Moving toward a predictive and personalized clinical approach in amyotrophic lateral sclerosis: novel developments and future directions in diagnosis, genetics, pathogenesis and therapies

Abstract

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that affects upper and lower motor neurons in the brain and spinal cord, with progressive weakness and atrophy of most muscles in the body and is almost always fatal within 3-5 years. A small proportion of cases are familial, and remarkable achievements have been made during the last years in understanding the genetics of the disease. In spite of this, the basic pathogenic mechanisms underlying the sporadic disease are still poorly understood. There is urgent need for better understanding of the pathogenic processes in order to be able to develop effective treatments. The present review will focus on recent knowledge gained in diagnosis, genetics, pathogenesis and therapies in ALS. Future development of diagnostic technologies integrating genetic, environmental and individual information will enable us to predict a population at risk for ALS. New treatments actually in development will help improve the medical management of ALS patients, taking into consideration individual traits, as genetic background, and pave a way for a more effective personalized diagnostic and treatment approach.

Fig. 1

Atrophy of thenar eminence and weakness of finger extensors, more prominent on the right, in a 70-years-old woman with symptoms of ALS for 6 months

Fig. 2

This 40-years-old patient is completely paralyzed and mechanically ventilated. He chooses letters on a computer screen with light beams refracted by his eye balls. He wrote in this way (in hebrew on the top of the screen): “I am completely paralyzed, there is no single part of my body that I can move”