Summary: Researchers at Umeå University report a major advance in treating amyotrophic lateral sclerosis (ALS) using a targeted gene therapy. In a patient with an aggressive SOD1-related form of ALS, the therapy has markedly slowed disease progression. Four years after starting treatment in early 2020, the patient retains much of their mobility, speech and daily independence—outcomes well beyond typical expectations for this form of the disease.
The therapy specifically targets mutations in the SOD1 gene, lowering levels of the misfolded SOD1 protein and stabilizing clinical decline. These clinical observations, together with biomarker improvements, offer cautious optimism for gene-targeted approaches in ALS and potential future combination treatments tailored to different ALS subtypes.
Key Facts:
- Targeted gene therapy: The experimental treatment lowers levels of the disease-associated SOD1 protein, which is implicated in motor neuron degeneration in SOD1-related ALS.
- Notable patient outcome: Four years after diagnosis and regular treatment, the patient continues to perform daily activities independently—an unusual outcome for aggressive SOD1-linked ALS.
- Regulatory progress: The drug has been approved by the U.S. Food and Drug Administration (FDA) and recommended by the European Medicines Agency (EMA) for patients with SOD1 mutations, reflecting supportive regulatory assessments.
Source: Umeå University
Breakthrough in ALS gene therapy research
Scientists at Umeå University and the University Hospital of Northern Sweden report that a new gene therapy has substantially slowed clinical progression in a patient with a particularly aggressive SOD1 mutation causing ALS. After beginning treatment in 2020, the patient maintains active participation in family and social life and retains key motor functions such as climbing stairs, standing from a chair, speaking clearly and eating without assistance.
“I consider this a breakthrough for the research we have conducted for more than 30 years at Umeå University and the University Hospital of Northern Sweden,” says Peter Andersen, neurologist and professor in the Department of Clinical Sciences. “We have never before seen treatment results as effective as these with any other therapy.”
The patient comes from a family in southern Sweden affected by an aggressive SOD1 mutation. After a relative received an ALS diagnosis, the patient provided a blood sample to the research team but initially chose not to learn the genetic result. When muscle weakness developed four years ago, the patient was diagnosed with early-stage ALS and immediately entered medical care.
Starting in the summer of 2020, the patient enrolled in a Phase III clinical trial of the gene therapy designed for SOD1 mutations that cause misfolding and aggregation of SOD1 protein in motor neurons. The treatment was administered every four weeks at a university hospital in Copenhagen, Denmark.
Biomarker reduction of nearly 90%
At diagnosis in 2020, the patient’s neurofilament light chain (NfL) level—a sensitive biomarker of neuronal injury—was extremely elevated. Over the subsequent four years and following 50 doses of the experimental drug, measured NfL levels fell by almost 90%.
“When the patient was diagnosed in April 2020, neurofilament L measured around 11,000 ng/L, which is high even for ALS patients,” Peter Andersen explains. “In the most recent samples, levels are down to approximately 1,200–1,290 ng/L, a substantial reduction of this disease indicator.”
Blood measurements have shown a continued fall of neurofilament toward the normal range for the patient’s age. More broadly, the patient’s clinical function—measured by the ALS Functional Rating Scale Revised (ALSFRS‑R)—has remained stable at approximately 35–37 points over the last 18 months, indicating a roughly 26% reduction compared with a healthy individual while avoiding the rapid monthly decline expected for this mutation type.
Without treatment, patients with similarly aggressive SOD1 mutations typically lose 1–1.5 ALSFRS‑R points per month and face rapid disability and shortened survival. “That this patient can, more or less unimpeded, still climb stairs four years after disease onset is remarkable,” says Karin Forsberg, neurologist and long‑time SOD1 researcher at the Department of Clinical Sciences.
Forsberg emphasizes that the drug is not a cure but appears to slow progression: “It gives us significant hope and a path forward for developing pharmaceutical strategies for ALS patients.” Only 2–6% of ALS cases are caused by SOD1 mutations; some are familial and others occur sporadically. Whether this therapy will benefit other ALS types remains unknown and requires further research.
The patient continues to perform most activities independently—speech remains intact, and daily tasks such as mowing the lawn, shopping and caring for children are still managed without assistance. The emotional impact is also profound: the patient reports improved mental well‑being and renewed hope.
‘This is only the beginning’
The clinical study in which the patient is enrolled concludes this summer. While the medication is not yet available in Sweden, it has received FDA approval in the United States, and on 23 February 2024 the European Medicines Agency recommended its use for patients with SOD1 mutations in the European Union. Swedish health authorities have requested health-economic evaluation before routine regional prescribing is implemented.
“Our next step is to analyze outcomes across treated patients,” Forsberg says. “Some patients respond strongly while others show less benefit. Differences may relate to dose, timing of treatment onset, or the need for complementary therapies. Perhaps a combination of drugs will eventually be required to halt disease progression fully. This is only the beginning.”
The research team is seeking ethical approvals to study potential compensatory mechanisms activated by the therapy. “Understanding these mechanisms may reveal previously unknown aspects of nervous system function and point to improved or additional drug targets,” Peter Andersen notes.
About this ALS and gene therapy research news
Author: Peter Andersen
Source: Umeå University
Contact: Peter Andersen – Umeå University
Image credit: Neuroscience News
Original Research: The findings will appear in eLife.