Gene therapy consists in treating a patient suffering from a genetic abnormality by introducing into his body the “healthy” copy of the defective gene. For this, the researchers have developed a clever technique: the gene is carried by a virus!
“Viruses have developed the capacity to attach themselves to foreign cells and to use their” machinery “to multiply after having injected their genetic material into them”, explains Dr. Philippe Moullier, scientific director of Généthon (laboratory funded at more 90% by the Telethon). In this area, the AIDS virus and its derivatives, adenoviruses and parvoviruses prove to be the most effective. Rest assured, they were shaped in the laboratory. And drastic testing is done to make sure they won’t transmit any disease to humans. In gene therapy, these modified viruses are called vectors.
Two ways to proceed
To introduce the drug gene into the patient, one proceeds either directly: the vector is injected into the diseased tissue (for example: the retina); or indirectly: the patient’s cells are removed, processed in the laboratory and reintroduced into the body. Depending on the pathologies, the quantity of vectors, the number of injections and their location vary. The whole difficulty is to obtain a lasting effect over time.
Genetic diseases affected by gene therapy
Today, it is easier to try gene therapy on localized pathologies or monogenic diseases (only one gene to be corrected). For example, immune deficiencies. Thus, the nine bubble babies treated by the team of Prof. Alain Fischer, head of the immuno-hematology service at the Necker-Enfants Malades hospital in Paris, are considered to be cured, after ten years of hindsight. But we must remain cautious about their long-term future. “The results were beyond our imagination, it worked really well. Proof was made that gene therapy worked, ”exclaims Prof. Marina Cavazzana-Calvo, head of the biotherapy department at Necker hospital.
Conversely, neuromuscular diseases such as Duchenne muscular dystrophy pose difficult problems to overcome. We must manage to treat all the muscles, which requires 100,000 times more vectors than for a retina.
Non-genetic pathologies also concerned
The majority of gene therapy clinical trials focus on diseases that are not strictly speaking genetic. Thus in cancer, the use of killer genes is being developed which attack cancer cells. There are even ongoing trials in cardiovascular disease.
In France, Prof. Éric Van Belle, cardiologist at Lille University Hospital, conducted a trial on around 100 elderly patients suffering from inoperable leg ulcers. They were injected into a muscle in their leg with a gene that stimulates the growth of new blood vessels. After a year, there was a 50% reduction in the risk of amputation and 50% in mortality, and “the ulcer returned to an acceptable chronic stage”, according to Prof. Van Belle. This trial will be extended worldwide on 500 patients.
Obstacles to the development of gene therapy
The first concern with gene therapy is that the gene-drug will get into the wrong place and activate an “oncogene”, which promotes the development of cancer. This is what happened with some bubble babies and which led in 2002 to the suspension of the trials conducted by Professor Alain Fischer’s team at the Necker-Enfants Malades hospital in Paris. New clinical trials, using safer modified viruses, are expected to start soon.
A risk of treatment intolerance
Another problem: the tolerance of the treatment. Indeed, gene therapy can be compared to a transplant since foreign elements are injected into an organism. “We are now at the same stage as organ transplantation. The issues are the same. In some cases, it will be necessary to consider administering immunosuppressive drugs to patients, ”notes Dr. Philippe Moullier, Scientific Director of Généthon.
Medicines already developed
The first drug to receive marketing authorization (MA) in 2004 is a Chinese drug, Gendicine®, intended to treat head and neck cancers.
A Dutch laboratory has also obtained Marketing Authorization for Glybera®, which transfers a gene capable of reducing lipids in the blood.
In France, a temporary authorization for use has been issued for Cerepro®. This medicine has been given to a patient with glioma (a cancer of the brain). A marketing authorization procedure is underway with the European Medicines Agency. It is the same in Ada-Scid, a serious immune deficiency, the request coming from an Italian team.