Webinar: Dystrophin Quantification in Preclinical and Clinical Settings

Duchenne muscular dystrophy is caused by mutations in the dystrophin encoding DMD gene that disrupt the reading frame. Muscle fibers lacking dystrophin are more sensitive to damage and over time muscle tissue and muscle function is progressively lost resulting in wheelchair dependency around age 10 and premature death in the 2nd to 4th decade of life. Mutations that maintain the reading frame allow the production of internally deleted partially functional dystrophins. These mutations are associated with the later onset, less progressive Becker muscular dystrophy. This reading frame rule forms the premise of current dystrophin restoring therapies, such as exon skipping to allow Duchenne patients to produce Becker-type dystrophin and gene therapy aiming to deliver a micro-dystrophin transgene to muscles.

In this lecture, you will learn the different approaches, considerations to the question of how much dystrophin is enough, how to measure this in the clinical trial settings, and how we employed the ProteinSimple capillary immunoassay for analyzing dystrophin in our preclinical studies.

Learning Objectives

• Summarize the criteria for clinically relevant dystrophin restoration.
• Assess the methods for quantifying dystrophin restoration in clinical and pre-clinical settings.
• Explain how Simple Western™ is used for reproducible dystrophin quantification.

Speaker

Annemieke Aartsma-Rus, PhD
Professor of Translational Genetics at Leiden University Medical Center

Biography

Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics at the Department of Human Genetics of the Leiden University Medical Center. Her work currently focuses on developing antisense-mediated exon skipping as a therapy for Duchenne muscular dystrophy and rare brain diseases. Dr. Aartsma-Rus aims to bridge the gap between stakeholders (patients, academics, regulators and industry) involved in drug development for rare diseases and to develop exon skipping therapies for patients with unique mutations. She has published over 230 peer-reviewed papers, 11 book chapters and 15 patents, and has given many invited lectures at scientific conferences and patient organization meetings. Dr. Aartsma-Rus has received numerous awards, including the Duchenne Award from the Dutch Duchenne Parent Project, Black Pearl Science Award from Eurordis, Ammodo Science Award, and outstanding achievement award from the Dutch Society of Gene and Cell Therapy, for her contributions to the muscular dystrophy field. In 2020, Dr. Aartsma-Rus co-founded the Dutch Center for RNA Therapeutics (DCRT), a non-for-profit academic collaboration aiming to develop clinical treatment with exon skipping therapies for eligible patients with unique mutations.

Dr. Aartsma-Rus is chair of the TREAT-NMD Advisory Committee for Therapeutics (TACT), Chair of the Dutch Center for RNA Therapeutics, Vice-Chair of COST Action CA17103 (Delivery of antisense RNA therapies), board member of the N-of-1 Collaborative, was President of the Oligonucleotide Therapeutics Society (2019-2021), and was Chair of the TREAT-NMD executive committee (2013-2016 and 2019-2020). In addition, she is a member of the Therapies Scientific Committee of the International Rare Disease Research Consortium (IRDiRC). Dr. Aartsma-Rus is co-editor in chief of Nucleic Acid Therapeutics, and serves on multiple editorial boards, e.g. Journal of Neuromuscular Diseases (associate editor), Molecular Therapy and Therapeutic Advances in Rare Disease.