Here's an article by Steve Perrin, at the ALS Therapy Development Institute, and you can tell that he's a pretty frustrated guy. With good reason.
That chart shows why. Those are attempted replicates of putative ALS drugs, and you can see that there's a bit of a discrepancy here and there. One problem is poorly run mouse studies, and the TDI has been trying to do something about that:
After nearly a decade of validation work, the ALS TDI introduced guidelines that should reduce the number of false positives in preclinical studies and so prevent unwarranted clinical trials. The recommendations, which pertain to other diseases too, include: rigorously assessing animals' physical and biochemical traits in terms of human disease; characterizing when disease symptoms and death occur and being alert to unexpected variation; and creating a mathematical model to aid experimental design, including how many mice must be included in a study. It is astonishing how often such straightforward steps are overlooked. It is hard to find a publication, for example, in which a preclinical animal study is backed by statistical models to minimize experimental noise.
All true, and we'd be a lot better off if such recommendations were followed more often. Crappy animal data is far worse than no animal data at all. But the other part of the problem is that the mouse models of ALS aren't very good:
. . .Mouse models expressing a mutant form of the RNA binding protein TDP43 show hallmark features of ALS: loss of motor neurons, protein aggregation and progressive muscle atrophy.
But further study of these mice revealed key differences. In patients (and in established mouse models), paralysis progresses over time. However, we did not observe this progression in TDP43-mutant mice. Measurements of gait and grip strength showed that their muscle deficits were in fact mild, and post-mortem examination found that the animals died not of progressive muscle atrophy, but of acute bowel obstruction caused by deterioration of smooth muscles in the gut. Although the existing TDP43-mutant mice may be useful for studying drugs' effects on certain disease mechanisms, a drug's ability to extend survival would most probably be irrelevant to people.
A big problem is that the recent emphasis on translational research in academia is going to land many labs right into these problems. As the rest of that Nature article shows, the ways for a mouse study to go wrong are many, various, and subtle. If you don't pay very close attention, and have people who know what to pay attention to, you could be wasting time, money, and animals to generate data that will go on to waste still more of all three. I'd strongly urge anyone doing rodent studies, and especially labs that haven't done or commissioned very many of them before, to read up on these issues in detail. It slows things down, true, and it costs money. But there are worse things.