Opportunity for ALS patients

ALS (from amyotrophic lateral sclerosis) is a rare, debilitating and rapidly progressive disease that belongs to the group of neurodegenerative diseases. In the brain and spinal cord, affected individuals experience damage and loss of motor neurons, known as motoneurons. As the disease progresses, patients gradually lose the ability to move, speak, swallow and eventually breathe on their own. The average life expectancy in ALS is 3 to 5 years from the first symptoms of the disease. The main cause of death is respiratory failure. In May 2024, there was a breakthrough in the treatment of this severe disease in a mutation in the SOD1 gene . The Department of Neurology at PIM MSWiA, as one of the few centers in Poland, has the opportunity to conduct an early access to therapy (EAP) program, already closed to new patients, evaluating the effectiveness and effects of treatment on a group of Polish patients with SOD1-ALS.

The Department of Neurology of the Ministry of Internal Affairs and Administration, as one of the few centers in Poland, runs an early access program for tofersen therapy in patients with mutations in the gene SOD1 [at. ed. recruitment to the EAP program is now closed]. When was this program started and what are the preliminary results of clinical observations of treatment efficacy and effects?

We put our first patient on the treatment in October 2023. At the moment we have 7 patients in the group who have been on treatment for 19 months, and they are after already 22-23 administrations of the drug, so the follow-up is relatively long compared to other groups in the world. The effects are very satisfactory for both us and the patients. We are seeing improvements in the patients' day-to-day functioning. This is reflected in the evaluation scale. We are seeing positive effects in the cerebrospinal fluid study. These effects are as expected, so in summary, both we and the patients are satisfied.

How is this progress monitored?

Patients are assessed each time on the ALS-FRS scale, which evaluates functioning in specific functional systems. In this disease, all kinds of motor, movement functions are gradually damaged. And this is subject to assessment. This scale is used to assess both the progression of the disease and to monitor treatment. And while before the inclusion of treatment, these patients showed a gradual decrease in scores on this scale, which indicates disease progression, since the inclusion of treatment in these patients, scores on this scale have either increased or stabilized - they stand still, so this is a very positive effect. The drug is administered intrathecally, through lumbar punctures, which provides an opportunity to collect cerebrospinal fluid each time it is examined. The fluid undergoes a general examination and testing of neurofilament levels, which is the purpose of tofersen. Its purpose is to reduce the level of a toxic protein that is the product of a mutated gene.

Tofersen is supposed to lower the level of this protein, and we see that the level of neurofilaments, which this correlates with the level of this protein, is dropping, so the drug is working.

What are the benefits of treatment for patients?

Patients benefit mainly in daily functioning. They are able to remain independent longer, independent of others, active at work, and are not a burden on either loved ones or society.

And a final question. How does access to therapy change the natural course of the disease?

Without treatment, as I mentioned before, progression is faster for some and slower for others. But it is often very fast, and within a few years the patient unfortunately becomes bed-ridden and passes away. In contrast, in patients treated with tofersen, we see stabilization and sometimes even a slight improvement.