Management of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease caused by the degeneration of motor neurons. We report a case of a 45-years-old patient with ALS to underline difficulties and challenges in ALS management. Even though ALS remains fatal, several advances have been made in improving the consequences of this disease: symptomatic treatments have an important role in controlling sialorrhea, bronchial secretions, pseudobulbar emotional lability, cramps, spasticity, depression and anxiety, insomnia and pain. An adequate management of ALS should be multidisciplinar, involving not only the neurologist, but also family physicians and many other specialists, such as pulmonologist, rehabilitation medicine physician, speech therapist, dietitian and psychologist. The multidisciplinary approach should be aimed at relieving specific problems associated with the disability of single patients and improving their quality of life

ALS mutant FUS proteins are recruited into stress granules in induced pluripotent stem cells- derived motoneurons

Patient-derived induced Pluripotent Stem Cells (iPSCs) provide an opportunity to study human diseases mainly in those cases where no suitable model systems are available. Here we have taken advantage of in vitro iPSCs derived from patients affected by Amyotrophic Lateral Sclerosis and carrying mutations in the RNA-binding proteins FUS to study the cellular behavior of the mutant proteins in the appropriate genetic background. Moreover, the ability to differentiate iPSCs into spinal cord neural cells provides an in vitro model mimicking the physiological conditions. iPSCs were derived from FUS(R514S) and FUS(R521C) patients' fibroblasts, while in the case of the severe FUS(P525L) mutation, where fibroblasts were not available, a heterozygous and a homozygous iPSC lines were raised by TALEN-directed mutagenesis. We show that aberrant localization and recruitment of FUS into stress granules (SGs) is a prerogative of the FUS mutant proteins and occurs only upon induction of stress in both undifferentiated iPSCs and spinal cord neural cells. Moreover, we show that the incorporation into SGs is proportional to the amount of cytoplasmic FUS, nicely correlating with the cytoplasmic delocalization phenotype of the different mutants. Therefore, the available iPSCs represent a very powerful system for understanding the correlation between FUS mutations, the molecular mechanisms of SG formation and ALS ethiopathogenesis