Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in 
adults. Classical ALS is characterized by the death of upper and lower motor 
neurons leading to progressive paralysis. Approximately 10 % of ALS patients 
have familial form of the disease. Numerous different gene mutations have been 
found in familial cases of ALS, such as mutations in superoxide dismutase 1 
(SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, 
ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were 
generated to mimic the disease and to test future treatments. However, no animal 
model fully replicates the spectrum of phenotypes in the human disease and it is 
difficult to assess how a therapeutic effect in disease models can predict 
efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS 
leads to a variety of responses to similar treatment regimens. From this has 
emerged the concept of personalized medicine (PM), which is a medical scheme 
that combines study of genetic, environmental and clinical diagnostic testing, 
including biomarkers, to individualized patient care. In this perspective, we 
used subgroups of specific ALS-linked gene mutations to go through existing 
animal models and to provide a comprehensive profile of the differences and 
similarities between animal models of disease and human disease. Finally, we 
reviewed application of biomarkers and gene therapies relevant in personalized 
medicine approach. For instance, this includes viral delivering of antisense 
oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice 
models. Promising gene therapies raised possibilities for treating differently 
the major mutations in familial ALS cases.