A targeted drug has passed a Phase III trial in a rare genetic form of the disease, and a ten-protein blood panel has separated patients from healthy people with high accuracy. Neither is a cure, but two years after the death of Dániel Karsai, the outlook for amyotrophic lateral sclerosis looks different.
Dániel Karsai was a Hungarian constitutional lawyer who became widely known when he turned to the European Court of Human Rights in Strasbourg, seeking the right to end his life with dignity while living with ALS. Hungarian law bans euthanasia and also criminalises helping someone travel abroad to die. The Court rejected his claim in June 2024, and he died shortly afterwards at the age of 47.
His case returned to the Hungarian conversation when former minister János Kóka wrote in a Facebook post on 5 November that two recent scientific results may give ALS patients new hope. He asked whether, a few years from now, people in Karsai’s position could be treated. The two results are real and interesting, and the post is careful to say that the goal is still far off.
A drug aimed at the cause
On 22 September, Ionis Pharmaceuticals and Otsuka announced that ulefnersen met the primary endpoint of the Phase 3 FUSION trial in people with FUS-ALS. The endpoint is a joint-rank measure that combines functional decline and survival, and according to the companies’ announcement the difference from placebo was statistically significant. Secondary measures, including a blood marker of nerve damage and time to death or permanent ventilation, also pointed the same way.
Ulefnersen is an antisense therapy. It reduces the production of the FUS protein, which accumulates in motor neurons in this form of the disease, and it is given by lumbar puncture so that it reaches the central nervous system directly. It is the second antisense drug, after tofersen for SOD1-ALS, to show it can change the course of a genetic form of ALS.
The patient group is small. FUS-ALS accounts for an estimated 0.6 per cent of all ALS cases, but it is the most common genetic cause of juvenile ALS and often progresses quickly in young people. The data so far are topline results from a company announcement. Detailed results are to be presented at a congress and submitted to a peer-reviewed journal in the coming months, and it is not yet known when the drug might be approved or available. It has orphan designation from the European Medicines Agency, among other regulators.
A blood test that is not yet a test
The second result is diagnostic. In a study in Nature Communications, researchers at Emory University measured hundreds of proteins in blood plasma and arrived at a panel of ten, analysed with machine learning. In an independent validation cohort, the panel distinguished ALS patients from healthy controls with 98.3 per cent balanced accuracy, compared with 89.9 per cent for neurofilament light chain alone. Kóka summarises the result as 143 of 144 patients identified correctly. The published summary reports the balanced figure, which averages how well a test recognises the sick and the healthy.
The authors themselves call it a research finding, not a validated diagnostic test. Patients were compared only with healthy people, while a clinical test would also have to separate ALS from other neurological diseases with similar symptoms. The practical promise is speed: a reliable blood test could shorten the path to specialist care, which matters in a disease where the diagnosis often comes late.
Putting the two together
Kóka’s central picture is a simple blood draw that flags the disease early, followed by a treatment that halts the loss of nerve cells. As a direction of travel, it is reasonable. The panel indicates whether someone is likely to have ALS, not which genetic subtype, so finding candidates for a drug like ulefnersen would still require genetic testing. Most patients also have forms of ALS for which no targeted therapy exists, and Kóka says as much.
His historical comparisons point the same way. In 1991, when Freddie Mercury died, an HIV diagnosis was close to a death sentence, and treated patients today can expect a near-normal lifespan. Childhood leukaemia was once almost always fatal, and most children now recover. In both cases, decades of incremental work separated the first promising results from routine care.
What it means for Central and Eastern Europe
For the region, the near-term question is about access more than science. A therapy for a subtype that accounts for under one per cent of cases will concern very few patients in any one country. As a rough illustration, ALS incidence in Europe is on the order of two to three new cases per 100,000 people a year, which in a country the size of Hungary suggests one or two new FUS-ALS patients annually. That is an estimate, not registry data. Reaching those patients would depend on genetic testing being offered to people with ALS, especially younger ones. It would also depend on how quickly regulators and health insurers in the region deal with a high-cost orphan drug once it is approved in Europe.
Karsai’s case showed that Hungary’s debate about the end of life is partly a debate about what medicine can offer before that point. Neither new result would have changed his own diagnosis. They do suggest that the field is moving from describing ALS to intervening in it, one genetic subtype at a time.
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