David Pozo Pérez
Professor of Biochemistry and Molecular Biology at the University of Seville, principal investigator at CABIMER (CSIC-US) in the Laboratory of Cellular and Molecular Neuroimmunology
Research led by a team at Case Western Reserve University in Cleveland, Ohio, has identified the molecular effects of the P56S mutation on motor neuron function. They link this effect to inadequate responses of neurons to a stressful environment in which interactions between the mitochondria and the endoplasmic reticulum may play a significant role. This mutation is related to a rare subtype of ALS, called ALS Type VIII, which is characterised by its early onset (in the thirties) and very slow progression of motor impairment.
The work is important because it identifies mechanisms of action, which is essential for establishing rational strategies for pharmacological intervention. There are several limitations in terms of translating the results. The most important is that all the results were obtained in vitro and, therefore, the contribution of other cell types to the onset and establishment of this type of ALS is not contextualised. The absence of preclinical studies in humanised models would be of great added value. Molecular studies that help us understand how neurons manage stressful situations are essential, although we still do not know the origin, dynamics and effects of the causes that generate these situations.
If we know anything about the pathological mechanisms of ALS, it is that it is not a single entity and that dialogue between different cell types is essential to understanding it and, therefore, to managing it clinically in the future.