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 March 2022.
Prof. Aartsma-Rus reads and comments on the paper titled: Growth pattern trajectories in boys with Duchenne muscular dystrophy
Today’s pick is from Orphanet Journal of Rare Diseases by Stimpson et al on the influence of corticosteroids regimen on growth pattern trajectories in Duchenne patients using the NorthStar UK database retrospectively. Doi 10.1186/s13023-021-02158-9
Duchenne is caused by lack of dystrophin. All Duchenne patients miss full-length dystrophin (Dp427), expressed in muscle, heart & brain. Some patients also lack shorter dystrophins such as Dp140 (mainly expressed in the brain). Rarely patients also lack Dp71 (expressed everywhere).
Some dystrophin restoring treatments are approved for subsets of patients in specific regions. However, for most patients the only treatment is ‘standards of care’, which includes the use of glucocorticosteroids such as prednisone and deflazacort.
Steroid use slows down disease progression significantly but also causes side effects such as weight gain and growth stunting (amongst many others). Different regimens are known, daily and intermittent (often 10 days on and 10 days off – aimed at reduction of side effects).
Authors here retrospectively look into the NorthStar UK database to study the growth patterns (weight, height and BMI) for Duchenne patients for different steroid regimes. 598 patients were included with a combined 2604 observations over on average 2.5 years.
They compared different steroid groups: no steroid (10%), prednisone (62%, with 34% daily and 29% intermittent), deflazacort (28%, with 20% daily and 8% intermittent). At 5 years of age patients using deflazacort were heavier than naïve or prednisone treated patients.
However, the weight gain over time was higher for the prednisone treated patients. Authors discuss that there might have been a bias where clinicians prescribe deflazacort primarily for patients who are heavier knowing that this is associated with less weight gain.
In other words the deflazacort use at 5 years might be due to weight rather than be caused by it. The height at 5 years was the same for all groups, over time there was growth stunting seen for all patients on daily regimen. Note that even naive patients were shorter than peers.
Growth stunting was most apparent for daily deflazacort. Authors also looked whether growth patterns differed based on loss of only full-length dystrophin or also other dystrophins. They observed that patients missing all dystrophins (also Dp71) were shorter.
No difference between patients lacking only full-length or also Dp140. There were no differences between different exon skippable groups (exon 8, 44, 45, 51 & 53 skipping). In this cohort weight appeared not to influence loss of ambulation, while height did in 10-11 year olds.
Authors discuss the limitations of their study, which is retrospective so there is the usual issue of missing data points. Furthermore, the deflazacort group is small as this steroid has only recently started to be prescribed by UK clinicians.
Authors stress that they did not include the doses in their analysis, while this likely has influenced results. Authors speculate that the smaller height of patients missing all dystrophins (also Dp71) may be because this protein is involved in endocrine regulation of growth.
However, I would add that given that this group is very small, it is also possible that this is a chance finding. Agree with the authors that more study is needed. As discussed earlier in a study about Duchenne and BMI measuring height is challenging in older Duchenne patients.
In conclusion, authors see more weight gain for prednisone and more height stunting for deflazacort in their UK cohort. Looking forward to the FOR-DMD study where different regimens were compared as well but then prospectively and using standardized doses.
This mouse doctor thinks that based on results she has seen so far it is clear that steroid treatment is better than no steroid treatment for Duchenne, but that prednisone and deflazacort do not seem to vary much for efficacy and side effects. Let’s see what FOR-DMD data says.
Pictures by Annemieke, used with permission.
About Professor Annemieke Aartsma-Rus
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.