Conclusions
Current clinical and experimental data cumulatively suggest that it is unlikely that a “universal” ALS drug will be effective in ALS patients. In contrast, different subtypes of ALS patients will require different drug treatment strategies according to the suggested chemogenomic approach. In this direction, the use of animal models for testing drugs against a certain genetic background or the re-evaluation of already completed animal and/or clinical studies is of great importance. As elaborated here, the extrapolation of preclinical data to patients should be performed cautiously since evolutionary distant models such as drosophila and C. elegans may provide false findings regarding the efficacy of a drug, in contrast to mice. It is known that the genome and the networks of functional connectivity are significantly different between the more evolutionary distant animals and these could significantly affect the biological outcome of pharmacological treatment. Other factors should also be taken into consideration when evaluating preclinical data, e.g. in many preclinical studies, treatment was initiated before the onset of symptoms, which cannot be applied to ALS patients. Currently, diagnosis of ALS takes almost a year since it relies only on the assessment of the clinical status, the electrophysiological examination, and progressive exclusion of other pathologies. Nonetheless, the clinical benefit of riluzole is higher when administered early in the course of the disease (Zoing et al., 2006). Thus, early diagnosis will enhance therapeutic efficacy. For this, molecular diagnosis of ALS is urgently needed in clinics (Pampalakis et al., 2019). If early drug treatment is combined with patient subgrouping/stratification, it is expected to further extend the clinical benefits of the tested compounds.