Selenium levels found elevated in ALS patients treated with Qalsody
Therapy prevents toxic SOD1 from being produced
Both beneficial and neurotoxic forms of the mineral selenium were increased in people with SOD1-associated amyotrophic lateral sclerosis (ALS) after six months of treatment with Qalsody (tofersen), a report shows.
The elevations, which have been linked to ALS previously, could reflect a change in the antioxidant status of nerve cells, but more studies will be needed to determine the finding’s clinical relevance.
“Overall, these findings suggest that tofersen treatment markedly alters selenium status … within the central nervous system, possibly due to a direct effect on neurons,” the researchers wrote.
The study, “Changes in Cerebrospinal Fluid Concentrations of Selenium Species Induced by Tofersen Administration in Subjects with Amyotrophic Lateral Sclerosis Carrying SOD1 Gene Mutations,” was published in Biological Trace Element Research.
The cause of ALS isn’t fully established, but a leading genetic factor associated with the disease is the SOD1 gene. Normally, SOD1 produces an antioxidant enzyme — named SOD1 — that helps prevent oxidative stress, a type of cellular damage where toxic oxidant molecules overpower the antioxidants that combat them.
ALS-associated SOD1 mutations lead to an abnormal form of SOD1 being produced that accumulates to toxic levels and isn’t able to properly perform these duties, driving damage to motor neurons, that is, the nerve cells involved in muscle control.
Effects of Qalsody on selenium
Qalsody is an injectable therapy that prevents toxic SOD1 from being produced to help protect nerve cells and slow disease progression. It was conditionally approved in the U.S. last year for SOD1-ALS patients and was approved under exceptional circumstances in the European Union in May.
How the therapy affects redox status in the central nervous system, or brain and spinal cord, hasn’t been established. Redox status refers to the balance of oxidants and antioxidants that informs whether oxidative stress will occur.
Selenium and its related proteins are important in redox status. The mineral can have pro- or antioxidant effects, depending on its chemical form. Indeed, while studies have found selenium exposure to be a risk factor for ALS, selenium-based compounds have been studied as a possible treatment for SOD1-ALS.
Here, scientists studied whether concentrations of different forms of selenium were altered by Qalsody among 10 adults with SOD1-ALS who were receiving the medication under an expanded access program in Italy. The patients had a median age of 58.6 and had been living with ALS symptoms for a median of 50 months, or a little over four years, when they started Qalsody.
A baseline measure of selenium in the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, was taken before Qalsody was initiated and again after six months.
At baseline, selenium bound to selenoprotein P, the species in highest abundance, which remained the case after six months on Qalsody. Both beneficial and adverse effects of the selenoprotein P complex in the body have been described.
There was a notable increase in CSF concentrations of overall selenium, along with across nearly all specific types of the element, after treatment.
The greatest increases were seen for thioredoxin reductase-bound selenium, a form linked to antioxidant activity, and human serum albumin-bound selenium, which has a more controversial function. For these forms, levels after six months were three and nine times higher relative to baseline.
A few major selenium species known to be neurotoxic exhibited substantial increases with treatment.
In general, greater increases in selenium forms were correlated with slower rates of functional and lung function decline, but the findings varied.
Changes in selenium after Qalsody treatment could be part of a “compensatory, beneficial response” that sought to normalize nerve cells’ redox status and fight oxidative stress.
However, increases in neurotoxic selenium may be due to overall increased selenium absorption in the brain, or to disease progression, or the injection. There was no untreated control group, meaning more research is needed to establish a reason.
“Further studies are required to investigate the biological and clinical relevance of these findings and how they might relate to the pharmacological effects of the drug and to disease progression,” the researchers wrote.
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