Exciting discoveries in ALS research
A recent breakthrough study led by researchers at the Technical University of Munich (TUM) has shed new light on the mysterious and often fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS). This research has uncovered crucial insights into the disease's molecular mechanisms, revealing four distinct subtypes of ALS and significant differences between male and female patients. These findings are paving the way for more personalized and potentially effective treatments for ALS.
The mystery of ALS unveiled
ALS is known for causing patients to lose control of their motor functions progressively, but the exact molecular processes behind this are still not fully understood. Previous research only scratched the surface, focusing on individual aspects of these processes. The team at TUM, led by neurologist Prof. Paul Lingor, took a comprehensive "multi-omics" approach, examining various RNA molecules and proteins to map out the disease's complexities.
Four subtypes identified
One of the most significant discoveries is that ALS can be categorized into four different subtypes. Prof. Lingor explains that while these subtypes cannot be distinguished based on clinical symptoms alone, they show distinct molecular differences. This means that treatments which may be ineffective for one subtype could be beneficial for another. For example, genes linked to inflammation and immune responses are affected in one subtype, while another subtype shows disruptions in DNA transcription into RNA molecules. Two other subtypes exhibit different signs of oxidative stress in cells.
This revelation suggests that ALS subtypes might change as the disease progresses, adding another layer of complexity to its treatment.
Gender differences in ALS
The study also highlighted notable gender differences in ALS. Men are about 1.2 times more likely to develop ALS than women, and the molecular processes differ significantly between the sexes. While the four subtypes occur equally in both men and women, men show a higher number of altered gene products. This suggests that future treatments might need to be tailored differently for men and women to be effective.
A promising new drug target
One of the most exciting findings from this study is the identification of a signaling pathway known as MAPK, which could be a prime target for new ALS drugs. Prof. Stefan Bonn, co-author of the study, suggests that repurposing an existing cancer drug that affects the MAPK pathway could be a promising approach for treating ALS.
Looking ahead: towards personalised treatment
This groundbreaking study used tissue samples from deceased ALS patients and mouse models, but the researchers are now focused on finding ways to determine ALS subtypes in living patients. Prof. Lingor emphasizes the importance of this next step, stating, "We believe that our study made an important contribution to the search for causes and therapies for ALS. Our findings have brought us a good deal closer to a more personalized and, therefore, more effective therapy."
This research marks a significant stride in the battle against ALS, offering new hope for patients and paving the way for future studies that could lead to more targeted and effective treatments.
Publication details
For those interested in the scientific details, the study is published in Nature Communications: Caldi Gomes, L., Hänzelmann, S., Hausmann, F. et al. “Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target”. Nat Commun 15, 4893 (2024). DOI:10.1038/s41467-024-49196-y
Also read: a breakthrough on age-related disease
