New to MyHealth?
Manage Your Care From Anywhere.
Access your health information from any device with MyHealth. You can message your clinic, view lab results, schedule an appointment, and pay your bill.
ALREADY HAVE AN ACCESS CODE?
DON'T HAVE AN ACCESS CODE?
NEED MORE DETAILS?
MyHealth for Mobile
Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice
Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice EMBO MOLECULAR MEDICINE Annoni, A., Cantore, A., Della Valle, P., Goudy, K., Akbarpour, M., Russo, F., Bartolaccini, S., D'Angelo, A., Roncarolo, M. G., Naldini, L. 2013; 5 (11): 1684-1697Abstract
A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50-100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because of memory B-cell depletion in response to constant exposure to high doses of FIX. Regulatory T cells displaying FIX-specific suppressive capacity were induced in gene therapy treated mice and controlled FIX-specific T helper cells. Gene therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by repeated high-dose FIX protein administration, which induced severe anaphylactoid reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus reverse pre-existing immunity, induce active tolerance to FIX and establish sustained FIX activity at therapeutic levels. These data position gene therapy as an attractive treatment option for inhibitors-positive haemophilic patients.
View details for DOI 10.1002/emmm.201302857
View details for Web of Science ID 000326463300004
View details for PubMedID 24106222