Prosensa publishes a sensitive, reproducible and objective methodology for dystrophin analysis in patients with Duchenne muscular dystrophy

Leiden, The Netherlands, Sept. 24, 2014 (GLOBE NEWSWIRE) — Prosensa Holding N.V. (NASDAQ: RNA), the biopharmaceutical company focusing on RNA-modulating therapeutics for rare diseases with high unmet need, today announced that the results of its research into developing an accurate and reproducible method for the measurement of dystrophin in patients with Duchenne muscular dystrophy (DMD) and Becker’s muscular dystrophy (BMD) have been published in the online peer reviewed journal PLOS ONE (
The publication, by Chantal Beekman et al from Prosensa, describes the Company’s semi-automated image analysis method, which was shown to be objective (operator independent), reproducible (in multiple samples and experiments) and sensitive for assessing dystrophin levels by immunofluorescence in muscle biopsies from BMD and DMD patients in natural history studies or clinical studies with compounds aiming to restore dystrophin expression.
This method has also been tested as part of an international consortium initiative, the Biochemical Outcome Measures study group, which focuses on the optimization of dystrophin assays.
DMD is characterized by the absence or reduced levels of dystrophin expression on the inner surface of the sarcolemmal membrane of muscle fibers. Clinical development of therapeutic approaches aiming to increase dystrophin levels requires sensitive and reproducible measurement of differences in dystrophin expression in muscle biopsies of treated patients with DMD. This, however, poses a technical challenge due to donor variance in the occurrence of revertant fibers and low trace dystrophin expression throughout the muscle fibers in the DMD biopsies.
As dystrophin expression is variable between muscle groups and even within the same muscle, demonstration of a pharmacodynamic effect requires comparison of two biopsies pre- and post-treatment, taken from the same muscle, and sampled from areas of similar disease state. Furthermore, determining intensity of individual fibers and its distribution across the biopsy yields a more informative and objective measure of dystrophin expression than counting fibers.
“This innovative methodology, which has been developed by Prosensa, underscores our scientific commitment to understanding DMD and developing treatments for this devastating disease. We are pleased to share these developments with the scientific community as it should help support the DMD research field by enabling enhanced clinical trial protocols with more objective and representative measures of dystrophin. While this methodology is an important step forward in understanding dystrophin expression, challenges remain due to variability in the muscle. Clinical outcome measures, such as the six-minute walk test (6MWT), continue to be the optimal measurement of a drug’s efficacy in DMD,” explained Dr. Giles Campion, Prosensa’s Chief Medical Officer and Senior Vice-President R&D.

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