Latest Drug Trial Shows Potential RNA Therapeutic Treatment For Duchenne Muscular Dystrophy, Says Action Duchenne

Main Category: Muscular Dystrophy / ALS
Article Date: 22 Jan 2009 - 3:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

Leading RNA-based biopharmaceutical company announces successful clinical trials for treatment of muscle wasting disease by 'exon skipping'

Action Duchenne states that the latest results of a study released by AVI BioPharma Inc, a developer of RNA-based drugs, demonstrate that Duchenne Muscular Dystrophy could be treated successfully by exon skipping. The clinical trial of the drug AVI-4658, developed by AVI BioPharma, was funded by the Department of Health (UK) and conducted by the members of the MDEX* consortium, led by Professor Muntoni at UCL Institute of Child Health London. Biopsy data showed that injection of the drug into the foot muscles of a series of Duchenne patients successfully induced new dystrophin production. The study data will also be published in a specialist medical journal.

Recruitment of Duchenne patients for a further AVI-sponsored trial to see if this drug can be delivered body wide is now underway. The MDEX team will be using Action Duchenne's DMD Registry www.dmdregistry.org to help in recruiting Duchenne boys with specific gene variations for this new clinical trial. The trial, which was opened in December 2008, will administer AVI-4658 systemically to see if dystrophin can be produced in all muscles. It is hoped that this might slow the very severe progression of the disease.

Duchenne Muscular Dystrophy affects 1 in 3,500 male births in the UK, and is the most common and severe type of muscular dystrophy - sufferers are diagnosed usually by the age of 5. Patients with DMD and Becker Muscular Dystrophy (BMD) are boys and young men who lack dystrophin, a protein that is critical to the structural stability of muscle fibres. Patients develop progressive muscle weakness. Duchenne affects all muscles including the heart and respiratory system leaving young people paralysed by late teens and many patients do not live past their twenties.

Recent research by the MDEX Consortium has demonstrated that short molecules - called antisense oligonucleotides (AOs) - can restore the production of dystrophin protein to affected tissues. This is done by a process called 'exon skipping', in which the parts of the genetic code affected by a mutation are "patched" by AO's so that that the code can be correctly read.

This latest drug AVI - 4658 is designed to skip exon 51 of the dystrophin gene, allowing for restoration of the reading frame in the mRNA sequence. Restoration of dystrophin production achieved by skipping this exon may potentially improve or significantly slow the disease process, thus prolonging and improving the quality of life for the affected patient.

Nick Catlin, CEO of Action Duchenne said, "These early results that show exon skipping therapy can be a potential treatment for Duchenne Muscular Dystrophy is promising news that will be welcomed by all sufferers and their families. The MDEX Consortium has made some tremendous progress in researching treatments for this disease and this latest great work underlines the value of continuing to actively raise funds to support this important cause."

About AVI BioPharma

AVI BioPharma is focused on the discovery and development of RNA-based drugs utilizing proprietary derivatives of its antisense chemistry (morpholino-modified phosphorodiamidate oligomers or PMOs) that can be applied to a wide range of diseases and genetic disorders through several distinct mechanisms of action. Unlike other RNA therapeutic approaches, AVI's antisense technology has been used to directly target both messenger RNA (mRNA) and its precursor (pre-mRNA), allowing for both up- and down-regulation of targeted genes and proteins. AVI's RNA-based drug programs are being evaluated for the treatment of Duchenne muscular dystrophy as well as for the treatment of cardiovascular restenosis through our partner Global Therapeutics, a Cook Group Company. AVI's antiviral programs have demonstrated promising outcomes in Ebola Zaire and Marburg Musoke virus infections and may prove applicable to other viral targets such as HCV or Dengue viruses.

For more information, visit http://www.avibio.com.

*About the MDEX Consortium

The MDEX consortium led by Professor Muntoni, is a mutlidisciplinary enterprise to promote translational research into muscular dystrophies, and is formed by the clinical groups of Professor Francesco Muntoni (Imperial College London and UCL Institute of Child Health) and Professor Kate Bushby and Professor Volker Straub (Newcastle University), and scientists from Imperial College London (Professor Dominic Wells), UCL Institute of Child Health (Dr Jennifer Morgan), Royal Holloway University of London (Professor George Dickson and Dr Ian Graham), Oxford University (Dr Matthew Wood) and University of Western Australia (Prof Steve Wilton). In addition, the charities Muscular Dystrophy Campaign (MDC), Action Duchenne and Duchenne Family Support Group also participate in the Consortium.

For more information visit http://www.mdex.org.uk

About Action Duchenne

Action Duchenne (formally Parent Project UK) was set up by Duchenne families in 2001 to promote new research for a cure for Duchenne. The charity has a strong record in funding research and has to date funded 8 major projects costing over £1m and has lead the £1.6m DoH funding of the MDEX project. These projects have enabled much needed early work to be completed on exon skipping and other therapeutic approaches. Action Duchenne holds an international conference every year to bring together researchers and families to exchange new research developments and provide a vital meeting venue for scientists.

In 2005 Action Duchenne launched the Duchenne Patient Registry, the first National Duchenne database that holds gene information of people living with Duchenne and can be used to speed up the recruitment of patients for clinical trials. http://www.dmdregistry.org

In 2006 Action Duchenne launched a comprehensive learning and behaviour toolkit for use by parents and education professionals.

Action Duchenne