A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)

NCTID	NCT06615206 (View at clinicaltrials.gov)
Description	Methyl-CpG binding protein 2 (MECP2) is a dosage-sensitive, X-linked gene critical for central nervous system development and functional maintenance, which gain-of-function causes MECP2 duplication syndrome (MDS). Affecting primarily in males, this disorder is characterized by severe intellectual disability, motor dysfunction, infantile hypotonia, epilepsy, respiratory tract infections, and premature death before 25 years of age with no curative therapy. HG204 is a CRISPR RNA-editing therapy packaging novel high-fidelity Cas13Y (hfCas13Y) technology, using one single adeno-associated virus (AAV) vector to target and knock down MECP2 mRNA in the brain. Preclinical studies showed that a single intracerebroventricular injection of HG204 persistently decreased MECP2 mRNA and MECP2 protein in the cortex of the MDS mice, reversed the abnormal motor and social phenotypes, and significantly prolonged survival in MDS mouse models. (Show More)
Development Status	Active
Indication	MECP2 Duplication Syndrome
Disease Ontology Term	DOID:0060799
Compound Name	HG204
Sponsor	HuidaGene Therapeutics Co., Ltd.
Funder Type	Industry
Recruitment Status	Recruiting (Click here for study contact information)
Enrollment Count	6 (ESTIMATED)
Results Posted	Not Available

Target Gene/Variant	MECP2
Therapy Type	Gene editing
Therapy Route	In-vivo
Mechanism of Action	Gene inactivation
Route of Administration	Intracerebroventricular
Drug Product Type	Viral vector
Delivery System	Viral transduction
Vector Type	AAV
Editor Type	hfCas13Y
Dose 1	Up to 2 dose cohorts, undisclosed concentration

Eligible Age	2 Years - 18 Years
Standard Ages	Child, Adult
Sexes Eligible for Study	MALE
Eligibility Criteria	Inclusion Criteria: * Males ≥ 2 and ≤18 years at the time of signing informed consent; * Genetic test and clinical confirmed diagnosis of MDS; * Stable pattern of seizures, or has had no seizures while currently receiving medical treatment (including antiepileptics) and physical therapy are stable for at least 2 months before screening; * Willing to adhere to protocol, including biological samples collection and hospitalization for intracerebroventricular injection surgery; * Acceptable hematology, clinical chemistry, and urine laboratory parameters. Exclusion Criteria: * MECP2 gene triplication; * Concurrent genetic syndromes other than MDS; * Significant brain or cerebellar atrophy, or other significant degenerative changes as shown in cranial MRI at screening; * Prior or current hypertension, cardiomyopathy, myocardial ischemia or atrial fibrillation and other cardiovascular diseases; * Prior central nervous system surgery within 6 months before enrolment; * Systemic use of immunosuppressive drugs within 3 months before enrolment; * Prior gene therapy or oligonucleotide therapy treatments; * Any other conditions that would not allow the potential subject to complete follow-up examinations during the study and would, in the opinion of the investigator, make the potential subject unsuitable for the study. View Inclusion and Exclusion Criteria at ClinicalTrials.gov

No.of Trial Sites	1
Locations	China

Has US IND	False
FDA Designations	Orphan Drug Designation, Rare Pediatric Disease Designation
Recent Updates	First patient dosed announced in December 2024