
Biotech Company's Pig Vaccine Leads to New Alzheimer's Approach - todd8
https://www.bloombergquint.com/businessweek/united-neuroscience-s-alzheimer-vaccine-just-might-work#gs.vnXZjohD
======
nonbel
>"The patients demonstrated improved brain function and showed a reduction in
the protein plaque gumming up their neurons, the company’s report says."

Still chasing the amyloid hypothesis I see. This is a symptom, not a cause, so
they are wasting their time (in terms of actually helping the patients,
eventually someone will randomly get "positive" results and a bunch of money
if enough trials are run).

1) Up to 30% of cognitively normal elderly have detectable amyloid deposits:
[https://news.ycombinator.com/item?id=17444214#17453147](https://news.ycombinator.com/item?id=17444214#17453147)

2) Only 70% of dementia patients have detectable amyloid deposits:
[https://news.ycombinator.com/item?id=17444214#17445337](https://news.ycombinator.com/item?id=17444214#17445337)

3) Amyloid-related genetics can only account for < 10% of Alzheimer's cases:
[https://news.ycombinator.com/item?id=17444214#17457198](https://news.ycombinator.com/item?id=17444214#17457198)

4) Amyloids are the most thermodynamically favorable structure that
polypeptides can form (ie require constant vigilance by the cell to prevent):
[https://news.ycombinator.com/item?id=14914528#14917057](https://news.ycombinator.com/item?id=14914528#14917057)

5) Can anyone find a disease state where they looked for amyloids and didn't
find a positive correlation? I doubt it.

~~~
SamBam
> The patients demonstrated improved brain function

If this part of the quote is actually true, then what you are saying is either
wrong or irrelevant. They appear to have evidence it is true, and are
continuing to verify it.

There are various ways this could be helping (if it is):

1\. The amyloids are a cause of Alzheimer's

2\. The amyloids are a symptom of Alzheimer's, but are a cause of the memory
impairments

3\. The drug has a side-effect which helps the memory impairments.

In any case, what is your expertise? I love random comments that say that
scientists who have spent decades in a field are simply "wasting their time"
because they haven't read some article that was posed on the web. (NB, this
may not be the case with you, if you are indeed an expert in the field.)

~~~
jcranmer
It's a Phase II trial, which means it is focused on identifying dosage ranges
and side effects in human rather than a large-scale efficacy trial. (It's also
the first time you actually give a drug candidate to humans).

You also forgot that there is a fourth point: there is no actual effect, and
the apparent effect is statistical fluke.

It's hard to understand what could be going on from this article alone,
because it spends a whopping 1.5 paragraphs on explaining any details about
the putative vaccine. The rest of the piece reads as a generic PR fluff piece,
which makes me think that this was largely based on company-provided PR and so
anything approaching details is based on the most positive light that they can
be spun into.

~~~
gumby
> ... a Phase II trial, which means it is focused on identifying dosage ranges
> and side effects in human rather than a large-scale efficacy trial. (It's
> also the first time you actually give a drug candidate to humans).

FWIW your drug candidate is administered in all phases. Phase I you look for
side effects ("safety and tolerability"). Phase II is, as you say, a dose
ranging study, but you can't exceed dosages you've already tested for safety.
You usually have multiple arms (a placebo and a couple of dosages); when you
find an seemingly efficacious dose you then proceed to a Phase III where you
test that dosage (or several) on a statistically representative enough sample
to hopefully predict results in the population at large.

(former drug designer who has designed some Phase I and II studies).

==

Fun fact: when you file your IND with the FDA to test a new drug you aren't
actually asking for permission. You're asking them to tell you that if you
follow the protocol you have sent them, based on the evidence you've sent them
from what you know already, they won't prosecute you for violating the law on
administering unapproved drugs. Section 505 for the food and drug law has a
bunch of exceptions -- you ask then to tell you you fit in one of the
exceptions.

And if they don't tell you "no" in a 30 days...you can go ahead! I wonder if
the shutdown extends that 30 days.

~~~
jcranmer
Thanks for the correction. I thought Phase I was a pre-human clinical trial
for safety, rather than a human clinical trial. I appear to have been
mistaken.

~~~
gumby
No problem. Preclinical work is indeed called preclinical work :-).

Typically you do a bunch of _in vitro_ and _in vivo_ studies when developing
your drug candidate. When you're ready to file the IND (asking permission to
test on humans) you do a different set of studies specifically to generate the
data you need for your submission. Sometimes the agency will even tell you
where its concerns may lie so you might use a specific animal or specific test
to address them. You also include a lot of in vitro work about how you
manufacture (and control the mfg of) your test product.

The difference might be that you take and process a lot of samples in your R&D
stage, and then when you prepare your submission you get independent labs to
do the work (to show the agency you don't have your "finger on the pan" so to
speak). For example on a depot-injectable drug I worked on we did six
experiment sites per guinea pig (because we knew tissue diffusion would be
only a few millimeters) which saved us time and a lot of money but when
preparing for the FDA we did only one per, so we could guarantee to them that
_any_ trace of drug found anywhere in the tissue came from a single injection.
Likewise we did a lot of pathology ourselves just peering through the
microscope (and learned a lot!), but for the FDA we had the animal lab send
tissue samples directly to an external pathologist who then sent us a report
without any input from us. Etc.

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devereaux
> Although the small number of patients prevents United from drawing any major
> statistical conclusions

A small number of patients only prevent drawing major statistical conclusion
if the effect is too small compared to the size of the group.

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SubiculumCode
Anyone have a link to the clinical trial?

------
e40
Can't read with uBlock Origin default settings. Text is fuzzed.

~~~
theandrewbailey

        .blur-container {
            filter: blur(5px);
        }
    

Who thought that was a good idea?

Defeated by reader mode.

~~~
eikenberry
I always forget about reader mode. I'll try to remember it more in the future.
It let me read this site without having to worry about enabling javascript or
dancing around ad-blocker issues.

