Use of plasmapheresis to lower anti-AAV antibodies in nonhuman primates with pre-existing immunity to AAVrh74
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View abstract on PubMed
Summary
This summary is machine-generated.Plasmapheresis effectively reduces anti-adeno-associated virus (AAV) antibodies in nonhuman primates, enabling gene transfer therapy. This pretreatment is safe and may allow redosing or overcoming pre-existing immunity in future human studies.
Area Of Science
- Biomedical research
- Gene therapy
- Immunology
Background
- Pre-existing immunity to adeno-associated virus (AAV) prevents patients from receiving gene transfer therapies.
- Developing strategies to overcome AAV immunity is crucial for expanding gene therapy accessibility.
Purpose Of The Study
- To investigate immunosuppression strategies for AAV gene transfer therapy safety and efficacy.
- To evaluate plasmapheresis as a method to circumvent pre-existing AAV immunity or enable redosing.
Main Methods
- Nonhuman primates received delandistrogene moxeparvovec (SRP-9001) gene therapy.
- Different immunosuppression regimens (prednisone, rituximab, sirolimus) were tested.
- Plasmapheresis was performed before redosing in select cohorts to assess its impact on anti-AAV antibodies.
Main Results
- Plasmapheresis successfully reduced circulating anti-AAVrh74 antibodies after 2-3 exchanges.
- Redosing after plasmapheresis was well-tolerated without adverse clinical or immunological events.
- A cohort redosed without plasmapheresis experienced hypersensitivity reactions, which were managed.
Conclusions
- Plasmapheresis is a safe and effective pretreatment to lower anti-AAV antibody levels in nonhuman primates.
- This approach shows promise for enabling gene transfer therapy in individuals with pre-existing immunity or requiring redosing.
- Findings may guide human clinical trials for AAV-based gene therapies.
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