Background: Adeno-associated virus (AAV) based gene therapies are emerging in Duchenne muscular dystrophy (DMD). Exposure to wild-type AAV can lead to development of neutralizing antibodies (NAbs) and block AAV transduction, thereby limiting the delivery of AAV vector-based gene therapy.
Objective: To study the seroprevalence of anti-AAV 2 and 9 NAbs among boys with DMD followed at the MDA care center clinic in Atlanta, Georgia.
Results: We prospectively enrolled 89 boys with DMD (median age 10.5 years, range 2-20 years, 59% ambulatory, 54% on steroids) from June 2016 to July 2020. All study participants had a confirmed pathogenic mutation in the dystrophin gene (73%, n=65, out of frame deletion, 20%, n=18, point mutation and 7%, n=6, duplication). Ethnic background of the study participants was as follows: Caucasians 48% (43/89), Hispanics 29% (26/89), African Americans 18% (16/89) and Southeast Asian 4% (4/89). AAV neutralizing titers were reported as the estimated dilution at which 50% of AAV infection has been inhibited (IC50). Low, moderate and high positive Nab titers were defined as <1:20, 1:20-1:240 and >1:240. Fifty-four percent (n=48/89) of the study participants had anti-AAV 2 and 9 NAbs. Seroprevalence of anti-AAV 2 and 9 NAbs were highest among African Americans 63% (10/16) followed by Hispanics 54% (14/26), Caucasians 51% (22/43) and Southeast Asian Indians 50% (2/4). There was no difference in the NAbs seroprevalence between ambulatory (52%, n=25) versus non-ambulatory (48%, n=23), and steroid exposed (52%, n=25) versus naïve (48%, n=23) patients.
Conclusions: Recent work by Khatri et al., 2021, showed an unexpected increased incidence of AAV NAbs among healthy Black and Hispanic donors. In our study, the anti-AAV 2 and 9 NAbs seroprevalence was highest among African American and Hispanic boys with DMD. To best of our knowledge, this is the first study recording the ethnic background and anti-AAV NAbs seroprevalence status in boys with DMD. Study limitations include limited AAV serotypes analyzed (only AAV 2 and 9), unable to measure total binding antibodies, lack of a control arm and a single-center experience.
Acknowledgement: Raj Razdan, MS, Research coordinator, Children's Healthcare of Atlanta, Atlanta, GA and the Atlanta MDA/ DMD families.
Funding: Children's Healthcare of Atlanta Foundation.