Senior investigator, Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke/National Institutes of Health

Carsten G. Bönnemann, MD

“Only by coming together with all the sponsors and everyone who is in the trials, were we able to quickly compare the genotypes, compare the events, confirm that the events are strikingly similar in that clinical evolution, that the genotypes are really similar as well. And that lead to identification of the likely offending immunological epitope on that transgene.”

Investigators have elucidated at-risk genotypes for anti-transgene serious adverse events (SAEs) shared across studies of Duchenne muscular dystrophy (DMD) gene therapies by 4 sponsors, Pfizer, Sarepta, Genethon, and Solid Biosciences.

The group’s findings were presented at the 

American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting, May 16-19, 2022

, in Washington, D.C., by Carsten Bonnemann, MD, senior investigator, Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke/National Institutes of Health.

Bönnemann and colleagues hypothesize that patients’ genotypes determine a T-cell mediated immune response to the expressed transgene protein in a cross-reactive immunological material (CRIM)-negative setting. CGTLivespoke with Bönnemann to learn more about the group’s findings as well as their impact on trials investigating DMD gene therapies.

Bönnemann CG, Belluscio BA, Braun S, et al. A collaborative analysis by clinical trial sponsors and academic experts of anti-transgene SAEs in studies of gene therapy for DMD. Presented at: ASGCT 25th Annual Meeting, May 16-19, 2022; Washington DC.

Videos

The senior investigator from NINDS discussed findings investigating serious AEs across different trials. 

Carsten G. Bönnemann, MD

Articles

Carsten Bönnemann, MD, on Identifying At-Risk Genotypes for DMD Gene Therapy