Miglustat may slow physical decline in juvenile Batten disease: Study
Treated patients had slower rate of impairment progression
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Miglustat, an investigational oral medication currently in early clinical testing for Batten disease, was tolerated well in a small study that evaluated the therapy in six people with juvenile Batten disease.
Trial data indicate that the miglustat-treated patients had a slower rate of progression in physical impairment than is typically seen in untreated patients with juvenile Batten disease. While researchers emphasized that further studies are necessary, they noted that these data provide support for miglustat as a potential therapy for juvenile Batten disease.
The study, “Long-Term Open-Label Study Evaluating Oral Miglustat Treatment in Patients With Neuronal Ceroid Lipofuscinosis Type 3,” was published in Neurology. The Italian Ministry of Health funded the work.
Miglustat inhibits production of fatty molecules
Juvenile Batten disease, also known as CLN3 disease, is caused by genetic mutations that lead to certain fatty molecules accumulating to toxic levels in cells.
Miglustat, developed by Theranexus, is a medication designed to inhibit the production of these fatty molecules, thus reducing the toxic buildup and ultimately slowing disease progression. The therapy, which is also known as Batten-1, has shown promise as a potential juvenile Batten therapy in a Phase 1/2 clinical trial (NCT05174039).
This study included six people with juvenile Batten, ages 10 to 25, all of whom were treated with miglustat. All of the patients had begun showing symptoms in childhood, which is consistent with the typical trajectory of juvenile Batten disease. In most patients, the dose of miglustat was gradually increased to 600 mg/day; one patient was maintained on a lower dose of 300 mg/day.
The observed slower deterioration in our cohort suggests that miglustat may influence the rate of physical impairment progression in patients with CLN3.
The study’s main goal was to evaluate how miglustat treatment affects trajectories on the physical subscale of the Unified Batten Disease Rating Scale, a standardized assessment of Batten disease severity. Over a median follow-up of nearly four years, scores on this subscale worsened at a rate of about two points per year on average. This result contrasts with historical data from untreated people with juvenile Batten, where scores have been reported to worsen at a rate closer to three points per year.
“The observed slower deterioration in our cohort suggests that miglustat may influence the rate of physical impairment progression in patients with CLN3,” the researchers wrote, though they cautioned that it’s impossible to draw definitive conclusions from this small study, which did not include a placebo group. “While the results suggest a slower rate of physical decline in treated patients compared with historical data, confirmation through larger, randomized, placebo-controlled trials [is] essential.”
Miglustat was generally well-tolerated in the study. Some patients reported mild gastrointestinal side effects, such as bloating or diarrhea, but these were generally mild and resolved over time.
“It is important to note that miglustat demonstrated a favorable safety and tolerability profile over the course of this study,” the researchers wrote, adding that the results overall “contribute to the growing body of evidence supporting the potential role of miglustat as a therapeutic option for CLN3 disease.”
Miglustat is approved under the name Zavesca as a treatment for Gaucher disease, and it is part of Pombiliti + Opfolda, an approved treatment for Pompe disease. Like Batten, Gaucher, and Pompe diseases are marked by the toxic buildup of fatty molecules in cells.
