Monday 11 May 2009
Exclusive visit to Professor Dame Kay Davies' lab
We visited Professor Dame Kay Davies' laboratory at the University of Oxford for a behind the scenes look at their ground breaking research. We were joined on this visit by several supporters including trusts and foundations who were so impressed by the research that financial support has been pledged which will allow the research to continue for a further three years.
Prof. Davies started the afternoon with an overview of the lab's recent progress in developing therapies for Duchenne muscular dystrophy. The funding strategy for her work was also discussed, with charity and government funding and industry partnerships all being key to successfully developing a treatment. A more in-depth account of the research was then given by two post-doctoral researchers from Prof. Davies' laboratory.
Contents:
Searching for drugs to increase 'utrophin'
Dr Rebecca Fairclough presented the latest results of her work on the protein 'utrophin' which is funded by the Muscular Dystrophy Campaign. It is thought that utrophin may be able to compensate for the lack of dystrophin in boys with Duchenne muscular dystrophy since both proteins are structurally similar and appear to have very similar functions. Increasing levels of utrophin could potentially be a treatment which would be applicable to all boys with Duchenne muscular dystrophy, regardless of their type of mutation.
Many years of studying utrophin and how its production is controlled, has enabled the researchers to now begin to develop drugs which may increase levels of utrophin protein in the body. One drug is already being taken forward by the Oxford biotechnology company Summit plc in collaboration with BioMarin, a US pharmaceutical company.
Dr Fairclough is continuing the search for more drug candidates to increase the chances of finding a drug that is effective and safe in humans. To help in their search they are developing a new mouse model. Mice which lack dystrophin are being genetically engineered to emit light when the gene for utrophin is switched on. The amount of light produced will tell the researchers how efficient their drugs are at switching on the utrophin gene. This is achieved by inserting a light producing gene from the firefly into the mice. This new mouse model will make it quick, easy and non-invasive to determine which drugs are working.
Developments in exon skipping
Dr Aurelie Goyenvalle then presented her exciting new work on exon skipping. This involves short strands of DNA, known as 'antisense oligonucleotides' (AOs), or 'molecular patches' which can restore the production of the protein dystrophin.
Exon skipping works by masking the faulty part of the dystrophin gene, allowing a shortened but functional dystrophin protein to be produced.
A major challenge of exon skipping is to deliver the 'molecular patches' to all of the muscles of the body in high enough quantities to make a significant difference to the function of the muscles. Dr Goyenvalle is investigating the use of viruses to deliver the 'molecular patches' into the muscle cells of mice with promising results so far.
Laboratory tour and interview with Prof. Davies
After the presentations we toured of the laboratory, which gave us the opportunity to look down microscopes at muscle cells and examine the state of the art equipment being used by the research team. During our tour we had the opportunity to ask Prof. Davies a few questions:
Q. How did you get involved in doing research in the field of Duchenne muscular dystrophy?
I originally came back to London to work in on cystic fibrosis. We wanted to develop a prenatal diagnostic test but didn't know what chromosome the cystic fibrosis gene was on. So we used Duchenne muscular dystrophy as a model disease first, because we knew the chromosome that was on; the X chromosome as it only affected boys.
Then I met my first patient and got involved with the Muscular Dystrophy Campaign and haven't looked back since.
Q. Is there a particular aspect of work that you enjoy most?
I enjoy all of it. Actually each day is different. Sometimes you have set backs and things happen that are unexpected but take you forward. It's always exciting.
Q. What is the aim of your current work?
The aim is to use the new mouse model that we've developed to find more drugs to upregulate utrophin to try to treat Duchenne muscular dystrophy. We've just got the mice now and so we're setting up new screens. We've got one compound that's being taken care of by the biotechnology company BioMarin that was passed on from Summit. So now our job is to find new compounds.
