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.
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.
But we must put our strategist hats on, and think strategically.
Sure, perhaps ALS has an environmental trigger. How shall we look for it? ALS is a rare disease. There are 5600 new cases of ALS in the USA every year, out of 307 million Americans. This implies, very roughly speaking, that in a study group of 50,000 people, one person will get diagnosed with ALS every year on average. So doing a prospective study of ALS patients is going to be astonishingly expensive: You'll need to sign up hundreds of thousands of subjects, then follow them for years, to get any meaningful number of actual cases among your study participants.
The alternative is to carefully quiz ALS patients and their families after diagnosis and see if they all tend to report similar, distinct, unusual patterns in their earlier lifestyles. But self-reporting is a lousy way to look for subtle effects, especially when the sample size is necessarily small. People have spent decades trying to positively identify environmental triggers for much more common conditions, often with little result.
So if we must identify and eliminate an environmental factor before we can reduce the incidence of ALS, we probably won't reduce the incidence of ALS anytime soon. Trying to improve or extend the lives of ALS patients post-diagnosis is, perhaps, a more tractable strategy. We know exactly who to run the tests on. And I imagine that ALS patients are among the most eager volunteers for experimental treatments.
> 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.
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.
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.
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...
"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...).
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.
"...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.
On the bright side, if we assume that developing a drug (i.e. treating the symptoms) is easier than developing a 'fix' for the root cause (if the root is genetic- we don't have a long track record of fixing your genes) then we can possibly surmise that the drug is still a good thing, because at the very least it buys time for the afflicted until a root fix is found.
Under certain circumstances I believe this to be true, drugs will be a net positive (HIV comes to mind). However, we know that in most cases genes are not your destiny, it is the combination of genes and environmental triggers (such as diet, lifestyle, pollution, etc.) that cause disease.
To the extent that we encourage people to believe that their actions are meaningless we actually increase the problem by enabling a feeling of helplessness and despair that causes people to put all their faith into a "cure", whether that be some kind of drug to manage the symptoms or gene therapy. Why bother eating healthy when I can simply take this pill?
We also have a mistaken assumption that drugs are somehow perfect solutions when in many cases the cure is worse than the disease (statins come to mind). Combine known side effects with the fact that the research behind the safety and effectiveness of drugs is distorted by the media, manipulated by the drug companies, and ignored by the doctors and what we have is far from a solution to our problems.
You are right that we don't have a long track record of fixing genes (or curing chronic illness) and this should cause us to be humble about what science and technology can achieve. We must acknowledge the potential of science and technology, and thus push the limits of what we are capable of, while being aware of it's limitations, and behaving accordingly.
Skepticism should not become nihilism, nor should science become a religion.
Excepting prions, I'm not aware of any environmental factors changing a protein's function.
edit: regarding your comment below, the evidence in the Nature paper is fairly strongly in favor of a conformational change, though its all circumstantial evidence until they have a crystal structure.
I'm a doc, I'm all about environment influencing disease. I was primarily responding to what seemed to be an overly environmental view on your part. This article puts sime non-trivial evidence in the genetics camp.
Not to step on your toes glasner, as it is an easy mistake to make, but match type DOES NOT affect quality score. All keywords on phrase and broad match are judged ONLY on instances in which the search query precisely matches the keyword, regardless of match type. This is referred to as the exact match subset.
I didn't mean to imply that changing the match type will magically increase quality score. To me breaking them out as exact matches is about making the targeting better, both for the text ad and the landing page, which sets you up for a better quality score.
Because Boulder Startup Week is the poor man's SXSW and after leaving my job in September to go freelance and doing my taxes in April, I just realized that I'm a poor man.
