Friday 4 June 2010
AVI Biopharma releases promising results from the exon skipping clinical trial
AVI Biopharma has just released promising new results from the ongoing exon skipping clinical trial for Duchenne muscular dystrophy. This trial involves delivering a 'molecular patch' (AVI-4658) to the whole body by intravenous infusion (needle into the vein). This molecular patch is designed to skip exon 51 which could potentially be used to treat 13% of boys with Duchenne muscular dystrophy. The trial's main aim was to assess how safe body-wide treatment with AVI-4658 is and if it is well tolerated by participants.
The 19 participants in the trial were treated with the 'molecular patch' for 12 weeks at six different doses (0.5, 1.0, 2.0, 4.0, 10 or 20 mg/kg). They had muscle biopsies taken before and after treatment and the results of these biopsies have now been press released.
The eight participants who were given the two highest doses showed consistent skipping of exon 51 showing that the drug is active. All of these eight participants also generated new dystrophin protein in the muscle fibres.
Three participants had a strong response with 21%, 15% and more than 50% of the muscle fibres containing dystrophin after treatment with AVI-4658. These three participants were from three different dose groups; 2.0, 10 and 20 mg/kg respectively. This indicates that the response to the treatment was variable from patient to patient. AVI Biopharma commented that they intend to optimise how much of the drug is given and how often to achieve more consistent improvements among patients.
Importantly the 'molecular patch' also appeared to be well tolerated by all participants and no immune response to dystrophin was detected. The trial participants are to be followed up for 14 weeks after their last dose and this is still in progress. The full, detailed analysis of the results of the trial can then be undertaken, including muscle strength and lung and heart function measurements.
Dr Marita Pohlschmidt, Director of Research at the Muscular Dystrophy Campaign said:
These results are exciting and it is encouraging to see this technology bearing positive clinical trial results. The Muscular Dystrophy Campaign has funded research leading to this "Exon Skipping" clinical trial for more than a decade and we are extremely pleased that systemic delivery of the drug leads to a marked difference in dystrophin producing fibers. We are currently funding research to optimise this technology and to make it applicable to more boys with Duchenne.
It will be interesting to understand whether and how the results of the clinical trial translate into improvement of muscle function and we look forward to the publication of the full data and the start of the next phase of the clinical trial.
Prof. Francesco Muntoni, the trial's lead investigator, said:
These results are very encouraging. The muscle cells of the patients at the higher doses had clear qualitative and quantitative changes in their dystrophin expression and this was not associated with any sign of inflammation or immune response against dystrophin-positive fibres. To look at the muscle biopsies of these treated patients under the microscope, and appreciate the new production of dystrophin compared to the pre-treated muscles, reveals a very different picture from that typically observed in patients with Duchenne muscular dystrophy.
This trial demonstrates the potential of a systemically administered drug to induce a substantial new dystrophin protein expression in multiple patients with the condition at levels that may produce a clinically meaningful effect on the course of the disease. Based on these results and on how the patients tolerated the study drug, I believe that AVI-4658 has the potential to become a disease modifying drug in the treatment of Duchenne muscular dystrophy.
Further information and links
To learn more about how exon skipping works please see our FAQ
To read the full press release please visit AVI BioPharma's website.
More information about Duchenne muscular dystrophy.
Read about the Duchenne muscular dystrophy research we fund.
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