#apaperaday: Longitudinal assessment of blood-borne musculoskeletal disease biomarkers in the DE50-MD dog model of Duchenne muscular dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Longitudinal assessment of blood-borne musculoskeletal disease biomarkers in the DE50-MD dog model of Duchenne muscular dystrophy.

Paper is a preprint from Wellcome open research by Riddell et al on serum biomarker levels in a Duchenne dog model. Longitudinal study in 18 affected and 14 control dogs. Doi 10.12688/wellcomeopenres.17398.1.

The dog model is the DE50-MD model with a splice site mutation causing exon 50 skipping & lack of dystrophin. Blood was taken monthly from wild type & affected dogs. CK was elevated as expected, even in days old pups (like patients).

CK is a marker for muscle damage. It is prone to variation due to e.g. exercise. Myomesin 3 is another marker for muscle damage that is less variable. It has been shown elevated in Duchenne patients and mdx mice and also was elevated in the DE50-MD dogs.

Myostatin is expressed lower in Duchenne patients & DE50-MD dogs. Mi-RNAs specific for muscle (myomirs miR 1, 133a & 206) are elevated in both. Authors calculated that due to large differences between healthy & DE50-MD dogs small groups would suffice to detect biomarker effects.

Biomarker response depends on the mechanism of action of the treatment. These biomarkers are all markers of muscle damage & quality. If the integrity of fibers improves, biomarkers would change. But if fibrosis would increase, levels would change similarly: cannot use them in isolation.

I like that the authors used longitudinal samples and hope more (beyond 18 months) will come with time. I also look forward to studies where authors assess the effect of treatments on these biomarkers. And kudos for sharing early!