22 October 2007

A gene therapy clinical trial begins this week which could offer new hope to boys and young men with muscular dystrophy.

A new treatment, called molecular patch therapy, has been developed which has the potential to give boys born with Duchenne muscular dystrophy (DMD) the chance to preserve their muscle function and live into old age.

The antisense oligonucleotide (AO) patches work by masking the faulty part of the gene (exon 51) and allowing shortened but functional proteins to be formed.

DMD affects one in 3,500 boys and is caused by reduced production of dystrophin protein - vital for muscle function. The progression of the condition is so severe that untreated boys lose the ability to walk by their early teens and are only expected to live into their twenties.

Director of Research at the Muscular Dystrophy Campaign, Dr Marita Pohlschmidt, said: “The start of the trial is exciting news because it will provide us with the evidence of how this promising technology will prevent the wasting of muscles in boys with Duchenne muscular dystrophy. In the last 47 years the Muscular Dystrophy Campaign has played a leading role in supporting research into Duchenne by investing over £10m. This is the first time that results from this type of research are so close to being translated into a treatment. We are proud that we were able to play a vital role in the formation of the scientific consortium and to support the preclinical work with more that half a million pounds. Our hopes are high that the outcome of this clinical study will be positive.”

“This is a major breakthrough for the treatment of DMD” said Professor Francesco Muntoni, head of the neuromuscular unit at Imperial College Healthcare NHS Trust. “Conventional gene therapy approach for this disorder has proven to be problematic. Animal work has suggested that the molecular patch has worked well and showed a very significant restoration in dystrophin function."

Professor Muntoni leads the MDEX Consortium, a multidisciplinary enterprise put together by the Muscular Dystrophy Campaign. The consortium promotes translational research into muscular dystrophies. It is formed by the clinical groups of:
  • Professor Francesco Muntoni (Imperial College London)
  • Professor Kate Bushby and Professor Volker Straub (Newcastle University)
  • Professor Dominic Wells and Dr Jennifer Morgan (Imperial College London)
  • Professor George Dickson and Dr Ian Graham (Royal Holloway University of London)
  • Dr Matthew Wood (Oxford University)

The consortium has been responsible for generating and testing multiple molecular patches to find the optimal one to be used in this trial. The molecular patches were tested in cell cultures and the patch that restored the highest level of dystrophin protein is now being taken to clinical trial.

The phase one clinical trial is due to start by the end of October at two of Imperial College Healthcare NHS Trust’s sites - Hammersmith Hospital and at the new Paediatric Research Unit at St Mary’s Hospital.

It will recruit nine young men aged 12-17 with DMD who will have the molecular patch administered by injection into a small muscle in the foot. Subject to the trial’s success, there is already a plan to proceed with another trial to deliver the molecular patch under the skin, so that all muscles in the body could be treated.

The consortium has attracted a large grant from the Department of Health (£1.6 million) which is funding the present study. Recent additional funds from the Medical Research Council (MRC), Muscular Dystrophy Campaign, PPUK, Big Lottery Fund (BLF), Parent Project Muscular Dystrophy (PPMD) and Muscular Dystrophy Ireland (MDI) will allow the consortium to take the current studies forward.