Prevalence of anti-HLA antibodies in Duchenne Muscular Dystrophy patients at screening visit and after intra-bone administration of DT-DEC01 therapy


Clinical Trials

Poster Number: 111


Maria Siemionow, MD,PhD, Dystrogen Therapeutics Corp., Jacek Wachowiak, MD, PhD, Department Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Grzegorz Bieganski, MD, Poznan University of Medical Sciences, Jaroslaw Czarnota, MD, Medpolonia Hospital, Poznan, Adam Niezgoda, MD, PhD, Department of Neurology, Poznan University of Medical Sciences, Krzysztof Siemionow, MD, PhD, Dystrogen Therapeutics Corp., Ahlke Heydemann, PhD, University of Illinois

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.