Welcome to the MDEX Consortium

SAB-MDEX Consortium: The next joint meeting of SAB-MDEX Consortium will be held on Wednesday 05th March 2014 in London to follow the MRC meeting earlier in the week.

MDC Award

Every year the Muscular Dystrophy Campaign’s President’s Awards are held at the national conference, this year in Nottingham. The President’s Awards are an opportunity for the charity to give thanks to all those who have made a significant difference to people living with neuromuscular conditions; fundraisers, campaigners, health professionals and scientists alike.

In 2013, Professor Francesco Muntoni and the members of the MDEX Consortium have been chosen for the “Scientists of the Year” award for leading ground breaking work in the development of exon skipping technology and moving it forward into clinical trials. The award was presented on 12th October 2013.

UPCOMING SYSTEMIC ANTISENSE OLIGONUCLEOTIDE (AON) TRIALS IN DMD

Two studies are planned to start in 2013 using the 2’OMe chemistry developed by Prosensa (www.prosensa.eu). Both studies will be sponsored by Prosensa and in two sites in the UK (London UCL/GOSH and Newcastle).

The first study, will have a DMD genotype skippable for exon 45 with the deletions of exons 44; 46-47; 46-48; 46-49; 46-51; 46-53; 46-55. DMD boys need to be ambulant and able to comply with study procedures and approximately 10 boys will be recruited.

The second study will have a DMD genotype skippable for exon 53 with deletions of exons 42-52; 45-52; 47-52; 48-52; 49-52; 50-52; 52. This study will recruit approximately 5 ambulant boys. Further information is available on www.prosensa.eu/duchenne-muscular-dystrophy/faq

A number of eligible DMD boys are already known to the two recruiting sites. Recruitment has started for both studies and families are being approached. However, other UK centres are encouraged to contact either Hinal Patel, Clinical Trials Coodinator ( hinal.patel@ucl.ac.uk ) or Becky Davis, Clinical Trial Coordinator (  becky.davis@newcastle.ac.uk  ).

SKIP-NMD (www.skip-nmd.eu): A team of scientists from several European countries and the USA, led by UCL scientist Prof. Francesco Muntoni, Dubowitz Neuromuscular Centre, Institute of Child Health has won an EU Health Innovation-1 2012 Collaborative research grant, 305370, to perform a clinical trial to test a novel drug treatment in Duchenne muscular dystrophy (DMD) boys. The total award is ~€5.5 million, with a ~€1.44 million budget allocated to UCL and Great Ormond Street Hospital (GOSH). The work would not be possible without the involvement of Sarepta Therapeutics, Cambridge, MA, USA) who are not only providing the drug, but also half of the drug production and pre-clinical and clinical trial costs. (see under News for full press release).

The MDEX Consortium was formed to develop and test treatments for Duchenne muscular dystrophy. In the last few years the MDEX Consortium has focussed on a strategy of using patches of genetic material (Antisense Oligonucleotides) to restore production of the essential muscle protein dystrophin.The activities of the MDEX Consortium are divided into several sections, each led by a different research group (see profiles) but with all members of the Consortium sharing results and meeting regularly. The project also benefits from regular input from a Scientific Advisory Board of experts (see Scientific Advisory Board).

(PIs and Postdocs at the MDEX Consortium meeting 03.11.11 at UCL/ICH)

Originally the work of the MDEX Consortium was funded by the Department of Health (UK) in 2005. This project was focused on the search of the most effective molecular patch to promote the restoration of dystrophin production in Duchenne boys carrying specific genetic changes (deletions). This culminated in a phase lb/lla clinical trial in a group of boys who received the molecular patch AVI-4658 intramuscularly (Kinali et al, Lancet Neurology 2009). A summary of the outcome can be seen under latest news on this website. This was followed by funding from the MRC UK and the sponsor AVI Biopharma for a dose escalation systemic trial in 19 patients at the Great Ormond Street Hospital (GOSH), London and the Newcastle Royal Infirmary. The data was published in the high impact journal Lancet in 2011.

Link to Lancet paper:http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60756-3/fulltext.View the full press release in our News section.

Additional insight into this study can be viewed in the MRC highligtshttp://www.mrc.ac.uk/About/AnnualReview09-10/SevenAges/Childhood/Hopeformuscular/index.htm

The UK North Star Clinical network, which links over 20 UK centres involved in the diagnosis and management of DMD (www.northstardmd.com or www.muscular-dystrophy.org/how_we_help_you/for_professionals/clinical_databases)   were closely associated in the above studies and made referral of patients. Q&A relating to exon skipping can be viewed in this website and the Clinical Trials website http://clinicaltrials.gov/ct2/show/NCT00844597.

The United States Adapted Names Council approved the nonproprietary name ETEPLIRSEN for AVI-4658.On 12 Jul 2012 AVI BioPharma announces corporate name change to Sarepta Therapeutics. 

Funding Awards: In addition to the above funding, the MDEX Consortium has been succesful in obtaing awards from (1) from the Department of Health and the Wellcome Trust for a period of 36 months totalling up to nearly Ł2.5 Million for the study ‘Advanced antisense oligonucleotide technology for exon skipping in Duchenne muscular dystropy’ and (2) from Association Francaise contre des Myopathies (AFM) for a period of 48 months totalling upto €3.9 Million for the study ‘Advances in oligonucleotide-mediated exon skipping for DMD and related disorders’. Both awards were to Professors Matthew Wood and Francesco Muntoni. The awards will facilitate research in the laboratories of Professor Matthew Wood (Oxford), Professor Francesco Muntoni/Dr Jenny Morgan/Dr Steve Hart (UCL/ICH), Professors Kate Bushby/Volker Straub (Newcastle), Professor George Dickson (Royal Holloway), Professor Dominic Wells (Royal Veterinary), Dr Mike Gait (Cambridge), Professor Bernard Lebleu (Montpellier) and Professor Thomas Voit (Paris).

GSK/Prosensa clinical trial in DMD boys with study drug GSK2402968 (PRO051/Drisapersen): A multicentre trial with this study drug recruited DMD boys in UK at the Great Ormond Street Hospital(GOSH), London and at the Royal Victoria Infirmary (RVI), Newcastle. It is a Phase lla, double blind, exploratory, parallel clinical trial to assess the optimal dose of GSK2402968 for safety, tolerability and efficacy, in ambulant patients with DMD. A total of 10 DMD boys were recruited in the UK, 5 at the RVI and 5 at GOSH. Five boys from GOSH and four from Newcastle have now enrolled into the extension study after completing their initial treatment. However, dosing of the study drug has been stopped for data analysis. GSK/Prosensa has released its latest data on the study drug (phase lll) and this can be viewed on the following link