Selected history of gene therapy

Gene therapy has been defined as a method to treat disease by replacing, manipulating, or supplementing genes (Boulikas, 1998). Therapeutic gene therapy has been defined as the transfer of nucleic acids to somatic cells of a patient to result in therapeutic effect (Ylä-Herttuala and Alitalo, 2003). As compared to traditional medicine, gene therapy offers unique possibilities to treat the genetic causes of diseases. Special hope has been set on treatments for the monogenic diseases.

The treatment of adenosine deaminase enzyme lacking patients with gene therapy showed positive effects (Blaese et al., 1995). This encouraged more research towards gene therapy and resulted in numerous clinical trials. The death of a patient in a gene therapy trial in 1999 (Raper et al., 2003; Couzin and Kaiser, 2005) and induction of leukaemia in some patients in another trial (Hacein-Bey-Abina et al., 2003) have caused the regulatory authorities to tighten the rules for clinical research and directed research to increase the safety of the treatment.

Meanwhile, the use of gene therapy as a supportive method along with traditional treatments has gained promising results for example in the treatment of malignant glioma (Immonen et al., 2004). As gene therapy modifies a complex cellular system with a method consisting of many steps such as delivery, cellular entry, transcription and expression, the limits in the current knowledge are bound to hinder the transfer of this treatment to everyday clinical use. 

Listing of major events

1970 Rogers with his collegues performed the first ever gene therapy experiment by using a rabbit papilloma virus tendency to lower the arginine levels of blood. The treatment of two patients did not result to success and the experiment was criticized to be inadequate.

1980 Cline and collegues performed a beta-thalassemia clinical trial with two patients by using ex-vivo gene therapy. The trial was was seen inadequate and it was performed without necessary permissions.

1989 The first approved clinical trials with patients suffering from the lack of aminase deaminase-enzyme.(Blaese et al 1995). Ashanthi DeSilva (4y) was the first patient which had permanently improved response for gene therapy.The vector used in the trials was based on retroviruses.

1993 The first clinical trial with adenoviruses.

1995 The first clinical trial using adenoassociated viruses.

1999 A patient is lost in a gene therapy trial (Couzin & Kaiser 2005). Jesse Gelsinger was the first patient dying in gene therapy trial. The causes were determinated to derive from poor overall condition of the patient, excess amount of adenovirus vector and direct administration of the drug to the portal vein. The death caused tightening to the regulations concerning gene therapy trials.

2000 The patients treated by Alain Fischer in a SCID-IX immunedeficiency trial show signs of curing. The results were obtained by using retroviruses.

2002 Two out of the treted babies develop leukaemia in the SCID-X trial (Hacein Bey-Abina et al 2003). In most cases, the leukeamia could be treated. It could be shown that the retrovirus-based HIV vector caused uncontrolled growth of blood cells by inserting it's genome to the patients DNA. To day, four of the treated patients have died. (Experiments: France A. Fischer and Great-Britain A. Trasher).

2003 SiBiono GeneTech: Gendicine gene therapy drug gains marketing approval in China. The drug is based on adenoviruses introducing p53 tumor suppressor gene to the cells.

2004 Clinical trials in University of Kuopio by Seppo Ylä-Herttuala give rise to hope of gene therapy for malignant glioma (Immonen et al). Together with thymidine kinase and ganciclovir, malignant cells could be destroyed.These were the first randomized trials in western countries.

2006 Melanoma of two patients can be treated by using modified T-cells, susing gene therapy. The vector was based on retroviruses (Morgan et al 2006).

2006 Shanghai Sunway Biotech: Oncorine gene therapy drug gains marketing approval in China.The drug is based on conditionally replicating adenoviruses. 

2007 A patient is lost in a gene therapy trial for arthritis.The cause was determinated not to be in AAV-vector used in the study.

2008 Treatment of macular degeneration shows positive signs in a clinical trial.