Exon skipping drugs will be used to transform Duchenne muscular dystrophy into a much milder disease as seen in Becker muscular dystrophy patients. eDystrophin is an online database that provides information about inframe mutations typically seen in patients with milder forms of the disease. The database has been constructed using patient records and is easy to use and searchable by mutation type or clinical phenotype.
Correlating dystrophin structure and function with clinical outcomes in Duchenne and Becker Muscular Dystrophy (BMD) patients.
BMD patients display marked differences in their symptoms ranging from asymptomatic to severe disease without a direct link between the size or position of the deletion and the clinical outcome.
Few studies have been published about the specific mutation and severity of the disease in BMD and the introduction of the eDystrophin database attempts to address this. It compliments and extends existing databases of Duchenne human mutations (the Leiden Muscular Dystrophy database and the UMD-DMD French database). eDystrophin is specifically dedicated to providing information about in-frame BMD mutations (deletions, duplications and substitutions) of the DMD gene and the consequences of these alterations from both a clinical perspective and a protein structural perspective.
The eDystrophin database contains 209 different non frame-shifting BMD mutations found in 945 patients. Bioinformatics tools provide models of the three-dimensional protein structure at deletion sites, making it possible to determine whether the mutated protein retains the typical structure of native dystrophin and comparing this with clinical data.
The introduction of the eDystrophin database is timely because of the near-term potential of antisense based exon-skipping drugs to become the new standard of treatment of Duchenne. These therapies aim to transform a Duchenne patient [who expresses no (or very little) dystrophin] into a BMD patient who expresses a mutated but partially functional protein. It will also be useful for other therapeutic opportunities involving gene therapy and micro-dystrophin.
The database is user friendly and informative. It is a source of much needed information for researchers, parents and patients alike. The information it contains will be useful to inform and design therapeutic strategies that lead to treatment and will be updated and expanded with further information from patients as they becomes available.
CureDuchenne is also funding a project to expand the Duchenne database to make it even more relevant and useful for designing treatments and identifying potential outcomes.