A new study published in Brain and Development suggests that viltolarsen, a gene therapy targeting Duchenne muscular dystrophy (DMD), can slow disease progression and help maintain motor function in affected males. The study compared outcomes of patients receiving weekly viltolarsen infusions with those of age-matched controls over a three-year period.
Viltolarsen is designed to address mutations in the dystrophin gene by skipping exon 53, enabling the production of a functional dystrophin protein, which is crucial for muscle health. Its absence leads to the severe muscle wasting characteristic of DMD.
Study Details and Findings
The study involved 14 male patients aged 6 to 19 years with DMD, with 5 receiving weekly viltolarsen infusions. Among these, 4 maintained a consistent treatment schedule (at least 99.5% adherence) throughout the three-year study. Researchers reported that 3 of these 4 patients maintained motor function, while the fourth experienced only mild declines. In contrast, 8 of the 9 control group patients showed significant motor function deterioration over the same period.
According to the authors, "Currently, reports about intermittent viltolarsen treatment are limited. Therefore, further research on the molecular mechanism and the accumulation of similar cases is required to determine the efficacy and safety of intermittent viltolarsen treatment."
Patients receiving viltolarsen also maintained key physical abilities, such as sitting unassisted and climbing stairs without arm support, abilities that were lost in many untreated patients. These patients also demonstrated lower levels of serum creatine kinase, a marker of muscle damage, and larger left ventricular diastolic diameter.
Adverse Effects
The study reported several treatment-emergent adverse effects (TEAEs) in patients receiving viltolarsen, including proteinuria in all 5 patients, allergic rhinitis in 4, and eczema in 3. Other reported effects included upper respiratory infections, constipation, and headaches, though these were generally mild and resolved with or without treatment. Significant treatment-related adverse effects included localized swelling due to extravasation and lymph node enlargement from frequent infusions, both of which resolved without long-term complications. No major adverse events led to treatment discontinuation. However, 1 patient receiving intermittent viltolarsen experienced noticeable motor-function decline, underscoring the importance of uninterrupted weekly treatment.
Limitations and Future Directions
The study had several limitations, including the small sample size from a single institution and the retrospective nature of the analysis. The limited number of ambulatory patients precluded evaluations using specific motor function tests. The authors emphasize the need for further investigation with larger cohorts and longer follow-up periods to fully characterize the long-term efficacy and safety of viltolarsen.
"We believe that once-weekly and uninterrupted viltolarsen treatment will yield the expected results," the authors stated. "These findings warrant further investigation in the future using a larger number of cases and a longer follow-up period."
