The main goal of the FP7 funded SCOPE-DMD project is to further advance and accelerate the development of PRO045, an exon-skipping compound for DMD. PRO045 is currently in a Phase IIb dose-escalating clinical trial to assess its safety and efficacy. The chemically-modified AON induces exon 45 skipping in the dystrophin gene and could be suitable for approximately 8% of all DMD patients.
When deletions are present in the DMD gene, these result in an out-of-frame dystrophin transcript and therefore, a truncated and non-functional dystrophin.
AONs are short nucleotide chains that can bind to a selected complementary nucleotide sequence of the (pre-)mRNA and can induce exon skipping mechanism by blocking splicing enhancer sequences present in the exon, leading to a lack of exon recognition by the RNA splicing mechanism (see figure b, where the AON named PRO045 binds sequences in exon 45).
This results in the restoration of the open reading frame of the dystrophin mRNA such that an internally truncated but semi-functional dystrophin protein (Becker-like dystrophin or BMD-like protein) is expressed in the muscles. Based on BMD clinical experience with typically improved prognosis, it is expected that AON treated patients will have improved muscle function due to expression of this BMD-like dystrophin. This RNA-based approach is not gene therapy, but rather genetic therapy or RNA modulation, as it does not change the DNA code. The effects of AON therapy on the pre-mRNA can be halted by stopping the systemic administration of the compound.
Partner 1 – UNEW – University of Newcastle, UK – http://www.treat-nmd.eu/
Partner 2 – BioSpring – BioSpring Gesellschaft Fur Biotechnologie MBH, Germany – http://www.biospring.de/
Partner 3 – IOM – Association Institut de Myologie, France – http://www.institut-myologie.org/
Partner 4 – BioMarin – BioMarin Therapeutics – http://biomarin.com
Partner 5 – LUMC – Academisch Ziekenhuis Leiden – Leids Universitair Medisch Centrum, Netherlands – https://www.lumc.nl/
DMD is an inheritable, X-chromosome linked, lethal childhood disease with a prevalence between 0.32 and 0.52 per 10,000 inhabitants. Worldwide, around 240,000 boys suffer from DMD. DMD is caused by mutations (often deletions) in the dystrophin gene that result in the disruption of the open reading frame leading to a loss of dystrophin protein expression.
Should you have any questions regarding BioMarin trials, or Duchenne Muscular Dystrophy please contact:
Paul Humphrey – Associate Director Patient Advocacy for the EU region: Paul Humphrey
Please also visit the BioMarin website for further details: http://biomarin.com
The following website also has excellent information on DMD, current research and trials: http://www.treat-nmd.eu/
SCOPE – DMD partners met up twice a year to discuss project progress.
These meetings were held on the following dates:
- 28th January 2014 London
- 16th and 17th July 2014 Paris
- 21st and 22nd January 2015 Leiden
- 1st and 2nd July 2015 Newcastle
- 28th January 2016 Leiden
Our Final Project Meeting was held on the 25th and 26th May 2016 London
Stakeholder meeting one – 2015
Videos of SCOPE-DMD/COST stakeholder meeting 29 April 2015
This meeting was jointly organized by SCOPE-DMD and COST Action BM1207 – Exonskipping.eu – the meeting was hosted by the EMA in London. To watch a specific video hover over the bottom of the video and select the playlist icon to see everything that is available.
Alternatively you can access the videos by going directly to YouTube.
Stakeholder meeting two – 2016
This project received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 601573