When it comes to gene therapy, some people might have an impression of modifying human genes, but it is not this. This treatment introduces genes into cells to produce a certain protein from genes that leads to improvement in the symptoms. Although the effect of treatment may be achieved by administering the protein itself, to continue the effect of the treatment, the protein has to continue being administered because it breaks down too soon. In some cases purification of protein costs a lot which means the drug would be expensive. While gene therapy can continue producing proteins that are required in the target organs by inserting certain proteins into the gene carrier called a vector, hopefully the target organ will obtain the required protein for a long time with fewer treatments required.
First we target the disease such as congenital anomaly that fails the required protein production. Congenital metabolic diseases are an example of when the required enzyme proteins are inadequate; it causes the various symptoms in different genes to occur. In this case, you can improve their symptoms by gene therapy, for example a normal gene expressed in the liver. This may be possible by bone marrow transplant, but there is some risk in choosing a suitable donor and the transplantation process itself. In gene therapy, we could place the cell in which the gene was already expressed into the patient.
The second target is a neuromuscular disease. These diseases will progress slowly and t are in any case caused by the shortage of required protein production. It is not unusual that the protein in a drip doesn’t get into the targeted nerves and muscles. Gene therapy will be able to express the required proteins for nerves and muscles with pinpoint accuracy then those proteins will reach the targeted organs.
The third target is a tumor. However unlike the diseases listed above, it is necessary to kill the tumor. Therefore it is necessary for the tumor to induce the cytoside effect without damaging normal tissues. For that it kills the tumor cells selectively but at the same time it stimulates the immune system response within the defense mechanism.
Because the causative gene has already been identified in hereditary diseases such as childhood, it has been studied how the gene is introduced into a targeted organ, and continues producing proteins regularly. Very good results were obtained in enzyme deficiency metabolic disorders and immune dysfunction syndrome, this is the area that has clearly shown the effectiveness of gene therapy. Also in Europe and America, it has been applied to retinitis disease, improving eye sight to a certain level. However it is true that continuous study is important to secure future safety and long term therapeutic effects. Also international cooperation is needed because the eligible children patient number is limited.
There are examples already started in clinical research and proved effective in animal experiments in neuromuscular diseases, such as muscular dystrophy, neurodegenerative disease (Retinitis Pigmentosa, Parkinson’s disease, etc). Most patients may have already progressed more than a certain level, but there are cases which still have a positive effect. The research and progress of this field is expected because of a lack of drastic treatment and more patients because of an aging population.
Cancer has the highest number of clinical studies. There are various tumor targets. Recently clinical studies of Japan’s own research has been implemented and future development is expected. Particular research which shows that an artificially created virus proliferates only in tumor cells to selectively destroy them, is progressing and has already received approval in the United States for using in clinical trials.Also by inserting the molecules that can combine tumor selectively with attacking just cancer immune cells, has reported amazing results in leukemia.
In addition, research into stimulated angiogenesis in diseases such as chronic Occlusive arterial sclerosis is developing, clinical research for lymph edema, high cholesterol due to an hereditary nature has been conducted.
However, only a few drugs are approved in the real medical field in Europe and America, not many in China and other countries and none in Japan. It is true, however, that a greater range of opportunities for clinical research is now available due to the recent revision of the Pharmaceutical Affairs Law. In the future we assume that authorized gene drugs will be curing patients.
Chiba Cancer Centre Manager of Division of Innovative Cancer Therapeutics
Chiba University Graduate School of medicine Research Institute of molecular and tumor biology visiting Professor