Researchers at the Laval University Hospital Center in Quebec are developing an approach that might expand the type of disease treatable with gene therapy. Most gene therapy treatments are being developed to insert a functional version of a gene into patients with a defective one, usually from a congenital abnormality. However, the group at Laval University Hospital is working to develop an approach to correct diseases where, instead of a defective gene, the disease is caused simply because too little of the gene is produced.
Genes are just DNA code that specify particular proteins which are the real machines in cells that carry out the biological reactions. Translating the DNA code into a functioning protein requires cells make copies of the gene sequence, then send the copies to the protein manufacturing part of the cell to make the protein. The number of copies of the gene is controlled so that the right amount of protein is made.
With some diseases, the problem is simply that the gene regulator is broken and not enough copies of it are made. Friedreich ataxia is one example of this where too few copies of the frataxin gene are produced. The protein made by the frataxin gene removes iron and, if there is not enough of it, iron builds up and causes free radical damage, especially to nerve and heart cells.
The group at Laval University Hospital has developed a way to engineer a type of gene regulator (formally called a transcription factor) from a bacteria that normally infects plants. When the engineered gene regulator was put into laboratory cultured human cells, it tripled the number of copies of the frataxin gene. This level of increase should produce enough of the frataxin gene to cure the symptoms for most patients suffering from Friedreich ataxia.
So far, the system has only been used in human cells growing in the lab. To cure the disease, the engineered gene would need to be present in most of a patient's body cells. This is where gene therapy comes in. One way to introduce the engineered bacterial regulator protein would be to use a gene therapy viral vector, such as the adeno-associated virus that is used in the gene therapy drug Glybera which was just recommended for approval in Europe uses.
There are two very unique aspects about the approach the Laval University Hospital group proposes. One, if this was tried in patients, it would be the first time a gene therapy approach is used to regulate a gene rather than just replace or supplement a non-functioning gene. This opens up the possibility to treat many more types of diseases.
The second novelty is that that group is suggesting to use an engineered gene that was made by fusing DNA sequences from bacterial and human genes together. This hybrid gene produces the protein to up regulate the production of more copies of the frataxin gene. Although non-human genes are sometimes used as labels to track delivery of DNA for gene therapy, I believe this would be the first time an engineered gene containing a novel DNA sequence derived from a non-human--in this case a bacteria--would be the functioning genetic element in the potential gene therapy drug.
The current study published in Human Gene Therapy is really just the first step in the development of this sort of treatment but it opens up some intriguing and exciting possibilities.