Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis

Area of Science:

• Biochemistry
• Genetics
• Pharmacology

Background:

• Gaucher's disease is characterized by glucocerebroside accumulation in lysosomes.
• Current intravenous enzyme replacement therapy is invasive.
• Developing oral treatments that reduce substrate biosynthesis is a key therapeutic goal.

Purpose of the Study:

• To investigate the safety and efficacy of OGT 918 (N-butyldeoxynojirimycin) as an oral treatment for non-neuronopathic Gaucher's disease.
• To assess the impact of OGT 918 on organ volumes and biochemical markers.

Main Methods:

• A 1-year open-label study involving 28 adults with non-neuronopathic Gaucher's disease.
• Patients received 100 mg of oral OGT 918 three times daily.
• Liver and spleen volumes were measured by imaging; biochemical and hematological variables, including chitotriosidase activity, were monitored monthly.

Main Results:

• Significant reductions in mean liver volume (12%) and spleen volume (19%) after 12 months of treatment (p<0.001).
• Mean chitotriosidase concentrations decreased by 16.4% (p<.0001).
• Most frequent adverse effect was diarrhea (79%); six patients withdrew due to various reasons.

Conclusions:

• OGT 918 effectively decreases substrate formation, leading to improved clinical features in non-neuronopathic Gaucher's disease.
• This oral substrate reduction strategy warrants further investigation for Gaucher's disease and other glycosphingolipid storage disorders.