This is the clearest account of the delivery problem I've read, and the petunia opening earns its place.
Footnote 9 might be the most important sentence in the piece, and it's buried. The claim that most trials will still fail because the biology is wrong, but that the success rate conditional on correct biology should be high, is a different argument from the one the body makes. The body promises more treatments. The footnote promises interpretable failures. That second thing seems bigger. With small molecules a negative trial is ambiguous, because the chemistry and the hypothesis fail together and you can't tell which. Once delivery is solved for an organ and the chemistry is held constant, a negative result is evidence about the disease rather than about the molecule. Which makes the Alnylam and Arrowhead programs interesting beyond whether they work.
One targets the precursor, the other tau, and under your footnote's logic even a null result would say something definite about which limb of the cascade carries the disease.
A wonderful piece. Thanks for writing this up so clearly.
Incredible. Thank you for sharing this knowledge for free!
Excellent article. I actually understood it and I have no background in organic chemistry or bio medicine.
This is the clearest account of the delivery problem I've read, and the petunia opening earns its place.
Footnote 9 might be the most important sentence in the piece, and it's buried. The claim that most trials will still fail because the biology is wrong, but that the success rate conditional on correct biology should be high, is a different argument from the one the body makes. The body promises more treatments. The footnote promises interpretable failures. That second thing seems bigger. With small molecules a negative trial is ambiguous, because the chemistry and the hypothesis fail together and you can't tell which. Once delivery is solved for an organ and the chemistry is held constant, a negative result is evidence about the disease rather than about the molecule. Which makes the Alnylam and Arrowhead programs interesting beyond whether they work.
One targets the precursor, the other tau, and under your footnote's logic even a null result would say something definite about which limb of the cascade carries the disease.
Excellent. Very insightful. And the fact that more can be done - areas like Alzheimer’s look like are in target.
Apparently, nature has made last-mile delivery a tough job.
Whether in the real world or inside the body.
In space too? Landings on the moon or other planets, for example?
What is the sta6tus of stem cells and being able to regrow organs or damaged tissue, such as lung damage caused by emphysema?
What a coincidence!
I'm publishing an article on programming medicines on Saturday.
But mine has a different focus.
I'll talk about precision oncology, but you talked about RNAi.