Large-scale analysis of blood-based protein biomarkers for Duchenne muscular dystrophy published

Collaboration between patient advocates, academic researchers, and industry scientists provides deeper knowledge of Duchenne biology and potential new approaches to diagnosis and treatment

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Parent Project Muscular Dystrophy (PPMD)

May 26, 2015, 08:15 ET

HACKENSACK, N.J. and BOULDER, Colo. , May 26, 2015 /PRNewswire-USNewswire/ -- 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 is published this week in the Early Edition of the Proceedings of the National Academy of Sciences USA (PNAS). Using a novel approach 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
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.

About Parent Project Muscular Dystrophy

Parent Project Muscular Dystrophy (PPMD) is the largest most comprehensive nonprofit organization in the United States focused on finding a cure for Duchenne muscular dystrophy—our mission is to end Duchenne.

We invest deeply in treatments for this generation of young men affected by Duchenne and in research that will benefit future generations. We advocate in Washington, DC, and have secured hundreds of millions of dollars in funding. We demand optimal care, and we strengthen, unite and educate the global Duchenne community.

Everything we do—and everything we have done since our founding in 1994—helps boys with Duchenne live longer, stronger lives. We will not rest until every young man has a treatment to end Duchenne. Go to www.ParentProjectMD.org for more information or to learn how you can support our efforts and help families affected by Duchenne.

About SomaLogic
SomaLogic is transforming healthcare by applying our proprietary protein-measurement technology to the development of new diagnostic tests that deliver a higher quality of life by detecting diseases at their earliest stages and monitoring general wellness. Our ultimate goal is the "Wellness Chip," a single cost-effective and reliable blood test for multiple diseases and conditions that will enable healthcare providers to precisely monitor each individual's state of health and wellness in real time.

Our technology also has multiple potential applications in both life sciences and therapeutics, and it is now available to the entire biomedical scientific community for their own research needs.

For more information, visit www.somalogic.com

Full paper citation: Available Tuesday, May 26, 2015 at: http://www.pnas.org/cgi/doi/10.1073/pnas.1507719112

Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy

Contributing authors: Yetrib Hathout^a, Ed Brody^b, Paula Clemens^c, Linda H. Cripe^d, Robert Kirk DeLisle^b, Pat Furlong^e, Heather Gordish-Dressman^a, Lauren Hache^a, Erik Henricson^f, Eric P. Hoffman^a, Yvonne M. Kobayashi^g*, Angela Lorts^h, Jean K. Mahⁱ, Craig McDonald^f, Bob Mehler^b, Sally Nelson^j, Malti Nikrad^b, Britta Singer^b, Fintan Steele^b, David Sterling^b, H. Lee Sweeney^k, Steve Williams^b, and Larry Gold^b.

Affiliations:
^aResearch Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20012, USA
^b SomaLogic, Inc., Boulder, CO 80301
^cNeurology Service, Pittsburgh VA Healthcare System, Pittsburgh, PA 15240 and University of Pittsburgh, Pittsburgh, PA 15213
^dThe Heart Center, Nationwide Children's Hospital, The Ohio State University, Columbus, OH 15213 USA
^eParent Project Muscular Dystrophy, Hackensack, NJ 07601 USA
^fDepartment of Physical Medicine and Rehabilitation, University of California, Davis School of Medicine, Davis, CA 95618, USA
^g Indiana University School of Medicine, Department of Cellular and Integrative Physiology, Indianapolis, IN 46202
^hThe Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 USA
ⁱDepartment of Pediatrics, University of Calgary, Alberta Children's Hospital, Calgary, AB, Canada T3B 6A8.
^j Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Aurora, CO 80045 USA
^k Department of Pharmacology & Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610
* Employed by Eli Lilly and Company, Indianapolis, IN 46285 USA, since Oct 2012