The TREAT-NMD global Duchenne muscular dystrophy (DMD) patient registry

Zaïda Koeks, Netherlands

1st year PhD student and 3rd year neurologist in training Leiden University Medical Center (LUMC), The Netherlands

From the 21st of October until the 2nd of November I worked on a short term scientific mission (STSM) at the TREAT-NMD office at the Institute of Genetic Medicine, Newcastle UK, using COST funding.

TREAT-NMD recently succeeded in the collection of an unique set of data derived from 32 national Duchenne muscular dystrophy (DMD) patient registries worldwide. The ultimate goal is to create a centralised worldwide global DMD patient registry. The information collected follows a mandatory and/or highly encouraged set of questions agreed on by the TREAT-NMD global database oversight committee.

The aim of my two week STSM was to collaborate with Dr Catherine Bladen (senior research associate and manager of the global DMD database) on the creation of the global DMD patient registry and to contribute to the analysis of the collected data. It is expected that, after completion, this registry will lead to major findings and insights in disease specific milestones and care for DMD patients around the world. After detailed analysis of genetic data the registry will also yield information on mutations and clinical characteristics of the cohorts of DMD patients eligible for different exon skipping therapies. Recruitment of patients for future clinical trials, including trials for exon skipping therapy, will also be facilitated.

First we reviewed all 32 national registries focusing on the amount and quality of data collected. Not all countries were able to collect all mandatory and/or highly encouraged items. Most centres used the TREAT-NMD recommended HGVS nomenclature but some variability was noted in annotation of the different mutations between countries. Harmonisation of all genetic data appeared to be too time consuming for this two week project. We decided to solve this problem at a later time in collaboration with the involved bioinformatics software engineer in Marseille, France.

Hereafter we focused on the demographic data. Up to now the registry contains 6787 DNA confirmed DMD patients. It is expected that this number will increase to up to 9000-10.000 patients after harmonisation of genetic data. Included national registries are from Argentina, Australia, Belgium, Bulgaria, Canada, China(2), Croatia, Egypt, Estonia, Finland, France, Germany, Greece, Hong Kong, India, Iran, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Romania, Russia, Serbia, Spain, Switzerland, Turkey, the United Kingdom, Ukraine and the United States. Most patients in the registry are between 6 to 14 years old. Use of corticosteroids, as recommended by the clinical standards of care recommendations, is still variable between different age groups and countries. We analysed the influence of corticosteroids on ambulation, scoliosis and cardiomyopathy. As expected, our findings show that corticosteroids appear to have a significant positive effect on ambulation and scoliosis but not (yet) on cardiomyopathy. These results were presented on the 30th of October during the TREAT-NMD conference at the end of my STSM.

In conclusion, we succeeded in the collection of the raw data from 32 national databases. This has led to a large global DMD patient registry and important demographic data. Additional analysis and correlations will be performed in the near future. Thanks to this STSM I am now able to continue my collaboration with the manager of the global DMD database at the TREAT-NMD office, contributing to the creation of the global DMD patient registry and analysis of collected clinical and genetic data.

October 2013