Homology Medicines, Inc. announced the details of HMI-204, its optimized, in vivo, one-time gene therapy product candidate for the treatment of metachromatic leukodystrophy. Following a single I.V. administration in the MLD murine model, the candidate crossed the blood-brain-barrier to the central nervous system and reached key peripheral organs involved in MLD. As a rare and often fatal genetic disorder, efforts are underway in the U.S. and globally to implement prospective newborn screening for MLD.

Homology is actively seeking a partner to advance this preclinical-stage candidate. In the murine model of MLD, a single I.V. administration of the optimized gene therapy candidate, which uses one of Homology's proprietary AAVHSC capsids, resulted in: Broad biodistribution to peripheral organs and the CNS; Expression of human ARSA levels in multiple brain regions and cell types, which were well-above the minimum levels of enzyme needed to correct the MLD disease phenotype; hARSA activity levels in the brain that are predictive of functional improvements; and hARSA activity in the serum. Additionally, optimizations led to significant improvements in vector yield and superior packaging for the candidate.