Researchers develop a novel method for diagnosing Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a rapidly progressive form of muscular dystrophy caused by a mutation in the DMD gene, the largest known human gene. It affects approximately 1 in 3500 male births worldwide. Individuals with DMD have a progressive loss of skeletal muscle function followed by severe muscle wasting and weakness.

By age 12 most boys are confined to a wheelchair with few individuals living beyond their 30s. Secondary problems arise from excessive skeletal muscle degeneration, including cardiomyopathy (enlarged heart) and breathing complications, which are the most common causes of death.

Early detection of DMD is imperative as the earlier the disease is detected, the better opportunity the individual has for seeking treatments to slow this progression. Current methods for diagnosing DMD are often laborious, expensive, invasive, and typically diagnose the disease late in its progression. Skeletal muscle degenerates in Duchenne muscular dystrophy (DMD). Hematoxylin and Eosin (H&E) staining of Tibialis Anterior (TA) muscle sections from 3- and 12-month-old control (A, C) and DMD model MDX (B, D) mice are shown here.

The 3-month old control muscle section shows normal fibre morphology including circular shape and absent central nuclei (A), whereas 3-month old MDX mice show muscle degeneration denoted by muscle fibres with central nuclei with a smaller diameter (yellow arrows), atrophied muscle (black arrow), and more prevalent nuclei of inflammatory cells (B).

Muscle degeneration is much more dramatic in older MDX muscle, as evident by the absence of normal muscle fibre structure and presence of fatty and necrotic tissues (green arrows).

A group of researchers from the RNA Institute at the University at Albany, led by Drs. Igor Lednev and Bijan Dey, have developed a novel method for diagnosing DMD which could improve the accuracy, ease and potential of an early diagnosis.

Findings were published in the journal Nature Scientific Reports and titled “Diagnosis of a model of Duchenne muscular dystrophy in blood serum of MDX mice using Raman hyperspectroscopy“.

The team also consisting of The RNA Institute scientist Paromita Dey, graduate student Nicole Ralbovsky and undergraduate researcher Andrew Galfano.

The novel method analyzes blood serum by combining Raman hyperspectroscopy with advanced statistical analysis and has had 100% success classifying mouse models used to study DMD.

Raman spectroscopy (named after the physicist C.V. Raman) is a technique used to determine vibrational modes of molecules and can provide a structural fingerprint by which to identify those molecules. It has shown great potential in diagnosing many diseases including cancer and Alzheimer’s disease.

Because Raman hyperspectroscopy produces a specific fingerprint for each sample, different samples can be distinguished, including dried traces of body fluids collected from healthy donors and from donors with a disease.

By combining this technique with advanced statistical analyses the researchers at the RNA Institute were able to build a model which identifies differences in classes of samples to make accurate, early and minimally invasive diagnostic predictions.

“This research really has great potential to revolutionize how we diagnose ailments, including DMD,” said Nicole.

“Current methods are focused on detecting a specific biomarker or two which can be present at very low concentrations during early stages of the disease. Our method is incredibly advantageous because it probes the entire biochemical composition of the sample, giving us the ability to detect disease earlier and more specifically than any other currently used method.” Lednev Research GroupNicole Ralbovsky, a fourth year graduate student from the Lednev Lab and member of the RNA Fellows program at The RNA Institute, was recently honored with two prestigious awards for her work on Raman Spectroscopy. The NY/NJ section of the 2020 Society for Applied Spectroscopy‘s Graduate Student Award and the Eastern Analytical Symposium Graduate Student Research Award. Dey works with his laboratory scientist and students. Photo by Mark Schmidt.Dey says that DMD is a devastating X-linked muscle degenerative disease that manifests in early childhood. “However, we are lacking easy, affordable, and early detection of the disease. Despite certain limitations, the current treatment options provide patients with symptom relief and improved quality of life if treated early. Our study could solve this long-standing problem.” The major goal of the Dey lab is to understand the fundamental molecular mechanism of muscle development and to devise new therapeutic and diagnostic platforms for DMD. Dr. Dey’s research program is funded by the State University of New York (SUNY), American Heart Association (AHA) and National Institutes of Health (NIH). “This is exciting research that demonstrates the importance of an interdisciplinary team coming together to develop a potentially new diagnostic approach for a common form of muscular dystrophy,” said Dr. Andrew Berglund, Director of the RNA Institute. Future research is required to study this novel detection method within humans but it is clear that this methodology has significant potential for use as a novel technique for diagnosing Duchenne muscular dystrophy in clinical settings. Original research article Ralbovsky NM, Dey P, Galfano A, Dey BK, Lednev IK. Diagnosis of a model of Duchenne muscular dystrophy in blood serum of mdx mice using Raman hyperspectroscopy. Nature Scientific Reports. 2020 Jul 16;10(1):11734. doi: 10.1038/s41598-020-68598-8. About the RNA Institute The RNA Institute at the University At Albany, NY, develops and delivers tools, analytics and early stage discoveries necessary for the progression of RNA-based therapeutics and diagnostics. It brings together leading researchers from higher education and other institutions and industry and offers advanced facilities for RNA research that are critical to new frontiers in human health.

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