Prof. Annemieke Aartsma-Rus is taking on a challenge by reading and commenting on a paper a day. She shares her insights, findings and thoughts via her @oligogirl Twitter account. See below the overview of April 2022.
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.
Prof. Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics at the Department of Human Genetics of the Leiden University Medical Center. Since 2013 she has a visiting professorship at the Institute of Genetic Medicine of Newcastle University (UK).
Her work currently focuses on developing antisense-mediated exon skipping as a therapy for Duchenne muscular dystrophy. In addition, in collaborative efforts she aims to bridge the gap between different stakeholders (patients, academics, regulators and industry) involved in drug development for rare diseases.
In 2013 she was elected a member of the junior section of the Dutch Royal Academy of Sciences (KNAW), which consists of what are considered the top 50 scientists in the Netherlands under 45. From 2015 to 2022, she was selected as the most influential scientist in Duchenne muscular dystrophy by Expertscape.