Biomarkers for ALS diagnosis and a treat

Manuel Portero

Biomedical Research Institute of Lleida Fundació Dr. Pifarré (IRBLleida), Spain

Every day, three new cases of amyotrophic lateral sclerosis (ALS) are diagnosed in Spain, a neurodegenerative disease that currently has an average life expectancy of less than five years from diagnosis. There is still no effective treatment and diagnosing the disease is also challenging. It takes a year to confirm the diagnosis, which delays the administration of drugs that could slow down progression of the disease.

It has been demonstrated that the use of a new drug, called Tofersen – an antisense oligonucleotide targeting the messenger RNA of the SOD1 gene, a mutated gene linked to the development of the disease – can slow its progression. However, only 2 % of ALS patients have this mutation. In this project, researchers will develop a therapy based on this type of oligonucleotide to target another altered protein, TDP-43, which will have a greater impact because it is potentially applicable to 97 % of patients who show changes related to this protein. They will conduct a preclinical study using mouse models of ALS to assess the effectiveness of the treatment and its potential toxicity, an essential step before moving to clinical trials in humans.

Building on previous work, they will also try to develop a tool to detect patients with functionally altered TDP-43, based on the presence of specific biomarkers in the cerebrospinal fluid and blood. This tool could be used for diagnostic purposes and to monitor the patient’s response to treatment, which will enable better therapeutic decisions to be made.

Targeting cryptic exons as biomarkers and ALS therapy

Stage 1