There is no scientific explanation for this phenomena. It is not even recognized as a problem.
In addition drug research on chronic diseases in mice translates rarely in humans. The cost is enormous for the society, again there is no explanation, and little motivation to improve this dire situation.
We must miss something huge.
I would discuss this on a philosophical level, particularly how we think about disease and health, and how it has straight consequences on the design of clinical trials.
In my understanding the notion that a drug should have effects in a few days or at least a few weeks, is deeply associated with communicable diseases. In our young age, we had fevers and in a few days it was all gone and we were back at the playground with as much energy as before.
Health is perceived as the "normal" situation.
Doctors have the same mindset: They want you to keep your blood work in the standardized values, specialists search for "anomalies" with imaging technologies.
For everyone in our societies health is the norm and diseases are only temporary deviations.
I argue that diseases are not temporary deviation to the norm.
Our bodies are constantly changing, even during illness, and there is no way to get healthy quickly. We lose capacities, organs atrophy or remodel. It is therefore unlikely that a return to health will be rapid.
Intuitively if you've had an illness for a few years, it will probably take a few years for you to regain your health. There is no magic pill, and it is a dangerous odyssey.
This why drugs work in mice and apparently not humans. When a mice model of disease heals in a month, the equivalent duration for humans is 3 years. No clinical trial tests drugs more than 6 months on the same patient.
This has dire consequences: As most clinical trials for chronic diseases last only a few months, they indeed fail to discover any significant improvement and we see that.
One way to improve this situation would be to change the goals of phases III and IV.
Phase III should have two goals: - Detect at least a minimal improvement in health. - Make sure the drug has nearly no side effects. Today side effects are minimized in clinical trials if there is no efficacious drugs. The idea is roughly that whatever improves the situation is desirable. This is perfectly correct if the uncomfortable time last only a few days, it is unacceptable if the side effects must be endured decades.
Phase IV should verify that the drug is indeed fully effective after a few years.
This book retraces the main achievements of ALS research over the last 30 years, presents the drugs under clinical trial, as well as ongoing research on future treatments likely to be able stop the disease in a few years and to provide a complete cure in a decade or two.