the ALS has fewer secrets

Two discoveries, spread within hours of each other, can lead to a breakthrough in the understanding, diagnosis and treatment of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as frontotemporal dementia (the most common form of early-onset dementia after Alzheimer’s). Nature has just published a study that reveals, for the first time, the structure of the protein associated with ALS (it is called “Tdp-43”). The discovery is due to the scientists of the Laboratory of molecular biology del Medical Research Council (Mrc) of Cambridge (United Kingdom), led by Benjamin Ryskeldi-Falcon, and two Japanese institutes: the Tokyo Metropolitan Institute of Medical Science and theAichi Medical University.

ALS, the authors explain, is the most common form of adult-onset motor neuron disease and is characterized by the deterioration of neurons responsible for controlling voluntary muscle movements. There are no effective cures or treatments to reverse the progression of the disease which, in Italy, affects about 6,000 people. However, it is known that the abnormal aggregation of the Tdp-43 protein represents the “spy” of ALS and frontotemporal dementia. The team of researchers was able to reconstruct the molecular structure of the Tdp-43 aggregates, discovering ‘unique characteristics that could explain why current diagnostic compounds based on analogous proteins associated with other neurodegenerative diseases do not appear to manifest in ALS’. Now that “we know the structure of the protein – says Ryskeldi-Falcon -, we could develop new diagnostic strategies”. These results, comments Jo Latimer, head of the Neurosciences and Mental Health Department of the MRC, «represent an important contribution to the understanding of ALS and related neurodegenerative diseases. The cause of ALS is unclear but understanding Tdp-43 will redefine the way science thinks about disease progression and potentially could lead to the development of new diagnostic and therapeutic approaches. “

Another research supported by institutions around the world, and led byUniversity of Utrecht (Netherlands), with the contribution of Italian scientists, it has instead led to the identification of 7 gene variants associated with ALS, hitherto unknown. The study, published in Nature Genetics, examined the DNA of 29,612 patients with ALS, and 122,656 healthy people, identifying 15 variants of the disease but also related to neurodegenerative processes of other pathologies. “Eight had already been identified previously, 7 are new and help to better delineate the specific neurodegeneration mechanisms of the disease”, highlights Vincenzo Silani, professor of neurology at the State University of Milan, head of Auxologico San Luca in Milan, which supported the research together with the same university and the “Centro Dino Ferrari”. “The study – adds Silani – suggests that the neurodegenerative process in ALS is originally borne by neuronal cells and not by microglial or astrocytic cells”. Furthermore, «the sharing of pathogenetic genes reported with other neurodegenerative diseases is very interesting», including Alzheimer’s and Parkinson’s. The neurologist also anticipated the result of a forthcoming work which shows that “high cholesterol levels seem to play a causal role for ALS”.