A recent publication of the results of a clinical trial of minocycline in 412 
ALS patient has aroused considerable controversy in the ALS scientific 
community. As on previous occasions, the results obtained in the laboratory are 
not reproduced in clinical practice. The reasons for this new disappointment in 
translational medicine are analysed by applying the successes obtained in the 
experimental animal model for ALS to humans. The most frequently suggested 
causes for explaining these continuous failures are unawareness of the correct 
dosage to be used, the ideal duration of the clinical trial in phase III, sample 
size, the search for a primary outcome for measurement other than survival, the 
need for biomarkers giving information on the progression of the disease and 
whether this is modified by the introduction of the drug for study. Debate 
focuses on whether the transgenic mouse model of ALS which expresses SOD1 
mutations which we have been using for more than a decade is an exact reflection 
of the clinical profile and the physiopathogenic mechanisms present in patients 
with spo- radic ALS. There is the possibility that depending on the dose 
administered, minocycline can be a neuroprotector or a neurotoxin. In other 
words, at a dose of 200 mg/day, this drug behaves like <<Dr. Jekyll>> and like 
<<Mr. Hyde>> at doses of 400 mg. For the authors of the trial, this possibility 
does not seem to be the cause of the disappointing results obtained. However, 
they acknowledge that one of the limitations of their study was that it was 
impossible to compare the effects of minocycline in the patient after receiving 
200 or 400 mg. For many other researchers running ongoing clinical trials in 
both ALS and other neurological diseases, the dose of 200 mg/day is chosen as 
ideal for testing the effectiveness of minocycline in patients. The strategy of 
administering the maximum dose of a drug to be tested may give rise to 
misleading results. We agree with the opinion of other authors, who say that 
minocycline should be given a second chance.