MECP2 Duplication Syndrome
Conditions
Keywords
MECP2, dupMECP2, CNS, neurodevelopmental disease, Gene-editing, HG204, CRISPR, MDS
Brief summary
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.
Interventions
GENETICHG204
The study will enroll up to 2 cohorts, evaluating a starting dose plus a higher or lower dose
Sponsors
Peking University First Hospital
HuidaGene Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, multiple doses of a single intracerebroventricular injection of HG204
Eligibility
Sex/Gender
MALE
Age
2 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of systemic adverse events | 52 weeks | Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Clinical Global Impression Scale | 52 weeks | Clinical Global Impression Scale is a scale to evaluate mental disorder severity, with a score range from 1-7, the higher scrore means worse mental disorder. |
| Change from baseline in Griffiths Developmental Assessment Scale | 52 weeks | Griffiths Developmental Assessment Scale is a scale to evaluate mental development function of children aged 0-8, including sensory, cognitive and movement, the minimum score is 0, and no maximum limit for the highest score, the higher score means better mental development. |
| Change from baseline in Peabody Developmental Assessment Scale | 52 weeks | Peabody Developmental Assessment Scale is a scale to evaluate motor function of children aged 0-6, with a score range from 0-100, the higher scrore means better motor function. |
| Change from baseline in Wechsler (toddler/child) Intelligence Scale (fourth version) score | 52 weeks | Wechsler (toddler/child) Intelligence Scale (fourth version) score is a scale to assessing the intelligence of children aged 6 to 16, the score range showed a normal distribution, there is no minimum and maximum score, score from 90 to 110 points is normal intelligence result, the higher score means better intelligence. |
| Adaptive Behavior Rating Scale | 52 weeks | Adaptive Behavior Rating Scale is a scale assessing daily living ability of children aged 0-18, with a score range from 0-200, the higher score means better daily living ability |
Countries
China
Contacts
Primary ContactStudy Director
Outcome results
None listed