Orphan drug status to PBGM01 for treating GM1 gangliosidosis

May 9, 2020 0 By FM

The US FDA has granted Orphan Drug Designation to its lead product candidate, PBGM01, for the treatment of infantile GM1 gangliosidosis (GM1).

GM1 is a rare and often life-threatening monogenic recessive lysosomal storage disease caused by mutations in the GLB1 gene that results in rapidly progressing neurodegeneration.

PBGM01 is an AAV-delivery gene therapy currently being developed for the treatment of infantile GM1, in which patients have mutations in the GLB1 gene causing little or no residual ß-gal enzyme activity and subsequent neurodegeneration. 

PBGM01 utilizes a next-generation AAVhu68 capsid administered
through intra-cisterna magna (ICM) to deliver a functional GLB1 gene encoding ß-gal to the brain and peripheral tissues. By reducing the accumulation of GM1 gangliosides, PBGM01 has the potential to reverse neuronal toxicity, thereby restoring developmental potential. 

In preclinical models, PBGM01 has demonstrated broad brain distribution and wide uptake of the ß-gal enzyme in both the CNS and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1.