- Genetic research is enabling the development of therapies for certain ALS patients.
- Treatments such as tofersen have shown that identifying certain genetic alterations can have direct therapeutic implications.
24.06.2026
Amyotrophic lateral sclerosis is a complex disease. Approximately 90% of cases are not inherited, and the exact cause of the disease is unknown. However, it is known that essential cellular processes fail in motor neurons as a result of a combination of biological, genetic, and environmental factors.
Although hereditary cases are the least common, genetics provides clues about the disease in many patients, as certain alterations are also present in cases with no family history. “In most patients with familial ALS, genetic variants associated with Mendelian forms are identified. This accounts for 50–85% of patients with a family history. But we also find these variants in 10%–20% of cases with no family history,” explains Dr. Alba Navarro, Head of Neurology at Health in Code.
For years, determining whether an ALS patient carried genetic variants associated with the disease served to confirm the diagnosis, guide patient follow-up, and provide family genetic counseling. Now, genetic information also facilitates access to therapeutic options. Targeted therapies such as tofersen, funded in Spain, have shown benefits in patients with variants in the SOD1 gene.
Why a treatment for a small number of patients can benefit many more
Between 2% and 3% of ALS patients have this genetic form of the disease associated with SOD1. Although the proportion of patients who can benefit from this therapy is relatively small, the discovery of its effectiveness contributes greatly to ALS research. It is proof that it is possible to act on a specific molecular mechanism and slow neuronal damage.
Genetics no longer only helps us understand ALS; it is beginning to determine which patients may benefit from targeted therapies and clinical trials.
In the results of the VALOR study, which supported the approval of tofersen (Qalsody), improvements in function and strength have been observed in patients, as well as a reduction in neurofilaments, biomarkers that measure the level of neurodegeneration.
The challenge now is to translate this process to other molecular mechanisms. In addition to the SOD1 gene, other clinical trials are underway to treat other genetic forms of ALS, such as those caused by alterations in C9orf72, the most common, or FUS. These strategies represent a shift toward precision medicine in a disease that until now has had no curative treatment.
The right to genetic testing
The International Alliance of ALS Associations considers that all patients should have the right to access “genetic testing, genetic counseling, and up-to-date information on clinical genetics in ALS,” as stated in its declaration of fundamental rights for people with ALS. Increasingly, international guidelines are moving in the same direction.
Given the existence of a targeted therapy funded in our country, as well as various ongoing clinical trials, experts recommend that genetic testing be performed in all ALS patients, regardless of whether they have a family history.
Dr. Ángela Genge, Director of the Global Centre for ALS Excellence at the Montreal Neurological Institute, believes it is important to have genetic information from all patients with this condition, to ensure access to clinical trials and to be prepared in case a new targeted treatment for a specific genetic form becomes available.
Even in cases where there is no family history, relevant genetic findings may emerge that are useful for accessing trials or understanding what to expect in the course of the disease.
Genetic counseling for family members
One of the most common questions after diagnosis is whether the disease can be passed on to children. Genetic analysis can identify when there is a familial risk and when there is not, as well as guide the testing of other family members if necessary. A genetic counselor is responsible for determining the next steps if a genetic component is detected.
Despite the uncertainty that this disease causes, we are living in a hopeful moment in ALS research, where precision medicine is paving the way for new approaches to the disease.
