New gene therapy trial hopes to tame rare metabolic disease in kids

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Subjects must be ≤ 6 years; 2. History of diagnosis of GA-I, and confirmed by gene mutation analysis with biallelic GCDH mutation; 3. At the time of screening, there was one of the obvious neurological manifestations associated with the following diseases, including macrocephaly, dystonia, and motor/intellectual development Poor fertility, epilepsy, abnormal EEG; 4. Those who are receiving standard treatment recommended by the guidelines and whose symptoms remain poorly controlled by the investigator; 5. Plasma GA and 3-OHGA levels were higher than the normal range during screening; Exclusion Criteria: 1. Participation in gene therapy or stem cell transduction therapy at any time prior to screening for this trial or participation in any other clinical trial within 3 months prior to screening; 2. Recurrent seizures that are not suitable for surgery, based on Investigator judgment; 3. Current severe liver or kidney or cardiovascular disease or coagulation dysfunction, autoimmune deficiency, or uncontrolled autoimmune disease or need immunosuppressive long-term treatment, poorly controlled diabetes (HBA1C ≥7% at screening) or high blood pressure; 4. Active viral infection (includes HIV or serology positive for hepatitis B or C or syphilis); 5. Presence or history of malignancy; 6. Received systemic immunosuppressive therapy within 3 months prior to screening; 7. Received vaccine within 4 weeks prior to administration or plan to receive vaccine within 1 year after administration; 8. Plan to receive surgery during the study; 9. Current using medications including, drugs, herbal or OTC medications that strongly inhibit or induce CYP3A4 or P-glycoprotein (P-gp), e.g., metoclopramide, grapefruit juice, ketoconazole, erythromycin; 10. Abnormal brain structure, not suitable for lateral ventricle administration; 11. Abnormal laboratory test results, which are judged by the investigator not suitable for surgery; 12. History of systemic hypersensitivity reaction to investigational product, the excipients contained in the formulation, or prophylactic immunosuppressant; 13. Contraindicated use of corticosteroids and sirolimus; 14. Contraindicated with general anesthesia or sedation; 15. As judged by the investigator, unable to perform lateral ventricle puncture or Ommaya capsule implantation or lumbar puncture; 16. Unable to perform CT or MRI; 17. Poor compliance; 18. Any other situation where, judged by the investigator, the subject is not suitable for participating in this study.