Why Drugs That Work in Mice Don't Work in Humans • Hacker News Board

Re: Why Drugs That Work in Mice Don't Work in Humans

#111

Post by ramraj07 » Thu, Feb 28, 2019, 10:50 PM UTC

fredophile wrote: post #71

ramraj07 wrote: post #60

Earlier quoted context omitted.

14% is bad when you consider that the NEXT step after preclinical experiments is basically clinical trials (and Phase I is not to test efficacy ) which effectively costs several hundred millions of dollars or more. And the pharmas would just add the cost of 86% failed trials to the other meds that do pass, so they effectively pass the cost of their bad decisions to us. I worked in a lab that studies antibody therapeu…

I've always assumed that the reason for the low rate of success at that stage was just a result of things that work on rats not working on humans. Your post is suggesting that there is some evidence available before testing on people that would help increase this rate but gets ignored. I haven't seen anyone express this view before and would like to learn more about it. Would you please elaborate on what kind of info…

I would very much say that if the scientists and stakeholders really, really wanted to pore through the data to understand whether it might work or not, they can get some more insight from their experiments.

Most antibody therapies (which form the bulk of currently explored therapies) have to be tested on modified mice models simply because of the fact that these antibodies are raised against human targets that have to be engineered into the mice. But then such artificial models make lots of complications in their interpretation which people have to spend lots of time interpreting. I've seen on several occasions from just published data that there were glaring warning signs that a potential therapy might have adverse interactions with the immune system or such, and the company would just go ahead with trials anyway.

Re: Why Drugs That Work in Mice Don't Work in Humans

#112

Post by Pfhreak » Thu, Feb 28, 2019, 11:59 PM UTC

danieltillett wrote: post #107

Pfhreak wrote: post #76

Earlier quoted context omitted.

I find this attitude astonishing. My pets are members of my family, and I'd generally rail against experimenting on my family.

Would you let your child participate in a clinical trial if they had a disease for which there was no good treatment? Pets suffer from most of the diseases humans suffer from (cancer, heart disease, diabetes, etc) and they also have no good treatment options. We should be using these sick pets in trials to find new cures for pets and humans.

Maybe you weren't clear or I misread you. I understood you to be saying that pets were generally not being used to their potential. (E.g. perfectly healthy pets could be used as research subjects, because they aren't doing anything else valuable at the moment..)

Re: Why Drugs That Work in Mice Don't Work in Humans

#113

Post by danieltillett » Fri, Mar 01, 2019, 3:09 AM UTC

Pfhreak wrote: post #112

danieltillett wrote: post #107

Earlier quoted context omitted.

Would you let your child participate in a clinical trial if they had a disease for which there was no good treatment? Pets suffer from most of the diseases humans suffer from (cancer, heart disease, diabetes, etc) and they also have no good treatment options. We should be using these sick pets in trials to find new cures for pets and humans.

Maybe you weren't clear or I misread you. I understood you to be saying that pets were generally not being used to their potential. (E.g. perfectly healthy pets could be used as research subjects, because they aren't doing anything else valuable at the moment..)

Of course not. No one would think experimenting on healthy pets would be reasonable or ethical, but not using our sick pets to help other pets and humans is a huge waste.

Re: Why Drugs That Work in Mice Don't Work in Humans

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Post by Amygaz » Fri, Mar 01, 2019, 4:03 AM UTC

DanBC wrote: post #101

busyant wrote: post #99

Earlier quoted context omitted.

I am not the parent, but I worked at a few biotech startups. My impression is that you are _mostly_ correct (a lot of animal models for disease don't accurately reflect the analogous state in humans). However, I was privy to a situation similar to that described by the person to whom you replied. * A start-up that I worked at developed a "candidate drug" to treat a condition (I don't want to get too detailed). * The…

Imagine a similar situation but where people died: Who's corporately responsible for that decision? The company, or the individual directors? How about the NEDs?

No one. Look up Juno Therapeutic. Their trials killed more people than they saved

Re: Why Drugs That Work in Mice Don't Work in Humans

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Post by anitil » Fri, Mar 01, 2019, 4:18 AM UTC

Amorymeltzer wrote: post #94

My go-to example is Vitamin C: it's an essential nutrient for humans, but mice, like most other animals, are capable of simply producing it. That's usually a good starting point for the "they're really different" conversation.

For the curious: https://en.wikipedia.org/wiki/L-gulonolactone_oxidase#Conseq...

I couldn't really make sense of the two proposed theories, other than one suggested perhaps it was an advantageous adaption in the presence of malaria.

Re: Why Drugs That Work in Mice Don't Work in Humans

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Post by bayesian_horse » Fri, Mar 01, 2019, 7:23 AM UTC

Amygaz wrote: post #38

klmr wrote: post #22

Earlier quoted context omitted.

Absolutely. My phrasing wasn’t clear, I was contrasting organoids with the cell cultures mentioned in your reply, not with in vitro studies in general.

Organoids, organ-on-chip, 3D cell cultures, have all shown to be equivalent to each other, and better than standard 2D cell culture. Ultimately they are not very complex, definitely more than a monoculture, but no where near an organism that evolved from a single cell. They haven’t shown to be a good proxy for a whole organism. On term of disease model, they are typically artificial in the sense that genetically engi…

In-vitro and In-silico modelling might be of great use is for known problems that come up for candidate drugs in the early clinical phase: Interaction with receptors (blood/brain barrier, QT prolongation etc) or liver proteins or the like.

Of course, we are talking about the fruits on the drug tree which are potentially reachable by singular small molecule drugs.