MDEX Clinical Trials
MDEX Consortium principal investigators:
Professor Francesco Muntoni (Lead Investigator) Imperial College London
Professor Kate Bushby University of Newcastle
Professor George Dickson Royal Holloway College London
Dr Ian Graham Royal Holloway College London
Professor Dominic Wells Imperial College London
Dr Matthew Wood University of Oxford
Action Duchenne was instrumental in helping to set up the MDEX consortium and went on to lobby for over £2m of government funding for the project to get started. The MDEX project is a clinical trial that will test the possibility of using small molecules called Antisense Oligonucleotides (AO) to skip faults in the dystrophin gene to produce a shorter but functional protein in muscle cells. Exciting recent research relating to a new chemistry for AOs called Morpholinos will mean that the planned clinical trials are being moved forward and should now complete in 2008/9.
Indeed recent research has shown that in animal models these new AOs can be administered systemically (intravenously) and restore the ability to produce dystrophin to levels which approach 70% of the normal levels. This encouraging new animal data suggests that the same AOs which will be given intramuscularly in DMD boys as part of the MDEX trial in the immediate future, could subsequently be given systemically so that a functional benefit for treated boys could be observed. If this therapy works then the severe muscle wasting of DMD should be slowed down and could provide our sons with a longer and improved quality of life. We could have proof of principal in humans that this new exon skipping therapy works by the end of 2008.
Current funding is in place to complete an intra muscular inject trial (IM) by 2007 and the MRC has provided funding for an intravenous (IV) body wide trial that is due to complete by the end of 2008 although the requested funding related to the optimisation of the sequence and the design of experiments aimed at optimising the frequency and dosage of the AO’s administration was cut.
Why do we need further funding for MDEX?
We have to plan for success. Action Duchenne believes that the early pre-clinical trial work on the dystrophic mdx mouse undertaken by the MDEX team had clearly demonstrated the therapeutic potential of their exon skipping strategy. The recent early results from the Dutch trial in humans, while not yet published, equally appears to show therapeutic potential.
The MDEX consortium have now identified AVI Biopharma http://www.avibio.com/ in the USA as suppliers of the Antisense Oligonucleotides needed to develop the clinical trials and also to potentially develop the clinical grade molecules needed for patients in the future.
The MDEX consortium will need substantial further funding to be able take forward the clinical trials to the point of large scale production.
It is vital that, if the trials yield promising results, there can be access to further funding in the near future rather than having to wait for specific funding announcements from the DoH, Research Councils and other funding bodies. The current system of funding introduces too many delays that seriously impact on the pace of development of trials. Action Duchenne recognises that such funds will only be made available on the basis of positive results but wish to stress that the process of applying for further funding should be simplified and made available in response to positive results.
As the MDEX project has progressed it has become increasingly clear that more resources are needed for project management, submission of clinical protocols and legal agreements and contracts to be drawn up for partnerships with bio tech companies like AVI.
Action Duchenne is calling for a detailed review of the funding requirements to be made for the MDEX project and delivery of a treatment to patients. However Action Duchenne has received advice that approximately £280,000 is needed immediately to facilitate the project management and legal resources necessary to help MDEX move forward from it’s present position. Additionally Action Duchenne has received advice that approximately £15m will be required to be ring fenced by the Government and the DoH over the next 5 years in order to be able to take any successful molecule through to patient delivery.
We believe that these measures will enable the MDEX project to deliver the first gene therapy for our generation of boys with Duchenne Muscular Dystrophy.