Indeed, axon retraction, selective spinal motor neuron death, loss of innervation of motor end-plates, muscular atrophy and progressive motor deficit with terminal paralysis of hind limbs are observed in this murine model. The SOD1 G93A mice demonstrate many of the features seen in human ALS pathology and represent the most widely used in vivo model for the study of ALS. However, the discovery of causative inherited and de novo gene mutations, together with the generation of the SOD1 G93A transgenic mouse model uncovered important pathological mechanisms in ALS. The specific molecular mechanisms behind ALS onset, development and progression are not fully understood. Nevertheless, clinical variability such as rate of progression, site of onset (limb or bulbar) and survival within patients and even relatives who carry the same gene mutation highlight the importance of external factors which may play a role in the susceptibility and age of onset of the disease. SALS and FALS are clinically indistinguishable, and since mutations in FALS genes are also present in sporadic or isolated cases of ALS, the disease can be interpreted as complex and multi-factorial. More than 20 mutated genes have been found to cause FALS including SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C9orf72 and very recently TBK1. Hereditary forms of the disease (familial ALS or FALS), are predominantly autosomal dominant and rarely X-linked or recessive. ALS is mainly sporadic in origin (SALS) but a family history of the disorder can be found in ~10% of cases. Affected individuals usually die within 2 to 5 years after diagnosis due to respiratory failure. The disease typically manifests during the sixth to seventh decade of life leading to progressive muscle atrophy, weakness and paralysis. The estimated incidence of ALS across the world is 2/100,000, with a prevalence of up to 7.4/100000. However, technical hurdles such as optimal dose, differentiation state, route of administration, and the underlying potential therapeutic mechanisms still need to be assessed.Īmyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a rapidly progressive neurodegenerative condition characterized by selective degeneration of both upper motor neurons (MNs) in the motor cortex, and lower motor neurons in the brainstem and ventral horn of the spinal cord. In summary, given their high proliferation activity, immunomodulation, multi-differentiation potential, and the capacity to secrete neuroprotective factors, adult mesenchymal stem cells represent a promising candidate for clinical translation.

This review will cover publications in this field and comprehensively discuss advances, challenges and future direction regarding the therapeutic potential of stem cells in ALS, with a focus on mesenchymal stem cells.

Despite substantial improvements in stem cell technology and promising results in preclinical studies, several questions still remain unanswered, such as the identification of the most suitable and beneficial cell source, cell dose, route of delivery and therapeutic mechanisms. In several preclinical studies using the SOD1 G93A mouse model of ALS, stem cells were demonstrated to be neuroprotective, effectively delayed disease onset and extended survival. In recent years, stem cell transplantation as a new therapy for ALS patients has been extensively investigated, becoming an intense and debated field of study.

The specific molecular mechanisms underlying the disease pathology are not fully understood and neuroprotective treatment options are minimally effective. Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle atrophy, weakness, paralysis and ultimately death within 3–5 years from onset of symptoms.

Stem cell treatment for als