Homology Medicines Presents Preclinical Data Supporting Immunosuppression Regimen in Ongoing PKU and Hunter Syndrome Clinical Trials, and Details Optimized MLD Gene Therapy Candidate at the 19th Annual WORLDSymposium™ Meeting
Preclinical Studies Demonstrated a Targeted Immunosuppression Approach Led to Reduced Immune Response to
“We are pleased to share our work outlining the impact immunosuppression regimens had on outcomes following AAVHSC dosing in NHPs, as it contributes to a key area of research in the gene therapy and gene editing field,” stated
Details of Homology’s Presentations at WORLDSymposium™
In the poster titled, “Tacrolimus Administration in Combination with Dexamethasone Reduces Neutralizing Antibody Formation Against AAV Vector and Increases Transgene Expression in Cynomolgus Macaques,” data showed that administration of the T-cell inhibitor tacrolimus with dexamethasone in AAVHSC-PAH-treated non-human primates (NHPs) resulted in:
- Lowered secretion of inflammatory cytokines and activation state of CD8+ T cells compared to the no immunosuppression (IS) group;
- Reduced AAVHSC neutralizing antibody (nAb) formation compared to NHPs treated with each agent alone and by 4.8-fold compared to the no
- Increased PAH gene expression, as measured by mRNA, compared to each agent alone and by two-fold compared to the no
In the poster titled, “Gene Therapy for Metachromatic Leukodystrophy: Lead Candidate Optimization,” a single I.V. administration of optimized HMI-204 in the murine model of MLD showed:
- Systemic and central nervous system (CNS) biodistribution, including robust expression in the CNS;
- Human ARSA cellular expression patterns in the brain that were nearly identical to that of murine Arsa distribution in wildtype age-matched controls; and
- Sustained levels of ARSA activity reaching normal adult ARSA brain activity levels.
Additionally, packaging productivity of HMI-204 demonstrated a substantial improvement in vector genome yields, compared to the earlier MLD gene therapy candidate.
For more information, please visit the Publications and Presentations page on Homology’s website.
About Metachromatic Leukodystrophy (MLD)
MLD is a rare lysosomal storage disorder primarily caused by a mutation in the ARSA gene. ARSA is responsible for the creation of the arylsulfatase A (ARSA) protein, which is required for the breakdown of sulfatides in cells. In MLD, sulfatides accumulate and destroy myelin-producing cells in the peripheral and central nervous systems leading to progressive and serious neurological deterioration. The late infantile form of the disorder is estimated to affect 1 in 40,000 people, and it is fatal within 5-10 years after onset.
About Homology Medicines, Inc.
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