#apaperaday: Functional outcome measures in young, steroid-naïve boys with Duchenne muscular dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Functional outcome measures in young, steroid-naïve boys with Duchenne muscular dystrophy.

Today’s pick is from World Muscle Society journal Neuromuscular Disorders about functional outcomes in steroid naive patients from baseline data in FOR-DMD study by Mayhew et al doi 10.1016/j.nmd.2022.02.012.

Duchenne is a severe progressive disease. There is no cure, but multidisciplinary care can slow down disease progression. Part of the care (as recommended by guidelines) is the use of glucocordicosteroids. Usually the treatment is initiated between age 4 and 7.

Limited data is available for steroid naïve children in this age range. Here authors share the baseline data of patients involved in the FOR-DMD trial (that compares daily vs intermittent prednisone vs daily deflazacort)

Baseline data was available for 196 patients who were evaluated with multiple functional analyses. It is clear that scores generally improve with age until ~6  This is because patients mature and grow. For respiratory function (FVC) this continues until age 7.

Authors also compared patients for whom both baseline and screening data were available – the same functional tests done up to 90 days apart. Generally there was very good test-retest reliability except for the 6 minute walk test in patients <5 years.

Authors stress in the discussion that age alone is not a predictor of severity. On average functional scales may improve but when decline starts varies per patient. Kudos to the authors for sharing the data and performing these analyses.

After 18 months cas9 was still expressed in the edited mouse. While this resulted in cumulation of edited nuclei from a safety perspective the long expression of cas9 is worrying. Authors checked for predicted off target cuts and did not detect those.

But there might have been an unpredicted off target effect and in human expression will be longer than 18 months (one expects) so there will also be more time for them to accumulate.