Researchers have identified two promising biomarkers for the noninvasive monitoring of Duchenne muscular dystrophy (DMD) disease progression or regression, although more research is necessary. The paper, titled “Comparative mass spectrometric and immunoassay-based proteome analysis in serum of Duchenne muscular dystrophy patients,” was published in Proteomics-Clinical Applications.
Duchenne muscular dystrophy (DMD), one of nine types of muscular dystrophy, is a chromosome X-linked genetic disorder where a mutation leads to the absence of the cytoskeletal protein dystrophin, resulting in progressive muscle weakness and deterioration and cardiac dysfunction — namely, dilated cardiomyopathy. Available therapies include the chronic use of corticosteroids or therapies that aim to restore dystrophin such as translarna, approved in Europe for patients with nonsense mutations. Proper monitoring of disease progression is essential for the development, clinical evaluation, and marketing approval of new potential treatments.
The 6 Minute Walk Test has been used for the conditional marketing authorization of translarna in Europe, although this test is not optimal as it can only be performed by ambulant patients and it does not acknowledge variation of functional ability in different age groups. To overcome such setbacks, molecular markers such as proteins resulting from muscle wasting found in human serum are seen as a promising way to monitor disease progression and treatment response, and also as a diagnostic tool. But detecting such proteins, usually in low abundance in the blood, is a difficult process, and researchers are continuing to try different approaches.
This team aimed to detect a diverse range of protein biomarkers, using techniques such as two-dimensional (2-D) high-performance liquid chromatography (HPLC) protein fractionation followed by identification by LC-MS/MS analysis. Researchers then compared protein profiles between patients of different ages and healthy controls, and between ambulant and non-ambulant patients. Several myofibrillar proteins, likely from muscle fiber breakdown, were found in different profiles in DMD patients and healthy subjects. Furthermore, the analyses applied here confirmed previously reported biomarkers, such as muscle-derived titin, myosin, and carbonic anhydrase I (CA1). The results obtained were further evaluated, and both Gelsolin and CA1 were validated as promising candidates for protein biomarkers.
In the future, researchers want to study other potential candidates, such as fibulin-1 and apolipoprotein B-100. “The combined results of MS- and ELISA-based quantifications indicated more studies are needed to validate this serum protein signature for DMD patients. With these data promising candidate biomarkers have been identified for a rare genetic disease using serum proteome analysis,” the authors concluded.