Researchers at the ALS Center Netherlands at University Medical Center Utrecht have identified new genetic abnormalities that play a role in the development of ALS. As a result, the proportion of patients for whom a genetic cause can be identified of the neuromuscular disease has increased from 20 to 25 percent. The discovery also improves understanding of the disease and may, in time, support the development of targeted treatments for a subset of patients.
The findings have been published in the scientific journal Nature Genetics and are part of the international research initiative Project MinE. “This discovery does not mean there will be a drug tomorrow, but it does give clear direction for follow-up research,” says Jan Veldink, professor of neurology and neurogenetics and principal investigator of Project MinE.
For the study, researchers analyzed the DNA of nearly 18,000 people with ALS and more than 200,000 individuals without the disease. They identified several genetic variants associated with an increased risk of ALS, including variants in the ARPP21 gene. These findings provide new leads for the development of treatments.
Through GoALS, a large-scale ALS research program of which Project MinE is a part, scientists are working on new therapies. It is expected to take several more years before these may become available. Veldink: “We are now moving forward to develop potential gene therapies together with partners.”
Familial and sporadic ALS explained
Each year, around 500 people in the Netherlands are diagnosed with ALS. There are two forms of the disease: familial and sporadic. Familial ALS means that multiple family members are affected, suggesting a strong genetic cause. In sporadic ALS, genetic factors may still play a role, but environmental factors are also likely involved. About one in ten people with ALS has the familial form, while 90 percent have sporadic ALS. Overall, at least 25 percent of all people with ALS, regardless of family history, carry a genetic abnormality.
For most people with ALS, no effective treatment is yet available. In 2022, the drug QALSODY (also known as Tofersen) marked the first breakthrough for a genetic form of ALS. This therapy targets patients with a rare mutation in the SOD1 gene, representing about one percent of ALS patients in the Netherlands.
Nature Genetics
Observational study
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