VASTox announces positive DMD preclinical news
results in its drug discovery programme, which aims to find the
next generation of treatment for Duchenne Muscular Dystrophy (DMD),
a disease of which there is no known cure.
Providing a truly effective treatment has proved difficult, as is the case with nearly all congenital disorders. DMD is caused by the absence of the protein dystrophin. The disorder occurs in about 1 in 3,000 males, with around 30 per cent of DMD cases arising in boys with no family history of the disease.
The lack of the protein dystrophin results in severe skeletal and heart muscle deterioration. The disorder is progressive and it is rare for a male to survive beyond the age of 25.
Preclinical studies revealed that in vivo up-regulation (increased production) of the protein utrophin was made possible by a number of small molecules from its proprietary chemical library.
This is a significant development as utrophin has been demonstrated to replace the function of dystrophin, which is missing in DMD patients and helps keep muscle cells intact.
"I am delighted to see, for the first time, in vivo up-regulation of utrophin using small drug-like molecules. I believe that up-regulation of utrophin currently offers the most promising avenue for the development of a new treatment for Duchenne Muscular Dystrophy," said Kay Davies, Dr Lee's professor of anatomy and director of the MRC Functional Genetics Unit, University of Oxford, and co-founder of VASTox.
VASTox intends to optimise and develop the most promising lead candidates from this on-going study, and conduct a more extensive screen for additional compounds in 2006 with the aim of selecting a clinical candidate in 2007.
The compounds that have demonstrated the ability to up-regulate utrophin have also undergone a preliminary toxicology assessment using its zebrafish assays.
This approach allows the company to eliminate potentially toxic compounds much earlier in the development process than normal, reducing cost and time of early drug discovery.
"We are pleased that we have validated our zebrafish genomics platform to screen out potentially toxic small molecules, thereby cutting-down on the need for higher animal testing," said Steven Lee, CEO of VASTox.
Using zebrafish and fruitflies for genomic studies can decrease time and cost of drug discovery and development. This is because using whole organisms allows it to carry out high volume, high content screening that delivers data, which is predictive of the efficacy and toxicity of potential drug compounds in humans.
Research into Duchenne Muscular Dystrophy has never given sufferers a better chance of finding a cure or at the very least an improved treatment. Improved techniques in sequencing and testing have allowed scientists to get to the very heart of the disorder at a genomic level.
2005 saw the ongoing development of a drug that causes cells to "read through" genetic errors, thought to affect some 15 per cent of children with Duchenne muscular dystrophy. Its developer, PTC Therapeutics, receives a $1.5 million (€1.2 million) grant to continue testing PTC124 in boys with DMD.
Likewise, gene therapy researchers associated with the biotechnology company Asklepios and several universities received a green light from the Recombinant DNA Advisory Committee of the National Institutes of Health to move forward toward human testing of a gene therapy compound for Duchenne muscular dystrophy.
The UK MDEX group recently announced a clinical trial programme that could see systemic delivery of Antisense Oligonucleotides that are able to fix the gene and hopefully produce a Becker MD as opposed to the much more severe Duchenne form of the disease.
The programme has been bought forward so that both intra muscular and intravenous trials should complete by early 2008. This should give us a clear indication of the possible therapeutic benefits of exon skipping. The Dutch group from Leiden are also developing parallel trials.
