Large-scale discovery of Duchenne muscular dystrophy biomarkers published

5/26/2015

The results of a collaborative study by a large group of academic, industry and patient advocacy scientists to address the critical need for useful biomarkers to help with the diagnosis and treatment of Duchenne muscular dystrophy was published today in the Early Edition of the Proceedings of the National Academy of Sciences USA (PNAS). Using the SOMAscan assay to measure 1,125 proteins simultaneously in the blood of Duchenne patients and age-matched controls, the research group identified highly significant changes in the concentration levels of 44 different proteins. These findings are being shared openly with the entire Duchenne research and patient advocate community in the hope of driving further understanding of Duchenne biology, as well as accelerating new diagnostic and therapeutic development.

“Although we have known the genetic cause of Duchenne since the mid 1980s, progress towards effective treatments has been painfully slow, largely because we don’t have the biomarkers we need to quickly test promising new treatments or to provide a set of diagnostic and prognostic tests for each Duchenne patient,” said Pat Furlong, Founding President of Parent Project Muscular Dystrophy (PPMD) and an author of the PNAS study. “This work is an important and exciting step toward closing that gap.”

Using a new protein measurement technology from SomaLogic, blood samples from two different cohorts of Duchenne patients and non-Duchenne control volunteers (usually siblings of the Duchenne patients) were analyzed independently, and the results compared between the cohorts. Forty-four different proteins were found to be either highly increased (24 proteins) or decreased (20 proteins) in the Duchenne samples as compared to controls. While several of these protein changes have been previously described (usually related to the breakdown of muscle tissue and leakage into the blood stream), many of the other proteins discovered using this new approach were unexpected, and not previously associated with Duchenne. Furthermore, the majority of the protein concentrations observed varied widely with the age of the patient, and thus with the progressive severity of the disease.

“We are excited by the findings of this study, and are already pursuing some of the new leads that emerge from it,” said Yetrib Hathout, Associate Professor in the Department of Integrative Systems Biology, Center for Genetic Medicine at Children’s National Health System and first author on the PNAS paper. “These non-invasive biomarkers potentially can be used as readout to monitor disease progression and response to therapies in boys with Duchenne, and should also spur a large number of renewed efforts around finding new treatments for this devastating disease.”

The 1,125 proteins were measured using the “SOMAscan™ assay,” a technology developed by SomaLogic that can simultaneously and accurately measure the individual proteins in very small amounts of blood or other samples. By comparing patient and control samples, identification of critical differences in protein concentrations can be identified rapidly. These significantly different proteins can then be used as the basis for developing new diagnostic and therapeutic approaches, including their use as biomarkers for quickly assessing the efficacy of promising new drugs.

“This kind of study is precisely what we envisioned when we set out to discover and develop a new approach to protein measurement,” said Larry Gold, Founder and Chairman of SomaLogic and senior author on the PNAS paper. “We are thrilled to be a part of this important step towards improving the lives of Duchenne patients and their families, and look forward to expanding on these findings in collaboration with these and additional partners. We also hope that other researchers and advocacy groups will join forces with us to bring this powerful technology to bear on a wide range of rare diseases.”

About Duchenne muscular dystrophy

Duchenne muscular dystrophy is the most common fatal genetic disorder diagnosed in childhood, affecting approximately 1 in every 3,500 to 5,000 live male births (about 20,000 new cases each year). Because the Duchenne gene is found on the X-chromosome, it primarily affects boys; however, it occurs across all races and cultures. Duchenne results in progressive loss of strength and is caused by a mutation in the gene that encodes for dystrophin. Because dystrophin is absent, the muscle cells are easily damaged. The progressive muscle weakness leads to serious medical problems, particularly issues relating to the heart and lungs. Young men with Duchenne typically live into their late twenties. Learn more at the PPMD website.