of thousands of dollars per treatment), but I'm
not aware of anything that can meaningfully clean the intracellular
environment of built up detrius, especially in the central nervous system.
That's a tall order. How would you do that? Intrathecal injections of a virus
to splice in a functioning copy of the gene? Viruses are not well tolerated in
the CNS, to my knowledge, eg, Herpes simplex encephalitis is lethal.

Best of luck on the quest though.

~~~
linktylr
I wonder if intermittent fasting would be an effective deterrent of ALS
through autophagy, though I highly doubt this would be of much good after the
disease takes hold.

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warech
This is a link to the full text: [http://extremelongevity.net/wp-
content/uploads/als_discovery...](http://extremelongevity.net/wp-
content/uploads/als_discovery.pdf)

I'm hesitant to put too much hope in this discovery. I would expect a
discovery of this magnitude to be published as a full article in Nature,
rather than a Nature Letter. I'm not sure of the difference in the publishing
process for the two, but Letters generally come across a bit rushed and are
less exhaustive than published articles (citation needed).

~~~
avalind
The difference between letters and full articles is described here [1]. I
don't think that one should view the length of the paper or whether it's
published as a Letter or an article as a marker for its scientific importance.

For instance, The paper that Watson & Crick published that described the
structure of DNA was only slightly longer than a single page [2].

[1]
[http://www.nature.com/nature/authors/gta/2a_Manuscript_forma...](http://www.nature.com/nature/authors/gta/2a_Manuscript_formatting.pdf)
[2] <http://www.nature.com/nature/dna50/watsoncrick.pdf>

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bhousel
If it turns out to be true, this guy deserves a Nobel Prize in medicine.

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gmac
For those who come to the comments before the article, ALS means amyotrophic
lateral sclerosisis or Lou Gehrig's disease, and "is a paralytic and usually
fatal disorder caused by motor-neuron degeneration in the brain and spinal
cord".

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ams6110
My mother died of ALS; this is encouraging news. Of course it's not a
treatment, yet, but given that nothing else so far has really been effective,
it's a promising discovery.

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dirtyaura
As my dad died of familial ALS last year, thus this is fantastic news to me.
And of all places, I learn this information from HN first. Thanks HN!

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rms
There's been lots of good news in medicine lately. Here's to a decade filled
with great scientific advances.

~~~
rquantz
A decade ago there were promises of huge advances in treating diseases based
on knowledge related to the human genome project, but then gene therapy kind
of fizzled out. I'm wondering if all the latest medical breakthrough news is
just the latest round of similarly overhyped findings, or if this is something
else.

Specifically, now that basic gene replacement -- perhaps we could call that a
naive application of the new genetic knowledge -- has generally been ruled
out, scientists have been looking for more subtle ways of applying what they
learned in the last two decades wrt genetics/molecular biology and it is
starting to bear fruit. INAD, but if anyone has insight into whether this
describes what has been happening lately, I'm curious to hear.

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davidgreen24
Never more proud to be a Northwestern alum. Go Cats!

