13. CONCLUSIONS

Gene therapy could be considered as a future approach of treating many genetic diseases and acquired diseases.  Despite the great progress in the clinical trials, the practical reality is still out of reach since there is little evidence of the clinical efficiency of gene therapy.

One of the difficulties involves the discovery of new efficient vehicles, and to translate the gene therapy from the bench to the bedside. For examples success has been achieved in gene transfer for the treatment of Duchenn’s muscular dystrophy of cultured human myoblasts that incorporated into mouse myotubes after intramuscular injection (Mendell, et al 1995). Later studies showed little success in clinical trials mainly due to immune responses (Yang, et al 1994 and Dai et al 1995). More recent studies using newly developed better viral vehicles showed substantial progress (Karpate, et al 1997). Also, the success of gene therapy must involve, appropriate disease target with a gene-delivery system, that have efficient way of gene expression, that produce long-term therapeutic results and little or no toxicity.

However, many of successes of gene therapy involve those diseases, controlled by single recessive genes. This is mainly due to the fact that many of these genes have been cloned.  Therefore, the long-term expression of a normal copy of such relevant gene would correct the abnormality. One of the aspects worth mentioning is the development of new systems of in vivo delivery.  For example the intramuscular injection of DNA and DNA –based vaccines for infectious diseases. (Ulmer, et al 1993) and treating some coronary-artery resterosis (Ohno, et al 1994, Chang 1995). The future of gene therapy for diseases such cystic fibrosis, Dechenn’s muscular dystrophy and other diseases depend on developing and improving gene-delivery systems.  New approaches including methods of modifying adenovirus vectors as well as immunosuppressive tools to prolong recombinant-gene expression in animals (Yang, 1994).

Gene therapy has shown great progress, in recent years and many patients worldwide are subjected to clinical trials in diseases such as cystic fibrosis, muscular dystrophy, adenosine deaminase deficiency (During  et al 1998).  Also acquired diseases as cancer and AIDS were investigated.  Other diseases, are recently considered as a target for gene therapy such as some central nervous system (During & Ashenden. 1998) and diabetes mellitus (Levine and Leibowitz, 1999 Nikol and Fling 1998). In spite of these progresses, the technology still needs to overcome two main problems: the mechanism of gene delivery and control expression of transferred gene.

Some of the recent trials started to investigate the gene therapy by integrating the genetic material into germ cells. This will introduce heritable changes into the offspring of patients. New development now underway to carry out gene therapy in utero i.e. prenatal gene therapy (Jones and Bui 1998, Senior, 1998, Senut, and Gage,. 1999).  These issues have to be thoroughly discussed specially from the ethical point of view (Gordon, 1998).

It could be concluded that gene therapy is now grounded on good scientific principles and the negative results of early clinical trials was mainly due to the early nature of the field. However, recent progress in developing new systems of in vivo or in vitro gene delivery, showed good promise for treatment of a number of diseases.  It is expected that new successes will show up in the near future. However gene therapy raises some important ethical issues specially the germline gene therapy.