PBML04

PBML04 is an investigational gene therapy designed for the treatment of metachromatic leukodystrophy (MLD), a rare, fatal pediatric lysosomal storage disorder. The therapy utilizes an adeno-associated virus (AAV) vector—specifically the proprietary AAVhu68 capsid—to deliver a codon-optimized gene encoding functional arylsulfatase A (ARSA) enzyme to the central nervous system. MLD is caused by mutations in the ARSA gene, leading to deficiency of this enzyme and subsequent accumulation of toxic sulfatides in neural tissues. Preclinical studies have shown that PBML04 can reduce neurological deficits in animal models by restoring ARSA activity. Originally developed through a collaboration between Passage Bio and the University of Pennsylvania’s Gene Therapy Program, exclusive worldwide rights for further development and commercialization were granted to GEMMA Biotherapeutics in August 2024[1][3][6][9].