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Comment by nonbel | Hacker News Reader

>"Although the results are promising, this trial was fairly small, and as Vox points out, it’s frowned upon in the research community to change your end results midway through a trial. At the moment, the FDA requires new drugs targeting Alzheimer’s to go through two phase III trials, showing a reduction of both a biological marker for the disease and cognitive decline. In March of this year, the organization published a draft report that said in the future they would accept only a reduction of biomarkers, without a reduction in cognitive decline, a decision has been supported by the research community. This is because in early cases of Alzheimer’s, patients may have the biological indicators of the disease without actually showing symptoms."

I wouldn't consider this promising at all. It looks like it was "too hard" so standards are being lowered.

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> It looks like it was "too hard" so standards are being lowered.

Not at all. It turns out one of the standards was not relevant to the target population. As you quoted: "This is because in early cases of Alzheimer’s, patients may have the biological indicators of the disease without actually showing symptoms."

There's no point in trying to alleviate symptoms where there are no symptoms. If I develop a drug that removes tumors that eventually caused headaches, is it somehow lowering standards if it removes tumors before a headache appears?

>"This is because in early cases of Alzheimer’s, patients may have the biological indicators of the disease without actually showing symptoms."

This is called a "degenerating research programme". The theory always lags the facts, this is just another ad hoc adjustment to keep it going for some reason. Why? I really cant understand. Whats the last interesting prediction that has come out of the amyloid hypothesis?

Here is an interesting prediction: Amyloid accumulation will be found to be associated with every single disease state where it is investigated. Every single one. This is because amyloid formation is very thermodynamically favorable for polypeptide chains and a cell must be healthy to prevent it.

That's interesting. I've got a kidney infection at the moment, are you suggesting that I have amyloid plaques in my brain?

Wikipedia has a bit on it:

>"Amyloidosis is a group of diseases in which abnormal protein, known as amyloid fibrils, builds up in tissue. [...] The presentation of amyloidosis is broad and depends on the site of amyloid accumulation. The kidney and heart are the most common organs involved. [...] AA is suspected on clinical grounds in individuals with longstanding infections or inflammatory diseases." https://en.wikipedia.org/wiki/Amyloidosis

Well pretty much everyone does have some amyloid plaques in their brain but I mean that there is a higher level of amyloid in your kidney now than before you had the infection.

but arent the biological markers of Alzheimer's still theoretical? i thought that is part of why a cure is so hard to come by -- we don't know if it's the plaques or something else. so if you measure a drug that reduces plaques but you don't measure its affects on cognition how do you know you are making progress?

They've defined it circularly so that the same symptoms without extensive plaques is a different disease.

At this point, reading headlines like this, I'm just going into the comment thread expecting the top comment to tell me, why the headline is BS. And again, I was right.

Well if you have a drug to catch someone early and they have no measurable decline in cognitive ability how would you ever have a drug that prevents the disease get passed?

You compare them to a control group and check which group has had more decline after five or ten years?

yeah, i got this feeling too. the drug companies are desperate to make money off of alzheimer's, but the disease is too obstinate to go along with their wishes unless they juke the stats.

improving cognitive function is very difficult under any circumstance. making a drug that alters a biomarker reliably is, in comparison, very easy.

of course, if the biomarker doesn't have a strong correlate to health, it won't help the patient. but they would prefer to sell drugs that "work" without improving the patient's quality of life if it is between that and not selling any drugs.

the other reason that these interventions are always so focused on "early" or "preclinical" alzheimer's is because that's when the patient's brain is still more neurotypical than not. as the disease progresses, i get the feeling that many of the normal rules of thumb regarding brain function and drug action in the brain start to fall through, which makes therapy development far harder.

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