Duchenne muscular dystrophy (DMD) is a lethal X-linked disease, caused by mutations of the dystrophin gene leading to progressive muscle degeneration and weakness. A novel DT-DEC01 therapy of Dystrophin Expressing Chimeric (DEC) cells was created by fusion of human myoblasts derived from normal (allogeneic) and DMD-affected (autologous) donors. In allogenic therapies, it is important to determine the strength and specificity of HLA antibodies and reactivity with specific donors.
This study assessed prevalence of anti-HLA antibodies in DMD patients at screening visit and after DT-DEC01 administration.
Pilot, open label study. Intra-bone marrow (systemic) administration of a single dose of DT-DEC01 therapy (2 – 4 x10^6 cells / kg) in 5-18 years old boys (n = 4) with DMD and negative anti-HLA antibodies (Bioethics Committee approval no.185/2022). No immunosuppression was used.
During screening visit, 11 DMD patients were tested for presence of anti-HLA antibodies by Luminex panel reactive antibody assay for presence of class I, class II and MICA anti-HLA Ab. If Anti-HLA test was positive, further screening assessed presence of Donor Specific Antibodies (DSA).
Six of 11 DMD patients (54,5%) screened positive for anti-HLA antibodies. Presence of anti-HLA Class I antibodies was confirmed in 3/6 patients, where 1 patient was positive for DSA (donor father) Presence of anti-HLA Class II antibodies was detected in 4/6 patients and 2 patients screened positive for DSA (donor father) and in 3/6 patients, autoantibodies were detected.
Screening for anti-HLA antibodies was negative in patients treated with DT-DEC01 and no immune response was observed for up to 12 months after intra-bone administration of DT-DEC01 therapy.
This study confirmed high (54,5%) prevalence of anti-HLA antibodies in DMD patients. In patients with baseline negative anti-HLA antibody tests treated with intra-bone marrow administration of DT-DEC01, subsequent screening revealed long-term negative anti-HLA antibodies, confirming immunomodulatory but not immunogenic effect of DT-DEC01 therapy.