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.