A molecule detectable in urine could become a novel biomarker for Duchenne muscular dystrophy (DMD), according to a study recently published in Neuromuscular Disorders.
“Here, we demonstrated that the elevated titin in urine is directly associated with the lack of dystrophin and urine titin responses to drug treatment,” the authors wrote.
This experimental study included C57BL/10-mdx/Jcl (mdx) and C57BL10SnSlc (WT) male mice. The mdx mice had a mutation in the DMD gene, specifically, exon 23, which generates a termination of functional transcripts, yielding a mice model without dystrophin, the protein absent in DMD. The WT mice served as the control group.
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The researchers collected urine samples from both groups and compared them to analyze and identify differences in their composition, specifically, titin levels. Mice that lacked dystrophin showcased a decreased amount of titin in the urine compared to the controls.
Moreover, after the DMD mice received treatment with an exon skipper that aimed for exon 23 of the DMD gene and subsequently elevated dystrophin levels, the urine levels of titin markedly decreased.
These findings suggest a direct relationship between the presence of functional dystrophin protein and the levels of titin in urine. Importantly, the researchers also analyzed urine samples from patients with DMD, detecting a similar pattern with a higher titin concentration, further implying the possibility that these results could extrapolate to humans.
A novel biomarker for DMD that could aid in its diagnosis, disease progression, and treatment response would represent an important advance for patients with this genetic abnormality.
Currently, muscular creatinine kinase (CK-M) serves as a marker for this disease. However, it faces many challenges; for example, its levels can be measured in blood samples, making it an invasive procedure. Also, this marker lacks specificity, as many other entities also increase blood levels of CK-M.
“Furthermore, blood volume and frequency of blood collection are limited in the pediatric population,” the authors noted.
Titin is the largest protein in human physiology. It is also called connectin and aids in striated muscle contraction and relaxation.
Niki M, Nakashima M, Kamiguchi H, et al. Urine titin as a novel biomarker for Duchenne muscular dystrophy. Neuromuscul Disord. Published online February 13, 2023. doi:10.1016/j.nmd.2023.02.003