How new gene therapies are transforming genetic testing for ALS
In Canada, approval of targeted treatment has driven broad surge
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- The approval of a gene-targeted therapy for ALS has revolutionized genetic testing in Canada, a study found.
- All ALS patients, including those with no family history, are now routinely offered genetic testing.
- This shift helps identify patients who may be eligible for specific treatments, such as the approved therapy Qalsody.
The anticipated availability and subsequent approval in Canada of the first gene-targeted therapy for certain people with amyotrophic lateral sclerosis (ALS) has transformed how doctors in the North American nation approach genetic testing for the rare neurodegenerative disease, according to a new study.
Over the last five years, Canadian ALS clinics have shifted from offering genetic testing mainly to people with a family history of ALS to routinely testing all patients, regardless of whether the disease appears to run in their family, the researchers found. Indeed, the data show 100% of physicians treating people with sporadic ALS — meaning their disease occurred spontaneously — now offer such testing.
The researchers say the change was influenced by the availability of Qalsody (tofersen), a medication conditionally approved in Canada in 2025, and the growing importance of identifying people eligible for treatment.
“Genetic testing practices in Canada shifted substantially during late-stage clinical development and following regulatory approval of a gene-targeted therapy,” namely Qalsody, the researchers wrote, adding that the new study findings illustrate how “therapeutic breakthroughs can redefine national clinical standards.”
The study, “A changed landscape: five-year retrospective on the paradigm shift in genetic testing practices for ALS in Canada,” was published in the European Journal of Human Genetics.
For many years, genetic testing in ALS was generally reserved for people with familial ALS, who have a known family history of the disease. People with sporadic ALS, who make up about 90% of cases and have no known affected relatives, were tested much less often because of the assumption this form of the disease lacked a genetic cause.
Guidelines now urge ALS genetic testing regardless of family history
However, research in recent years has shown that about 10% to 20% of sporadic ALS cases also have an identifiable genetic cause.
Reflecting this evidence, recent guidelines recommend offering genetic testing to everyone diagnosed with ALS, regardless of family history. The emergence of therapies targeting specific ALS mutations, as well as the need to determine eligibility for treatment, has further emphasized the importance of universal genetic testing, supporters say.
One example is Qalsody, conditionally approved in the U.S. in 2023 and in Canada two years later for people with ALS associated with mutations in the SOD1 gene. The RNA-based therapy is designed to lower levels of SOD1, the toxic protein that drives the disease in these patients.
Qalsody’s conditional approval was based on preliminary evidence from clinical trials showing that treatment reduced levels of neurofilament light chain (NfL), a marker of nerve damage, which regulators considered a good surrogate marker to predict its ability to slow disease progression. Confirmatory data will be needed for the treatment to advance to full approval.
Increase in testing in Canada linked directly to Qalsody approval
To evaluate how genetic testing practices have shifted in response to therapeutic developments, a team of researchers surveyed members of the Canadian ALS Research Network at three time points: in 2020, 2022, and 2025. CALS is a nationwide network currently consisting of 55 neurologists and physiatrists working across 24 specialized ALS clinics in Canada.
During the first two surveys, each clinic submitted a single response, while in 2025, multiple physicians from the same clinic were encouraged to participate to identify diverging practices within clinics.
In this final survey, researchers received responses from 33 physicians representing 21 of Canada’s 24 specialized ALS clinics. A total of 11 clinics took part in all three surveys, allowing the team to compare changes in practice over five years.
The surveys showed a dramatic increase in genetic testing for sporadic ALS. In 2020, one-third of physicians routinely offered genetic testing to these patients. That number rose to more than half (57%) in 2022 and reached 100% in 2025, meaning every responding physician reported routinely offering genetic testing regardless of family history.
Genetic testing for familial ALS was already common in 2020, with 93% of physicians routinely offering it, and reached 100% by 2025, the data showed.
Most physicians (78%) said their genetic testing practices had changed between 2020 and 2022, mainly due to broader access to comprehensive genetic testing and increased testing of people with sporadic ALS. By 2025, 61% reported that Qalsody’s approval had directly influenced how they approach genetic testing.
This study demonstrates a transformative paradigm shift in practice, marked by a surge in genetic testing for individuals with [no family history of ALS].
Changes extended beyond people with ALS. The proportion of physicians offering predictive genetic testing to healthy at-risk relatives increased from 37% in 2020 to 61% in 2025. The share who routinely monitored healthy people known to carry ALS-causing genetic mutations before symptoms also rose, from 30% to 44%, the data showed.
However, monitoring practices varied considerably among clinics, and several physicians said they routinely followed only people carrying SOD1 mutations because of the availability of Qalsody.
“This study demonstrates a transformative paradigm shift in practice, marked by a surge in genetic testing for individuals with [sporadic ALS],” the researchers concluded. “It highlights that, with the availability of a genetically targeted treatment and clear clinical utility, rapid adaptation in clinical practice is possible.”
Ellen Maugeri
this is so encouraging for people who have ALS mine is Sporadic but mine is PLS will there be any in the future to help all of us with different types of MND iam bounded by a wheelchair my speech is slurred i was diagnosed 2013 i suppose i should be more than i don’t have ALS but is it Sporadic the same as mine i would love to walk again and talk properly again i guess thats is along of way of or never as it’s the slowest one of MND can you comment on this for me any chance or a cure of PLS Sporadic