What is the dosage of adenovirus (AAV rh74)-based gene therapy?

Adenovirus (AAV rh74)-based gene therapy (delandistrogene moxeparvovec-rokl) is a one-time intravenous injection of gene therapy suitable for the treatment of patients with Duchenne Muscular Dystrophy (DMD) who carry specific mutations. The method of administration is intravenous infusion (IV), which usually needs to be carried out in professional medical institutions to ensure the safety and standardization of treatment. This therapy is currently only approved by the FDA for use in children 4 to 5 years old with DMD, and the patients must not have received AAV rh74 virus serotype exposure to avoid existing antibodies affecting the therapeutic effect.

In terms of dosage, the recommended dose is 1.33×10¹⁴ vg/kg body weight, that is, the number of viral gene vectors is accurately calculated based on the patient's weight. This dose is designed to achieve adequate microdystrophingene delivery efficiency while avoiding excessive immune response and organ burden. The entire infusion process generally lasts from 1 to 2 hours and needs to be strictly monitored by a doctor. Before administration, patients typically receive a period of corticosteroid pretreatment to reduce the immune system's attack on the AAV vector, improve efficacy and reduce the incidence of side effects.

Immunosuppression management before and after treatment is a key link. Patients need to start taking hormonal drugs (such as prednisone) about 11 day before the infusion, and usually need to continue taking the drugs for several weeks or even longer during the entire treatment cycle. During treatment, doctors will regularly monitor liver function, blood routine, heart function and other indicators, paying special attention to changes in transaminase levels such as ALT/AST. If severe immune reactions or abnormal liver function occur, the medication regimen may need to be adjusted or the duration of hormone use may need to be extended.

It should be emphasized that delandistrogene moxeparvovec-rokl is not suitable for all DMD patients. Genetic testing and antibody screening must be performed before use to ensure that the patient has AAV rh74Adaptation basis for vectors. In addition, administration can only be done in experienced medical centers equipped with first aid and postoperative observation capabilities. The patient's family should cooperate with the doctor to develop a personalized treatment plan and conduct regular follow-up visits to evaluate the treatment effect and long-term safety.

References:

https://www.fda.gov/drugs/drug-approvals-and-databases/delandistrogene-moxeparvovec-rokl