GM1 Gangliosidosis—PBGM01

About PBGM01:

We are developing PBGM01 to treat infantile GM1 with a single dose of PBGM01 by intra-cisterna magna injection. PBGM01 utilizes a next-generation AAVhu68 viral vector to deliver modified DNA encoding the b-gal enzyme to a patient's cells. The goal of this vector and delivery approach is to increase levels of the b-gal enzyme in both the central nervous system (CNS) and the peripheral nervous system (PNS).

About GM1:

GM1 is a rare and often life-threatening monogenic recessive lysosomal storage disease that results in progressive damage to both the CNS and the peripheral tissues. The infantile form of the disease is characterized by onset in the first year of life with symptoms including hypotonia (reduced muscle tone), progressive CNS dysfunction leading to deafness, blindness, rigidity and progressive skeletal dysplasia that leads to restrictive lung disease and aspiration pneumonia. The disease rapidly progresses, with a life expectancy of two to four years.

GM1 is caused by recessive mutations in the GLB1 gene, which encodes lysosomal acid beta-galactosidase (β-gal) an enzyme that catalyzes the first step in the natural degradation of GM1 ganglioside. Reduced -gal activity results in the accumulation of toxic levels of GM1 ganglioside in neurons throughout the brain, causing rapidly progressing neurodegeneration. GM1 manifests as a continuum of clinical severity, ranging from infants with earlier onset and more severe and rapidly progressive disease to those with later juvenile or adult onset, slower progression and less severe manifestations.

The global incidence of GM1, is estimated to be 0.5 to 1 in 100,000 live births. Infantile GM1 represents approximately 62.5% of such cases. Currently, there are no approved disease-modifying therapies available. Supportive treatment options include the use of feeding tubes or ventilators for infants with GM1.