Shanghai-based HuidaGene Therapeutics has announced the first subject dosing of the HERO clinical trial, which is evaluating HG204, an RNA-editing therapy, for the treatment of MECP2 duplication syndrome (MDS).
CRISPR RNA-Editing Therapy and Its Mechanism
The CRISPR RNA-editing therapy utilizes a single adeno-associated virus vector to deliver HuidaGene’s proprietary high-fidelity RNA editor, hfCas13Y, along with a guide RNA targeting the MECP2 gene. This approach aims to reduce MECP2 mRNA and protein levels, which are overexpressed due to the genomic duplication of the Xq28 region. Preclinical studies have shown that HG204 is stably and durably expressed in the brain tissue of mice and monkeys, with a single intracerebroventricular injection leading to significant improvements in motor skills, social behavior, and survival time in humanized mouse models of MDS.
Understanding MECP2 Duplication Syndrome (MDS)
Methyl-CpG binding protein 2 (MeCP2) duplication syndrome (MDS) is a rare and fatal neurodevelopmental disorder caused by the duplication of the MECP2 gene, leading to an overexpression of the MeCP2 protein, an epigenetic regulator crucial for normal brain development and function. Symptoms of MDS include infantile hypotonia, severe intellectual disability, developmental delays, epilepsy, recurrent respiratory infections, loss of motor and speech skills, anxiety, and a shortened lifespan. MDS primarily affects males, with an estimated 50,000 to 100,000 cases worldwide, and approximately half of the patients do not survive past the age of 25. Currently, there are no approved disease-modifying therapies for MDS, and treatment options are limited to supportive care.
HG204’s Regulatory Designations and Potential Impact
HG204 has previously earned Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPDD) in the US, and ODD status from the European Medicines Agency (EMA). These designations highlight the potential impact of HG204 as a novel treatment option for MDS and underscore the urgency of developing effective therapies for this rare and devastating disorder.
