Breakthrough Offers Defined Path towards ALS Treatment
ROME, ITALY – Researchers are expressing optimism regarding a newly defined therapeutic pathway for Amyotrophic Lateral Sclerosis (ALS), focusing on the role of the TDP-43 protein and its impact on messenger RNA regulation. Mario Sabatelli, clinical manager of the Nemo rome Armida barelli Center at the Gemelli Polyclinic and Aisla contact person for the Medical Scientific Commission, stated at the ‘La Promise 2025’ event hosted by Adnkronos agency, “There is a scientific basis that allows us to have optimism, for the first time we have a clear direction, a solid disease hypothesis and a potential therapeutic tool that works on exactly that mechanism.”
The research centers on the TDP-43 protein, which is altered in nearly all ALS patients. Normally located in the cell nucleus, in ALS it migrates to the cytoplasm, disrupting its function of regulating hundreds of messenger RNAs – molecules crucial for protein synthesis. Scientists are now systematically studying these RNAs to pinpoint those most critical in driving neuronal damage.
“Until now we knew it in a generic way; now we are finally understanding which RNA it regulates, by what mechanisms and what its loss from the nucleus entails,” Sabatelli explained. While acknowledging the work ahead - “it will take time, investment and a lot of work” – researchers believe identifying these key RNAs will unlock targeted interventions.
A potential therapeutic approach involves antisense oligonucleotides (ASOs), molecules capable of entering cells and correcting the fate of altered RNAs. Supporting this approach, a recent article published in Nature demonstrated the profound influence of these alterations on protein synthesis. Sabatelli concluded, “It is indeed another fundamental piece which strengthens this line of research.”
