Author: Josu Galarza
Scientists from around the world have collaborated on a genetic study that aims to identify small changes in the genome that may be linked to the clinical development and age of onset of sporadic Creutzfeldt-Jakob disease (sCJD).
Prion diseases are classified as rare diseases due to their low incidence in the population, affecting approximately 1-2 persons per million per year. Regarding the aetiology of these conditions, i.e. the cause of the disease, it is noted that the vast majority (about 90% of cases) have no obvious origin; they are neither acquired infections nor associated with known genetic mutations. They are called sporadic because of their frequency of occurrence, but also idiopathic because of their unknown origin, and so far, impossible to predict.
Considering these data, an international group of scientists has decided to delve deeper into the genome of SCJD patients in search of genetic variations, commonly known as mutations, although this term is not the preferred one in the scientific community due to its connotations. Specifically, the research has focused on looking for small genetic changes that influence the age of onset of the first symptoms of the disease and the duration of clinical development until the patient's death.
The results of this work confirm the findings of previous studies. The authors state that the amino acid at position 129 of the prion protein appears to be of particular importance in the development of symptoms. In addition, 52 other amino acids have been identified that may be altered and could influence this aspect, although with less relevance than amino acid 129. On the other hand, no strong relationships have been found between these small variations and the age of onset of sCJD. However, the slight impact of the HS6ST3 gene as a modulator of disease onset is described. This gene is responsible for adding negative charges to certain macrosugars that make up the brain's extracellular matrix, i.e. the "mesh" that forms the filling between neurons. Although weak, this detection of HS6ST3 as a modulator of disease onset seems of particular interest, as numerous scientific articles highlight the importance of negatively charged molecules in inducing the abnormal folding of the prion protein.
Finally, the researchers analysed the genes that regulate prion protein expression, which results in a higher or lower amount of prion protein in the brain. No relationships were found between the genes that regulate the amount of prion protein and the age of onset or clinical duration of the disease. However, the authors stress the potential usefulness of therapies that reduce the amount of prion protein, as has been demonstrated in animal models.