venglustat + imiglucerase

Venglustat + imiglucerase is an investigational combination therapy for Gaucher disease type 3, a chronic neuronopathic lysosomal storage disorder. **Venglustat** is an oral, brain-penetrant, selective inhibitor of glucosylceramide synthase (UDP-glucose ceramide glucosyltransferase), designed to reduce the synthesis of glucosylceramide and glucosylsphingosine, thereby addressing the substrate accumulation underlying Gaucher disease pathology. **Imiglucerase** is a recombinant enzyme replacement therapy that replaces deficient lysosomal acid β-glucosidase, facilitating substrate degradation in lysosomes. This combination is studied to target both systemic manifestations (via imiglucerase) and neurological involvement (via venglustat) in adults with Gaucher disease type 3. Phase 2 trials (LEAP, LEAP2IT) have shown venglustat crosses the blood–brain barrier, reduces biomarkers (glucosylceramide and glucosylsphingosine) in cerebrospinal fluid and plasma, and may provide neurological stability and increased functional brain connectivity in combination with ongoing imiglucerase therapy. Most adverse events are mild or moderate. No current approved therapies exist for the neurological manifestations of Gaucher disease type 3[1][2][4].

Other names

venglustat plus imiglucerase