15 June 2026
News
Amyotrophic lateral sclerosis (ALS) remains one of the most serious and difficult-to-treat neurodegenerative diseases. At the initiative of the FilSLAN rare disease health network, and with the support of the ACT4ALS-MND national clinical research network (F-CRIN-certified), which it leads and coordinates, a multicenter data collection effort has been established on a national scale. It yields promising results regarding Tofersen, the first treatment to directly target a genetic abnormality responsible for certain forms of the disease. Conducted among patients carrying a SOD1 gene mutation who were followed at 19 French expert centers, this study suggests a significant slowing of disease progression and reinforces the data obtained from the 146-week follow-up of patients included in the VALOR trial.
A rare genetic form that is central to ALS research
Amyotrophic lateral sclerosis (ALS), also known as Charcot's disease, is a neurodegenerative disease that progressively destroys motor neurons, the nerve cells responsible for controlling voluntary movements. This condition leads to progressive paralysis, a growing loss of independence, and, in most cases, respiratory failure.
While the majority of cases occur sporadically, approximately 10% of patients have a genetic form of the disease. Among these, SOD1 gene mutations hold a special place in the history of ALS research. Identified as early as the 1990s, they were the first genetic abnormalities identified in familial forms of the disease and today account for approximately 1 to 2% of all cases.
The progression of these genetic forms is highly variable: some patients experience a relatively slow progression while others develop a much more aggressive disease. This diversity underscores the importance of personalized therapeutic approaches tailored to patients’ genetic profiles.
Tofersen: A Targeted Therapeutic Approach
Tofersen represents a major breakthrough in the treatment of patients with ALS caused by a mutation in the SOD1 gene. Administered intrathecally, this treatment aims to reduce the production of the abnormal SOD1 protein, which is responsible for the degeneration of motor neurons.
The first international clinical trials have shown a significant decrease in plasma neurofilaments, now considered reliable biomarkers of neurodegenerative activity in ALS. Longer-term follow-ups have also suggested that early intervention could help slow the progression of the disease.
A particularly encouraging real-world study from France
To assess the impact of treatment under real-world conditions, a French multicenter study was conducted in 46 patients with SOD1-mutation-related ALS treated with Tofersen at 19 expert centers.
The results show a significant slowing of clinical progression following the initiation of treatment. The rate of functional decline, measured by the ALSFRS-R scale, appears significantly slower during follow-up, decreasing on average from approximately 0.53 points per month before treatment to 0.22 points per month after 12 months.
At the same time, neurofilament levels decreased sharply, with a reduction of approximately 67% after one year of treatment, reflecting a decline in neurodegenerative activity.
Beyond slowing disease progression, researchers also observed encouraging results regarding survival. These data reinforce the signals already observed in international studies and provide new evidence supporting the value of the treatment in the management of genetic forms.
Real-world data: an essential tool in rare diseases
For rare diseases such as hereditary ALS, conducting large-scale clinical trials remains particularly challenging due to the small number of affected patients. Data from daily clinical practice therefore serve as a valuable complement to clinical trials and allow for a better assessment of the real-world impact of therapeutic innovations.
The work conducted by the expert centers of the FilSLAN network, brought together by the ACT4ALS-MND (F-CRIN) network, has notably provided new evidence supporting the clinical efficacy of Tofersen in real-world conditions. These data have also helped expand the available knowledge on this treatment and document its benefits for patients with SOD1-related ALS.
A new step toward precision medicine
These results mark a very important step in the management of ALS. They illustrate the progress made in understanding the genetic forms of the disease and highlight the importance of early genetic diagnosis as well as the development of reliable biomarkers.
“In a disease that has long lacked treatments capable of altering its course, the results observed with Tofersen represent one of the most encouraging signs in recent years. For the first time, we are demonstrating that it is gradually becoming possible to directly target certain genetic causes of ALS ,” notes Professor Philippe Couratier, coordinator of the ACT4ALS-MND (F-CRIN) network, head of the Limoges ALS Center, and leader of the FilSLAN rare disease network.
The FilSLAN rare disease healthcare network is dedicated to organizing, coordinating, and strengthening care for patients with ALS and motor neuron diseases on a national scale. It brings together reference, resource, and center-of-expertise centers, as well as stakeholders in healthcare, research, and medical-social services, along with patient associations, to improve the healthcare journey and quality of life for those affected. Created as part of the National Rare Diseases Plan, FilSLAN works to develop collaborative projects aimed at harmonizing practices, promoting access to diagnosis and therapeutic innovations, and supporting clinical and translational research. It also plays a key role in disseminating knowledge, training healthcare professionals, and providing information to patients and their families. Through this collective effort, FilSLAN helps raise awareness of these conditions, accelerate scientific progress, and promote comprehensive, coordinated, and equitable care across the country. https://portail-sla.fr
The national clinical research network for ALS, the Alliance on Clinical Trials for Amyotrophic Lateral Sclerosis – Motor Neuron Disease (ACT4ALS-MND) is primarily dedicated to pooling the expertise of ALS centers and leveraging the very large cohort of patients under observation to develop therapeutic trials and national or collaborative European and international clinical studies. Operational since the summer of 2020, several projects are already underway (new drugs, gene therapy protocols). Co-coordinated by Prof. Philippe COURATIER, head of the ALS/MND Center at Limoges University Hospital, Prof. Gaëlle BRUNETEAU, the Paris ALS Center, Prof. Julien CASSEREAU of the Angers ALS Center, Prof. David DEVOS of the Lille University Hospital, and Dr. Aude-Marie GRAPPERON of Marseille ALS Center, ACT4ALS-MND aims to facilitate and energize clinical research in France, whether academic or industrial, in the field of ALS and motor neuron diseases. For more information: https://act4als.org
Established in 2012, F-CRIN (French Clinical Research Infrastructure Network) is a national platform dedicated to advancing clinical research in France. It is led by Inserm in partnership with hospitals, healthcare companies, and universities, and supported by the French National Research Agency and the Ministry of Health. Its mission is to bring together clinical research stakeholders to strengthen the competitiveness and international appeal of French research, develop professional expertise by pooling know-how, resources, and capabilities, and thereby accelerate the adoption of new practices and the development of new therapeutic solutions. Today, F-CRIN is based on a federative model structured around 28 components: 26 thematic networks for research and clinical investigation, a state-of-the-art multi-service platform available to sponsors and investigators to support their trials, and a national coordination unit, the infrastructure’s headquarters, located in Toulouse. With more than 2,000 professionals pooling their expertise and resources, F-CRIN also serves as the French interface for the European clinical research network ECRIN, promoting the participation of French teams and centers in multinational clinical trials. For more information: https://www.fcrin.org
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