3 ms·

Why would ultrasound removal of amyloid-B be effective while other chemical/medical treatments offering the same would not?

Krssst 2y ago
> Transgenic mice with increased amyloid-β (Aβ) production Looks to me they increased amyloid-B then removed the increase, which solved symptoms. I don't know much about this but my understanding was that Alzheimer disease had to have a bit more going on than just amyloid-B accumulation.
- resoluteteeth 2y ago
  Yes that is the major potential problem with this type of mouse model in general. Mice are modified to have a condition that resembles something like alzheimer's disease and then treatments are tested, but there's no guarantee that the underlying disease is actually the same, so if the condition that is induced in the mice is just a symptom rather than the underlying cause of the human disease, or just superficially resembles it, the treatment may not actually be effective in humans.
- rich_sasha 2y ago
  My understanding is, it's definitely true that the amyloid protein is toxic to brain tissue. It's just that targeting that tissue has not, to date, lead to a breakthrough. I suppose in principle it could be because we don't ha e good ways to remove them, and this is it.
hnuser123456 2y ago
Percussive maintenance is sometimes the most effective option.
pera 2y ago
> Anti-amyloids are expensive, and insurance won’t always cover them https://www.webmd.com/alzheimers/anti-amyloid-therapies-alzheimers https://www.webmd.com/alzheimers/anti-amyloid-therapies-alzh... > the key reason donanemab isn’t available through the NHS is its cost. The treatment is estimated to cost around £25,000 a year per patient https://theconversation.com/alzheimers-drug-approved-in-the-uk-but-it-wont-be-available-on-the-nhs-heres-why-242127 https://theconversation.com/alzheimers-drug-approved-in-the-...
- twasold 2y ago
  Insurance doesn’t cover them precisely because they don’t work. https://www.science.org/content/blog-post/does-it-work-does-it-do-harm-and-more-basic-questions https://www.science.org/content/blog-post/does-it-work-does-...
  - 0cf8612b2e1e 2y ago
    Beat me to it. Relevant Derek Lowe quote from a different article. But as I did when I wrote about the lecanemab data, let’s get some of the disclaimers out of the way at the beginning. I mentioned there that no Alzheimer’s drug candidate has ever stopped the progression of disease, and that of course means that no such candidate has ever reversed any of the damage, either. See below for more on that as it relates to donanemab, but what we’re looking for in all these cases is essentially slowing down the rate at which these patients deteriorate. … But here goes: lecanemab slowed decline by 27% on the CDR-SB scale, and donanemab slowed it by 29%. As you will can see from my earlier writeup on the former drug, opinion was very much divided on whether the lecanemab numbers would even be noticeable in real-world use (there is no standard for clinically meaningful efficacy in CDR-SB changes). So I would have to think that the same objections apply here. We cannot be sure that this drug will actually make a difference in the real-world care of patients with Alzheimer’s - not yet, anyway. This point is completely avoided in the Lilly press release, but it is nonetheless real and we will be hearing more about it from clinicians - well, if you listen closely above all the noise, that is. https://www.science.org/content/blog-post/lilly-s-new-donanemab-data-alzheimer-s https://www.science.org/content/blog-post/lilly-s-new-donane...

Krssst 2y ago

> Transgenic mice with increased amyloid-β (Aβ) production Looks to me they increased amyloid-B then removed the increase, which solved symptoms. I don't know much about this but my understanding was that Alzheimer disease had to have a bit more going on than just amyloid-B accumulation.

resoluteteeth 2y ago
Yes that is the major potential problem with this type of mouse model in general. Mice are modified to have a condition that resembles something like alzheimer's disease and then treatments are tested, but there's no guarantee that the underlying disease is actually the same, so if the condition that is induced in the mice is just a symptom rather than the underlying cause of the human disease, or just superficially resembles it, the treatment may not actually be effective in humans.
rich_sasha 2y ago
My understanding is, it's definitely true that the amyloid protein is toxic to brain tissue. It's just that targeting that tissue has not, to date, lead to a breakthrough. I suppose in principle it could be because we don't ha e good ways to remove them, and this is it.

hnuser123456 2y ago

Percussive maintenance is sometimes the most effective option.

pera 2y ago

> Anti-amyloids are expensive, and insurance won’t always cover them https://www.webmd.com/alzheimers/anti-amyloid-therapies-alzheimers https://www.webmd.com/alzheimers/anti-amyloid-therapies-alzh... > the key reason donanemab isn’t available through the NHS is its cost. The treatment is estimated to cost around £25,000 a year per patient https://theconversation.com/alzheimers-drug-approved-in-the-uk-but-it-wont-be-available-on-the-nhs-heres-why-242127 https://theconversation.com/alzheimers-drug-approved-in-the-...

twasold 2y ago
Insurance doesn’t cover them precisely because they don’t work. https://www.science.org/content/blog-post/does-it-work-does-it-do-harm-and-more-basic-questions https://www.science.org/content/blog-post/does-it-work-does-...
- 0cf8612b2e1e 2y ago
  Beat me to it. Relevant Derek Lowe quote from a different article. But as I did when I wrote about the lecanemab data, let’s get some of the disclaimers out of the way at the beginning. I mentioned there that no Alzheimer’s drug candidate has ever stopped the progression of disease, and that of course means that no such candidate has ever reversed any of the damage, either. See below for more on that as it relates to donanemab, but what we’re looking for in all these cases is essentially slowing down the rate at which these patients deteriorate. … But here goes: lecanemab slowed decline by 27% on the CDR-SB scale, and donanemab slowed it by 29%. As you will can see from my earlier writeup on the former drug, opinion was very much divided on whether the lecanemab numbers would even be noticeable in real-world use (there is no standard for clinically meaningful efficacy in CDR-SB changes). So I would have to think that the same objections apply here. We cannot be sure that this drug will actually make a difference in the real-world care of patients with Alzheimer’s - not yet, anyway. This point is completely avoided in the Lilly press release, but it is nonetheless real and we will be hearing more about it from clinicians - well, if you listen closely above all the noise, that is. https://www.science.org/content/blog-post/lilly-s-new-donanemab-data-alzheimer-s https://www.science.org/content/blog-post/lilly-s-new-donane...