#apaperaday: Muscle histological changes in a large cohort of patients affected with Becker muscular dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Muscle histological changes in a large cohort of patients affected with Becker muscular dystrophy.

Today’s pick for today is by Ripolone et al in Acta Neuropathologica Communications on muscle histology in Becker patients. Doi 10.1186/s40478-022-01354-3

Becker muscular dystrophy is caused by mutations allowing production of partially functional dystrophins. These do not fully prevent muscle fiber damage during contraction. Becker patients have inflammation, necrosis, de- & regeneration & replacement of muscle by fibrosis & fat.

The disease is very variable in age of onset and progression which makes clinical trial design challenging. Here authors share results of analysis of biopsies of 45 Becker patients who are recruited into the Italfarmaco Givinostat clinical trial.

Becker patients were 19-62 years old and symptoms started between age 2 and 40 years. Cross sections were made of 45 Becker and 15 control biceps muscle biopsies and stained and analyzed by blinded operators (very good!)

Compared to the healthy biopsies Becker biopsies showed more variability in fiber size (while the mean size did not change). The muscle fiber area was reduced in Becker, while there was more fibrosis and more centrally located nuclei. Fat was observed in biopsies from 9 patients.

There were more fibers expressing embryonic myosin heavy chain (regeneration sign) in Becker biopsies. Authors divided patients in mild, moderate & severe groups based on histology. Patients expressed 10-78% dystrophin. Levels did not correlate with histology or function.

There was a correlation between muscle fiber area & functional outcomes. Authors performed principal component analysis (which parameters contribute most to an outcome?) showing fat, fibrosis & low muscle fiber area contributed to worse function.

Very nice work. Authors discuss that because these were patients fulfilling inclusion criteria for a trial their cohort is limited. However I applaud the authors for sharing the baseline data. Looking forward to more data of the trial.

 

Pictures by Annemieke, used with permission.