In recent years, access to modern therapies has changed the quality of life of patients with spinal muscular atrophy (SMA). Treatment has not only stopped disease progression, but has also enabled patients to regain lost motor functions. New clinical studies indicate that higher doses of an intrathecal drug, already approved in Europe and the United States, may activate previously “dormant” motor neurons responsible for muscle movement. This could translate into further functional improvement for patients with SMA.
“We have very interesting clinical trial results showing, among other things, that patients switched to a high dose of nusinersen achieve an additional positive functional effect. It appears to be closely related to the possibility of awakening some inactive motor cells, motor neurons that are still capable of regaining function, or of restoring function to the entire motor unit,” said Prof. Anna Kostera-Pruszczyk, head of the Department and Clinic of Neurology at the Medical University of Warsaw and the Central Clinical Hospital of the University Clinical Centre of the Medical University of Warsaw, in an interview with Newseria.
Motor neurons transmit signals to muscles and enable basic activities, from movement to breathing and swallowing. In the course of SMA, some of them die irreversibly. However, research shows that there is also a group of cells that remain inactive while retaining the potential to function. This “reserve” may be crucial for further improvement in patients.
“A high dose is able to reach a certain pool of motor neurons that were not active; we provisionally call them dormant. The effect is relatively fast. It does not appear to be directly related to reinnervation, meaning available motor neurons doing heavier work, but rather to an additional pool of motor neurons joining the collective effort,” Prof. Kostera-Pruszczyk said.
Nusinersen treatment has been used globally since 2016, and in Poland it has been widely available since 2019. Administered intrathecally, the therapy acts directly within the nervous system. Initially, its introduction was expected primarily to halt disease progression, but clinical practice has shown much greater potential.
“When we said that we were beginning the era of treatment for spinal muscular atrophy, we expected that we could stop the disease process and halt the progression of disability in patients. It turned out, however, that the vast majority, around 80% of patients, achieve not only this stabilisation but also improvement, which we are able to measure using appropriate functional scales,” said Prof. Katarzyna Kotulska-Jóźwiak, chair of the Council for Rare Diseases and head of the Department of Neurology and Epileptology at the Children’s Memorial Health Institute.
The functional scales used in SMA make it possible to assess even small changes in patients’ abilities with precision. In a progressive disease, even an improvement of a few points can mean a real difference in everyday functioning, from greater independence to the ability to perform simple tasks without assistance. Data from the B102 drug programme show that in children with the most severe form of SMA, improvement on the CHOP-INTEND scale averaged 5 points after just three months of therapy and reached 15 points after more than a year. In patients with milder forms of the disease, improvement exceeded 8 points, while an increase of at least 4 points is already considered clinically significant.
Further analyses indicate that increasing the dose may affect not only patient functioning, but also markers of nerve cell damage.
“A higher dose is associated with a faster effect on the biomarker of neuronal damage, namely neurofilament levels. It is also associated with a reduced risk of infections or respiratory complications that require hospitalisation,” Prof. Kotulska-Jóźwiak said.
Neurofilaments are markers of nerve cell damage that help assess disease activity and treatment effectiveness. A faster decline in their levels observed with higher doses may indicate stronger neuronal protection and reduced neurodegeneration. This suggests that higher dosing may not only improve patients’ functioning, but also better protect nerve cells from further degradation.
“Studies have shown that patients treated for an average of about four years with a 12 mg dose improved significantly within 10 months of receiving a higher dose, followed by higher maintenance doses over the next two years, both on the Hammersmith scale and the RULM scale. After four years, more than 60% of patients recorded what is known as a clinically meaningful improvement. We can see that there is potential in the higher dose,” said Dr Anna Łusakowska from the Department and Clinic of Neurology at the Medical University of Warsaw and the Central Clinical Hospital of the University Clinical Centre of the Medical University of Warsaw.
These results come from clinical trials comparing the standard treatment regimen of 12 mg with higher doses of the drug: a 50 mg loading dose and a 28 mg maintenance dose. The studies also included patients who had previously remained on standard-dose therapy for several years and had achieved at least disease stabilisation. Observations suggest that additional improvement may appear in a relatively short time after changing the dosing regimen, which may confirm the potential of treatment intensification also in later stages of the disease.
The higher-dose regimen may also be considered in patients treated with other available therapies who have not achieved a sufficient response.
“If we feel that a patient is not benefiting enough from a given treatment, a change may need to be considered. It certainly needs to be considered when biomarkers such as neurofilaments show an increase, indicating disease activity,” Dr Łusakowska said. “Collecting data from real-world clinical practice will show us which patients benefit the most, so we may be able to personalise this therapy more effectively.”
In January 2026, the European Commission, following an earlier positive recommendation from the European Medicines Agency, granted marketing authorisation for higher doses of the drug. In Poland, an administrative process is currently underway at the Ministry of Health to expand the drug programme.
“We know how intrathecal treatment works and that it is very effective, which is why we believe that a higher dose will bring even greater progress, more possibilities and better outcomes,” said Dorota Raczek, president of the SMA Foundation. “We hope that the higher dose will soon also be available in Poland.”
She emphasised that response to treatment often means improved patient functioning, which directly translates into greater independence. This applies both to basic everyday activities and to social or professional activity, which in many cases had previously been beyond patients’ reach.
“Lifting a full glass of water may seem like nothing to us, but for patients with SMA it is a lot. Patients can work longer, speak for longer or even give up non-invasive ventilation. Treatment makes their quality of life much better,” Dorota Raczek said.
