Gene Therapy Clinical Trials By Year

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Table 1 lists the most common clinical targets for gene therapy (http://

Unfortunately, gene therapy clinical trials experienced one drawback after another as several clinical trials failed to show efficacy (Scollay, 2001).

In September 1999, the worst case scenario for gene therapy became reality, when 18 year old Jesse Gelsinger took part in a gene therapy clinical trial at the University of Pennsylvania in Philadelphia. He suffered from a partial deficiency of ornithine transcarbamylase (OTC), a liver enzyme that is required for the removal of excessive nitrogen from amino acids and proteins. Four days after treatment, Jesse Gelsinger died because of multiorgan failure. He was the first patient in whom death could be directly linked to the viral vector used for the treatment. A little later, in April of the following year the journal Science published an article from Maria Cavazzana-Calvo et al. (Cavazzana-Calvo, 2000) where they reported the first definitive cure of disease by gene therapy. Three young children suffering from the fatal X-linked SCID-XI syndrome had developed a functional immune system after gene therapy treatment. After that success several more patients have been treated using the same gene therapy strategy. Some years later 2 out of 11 treated patients had developed a leukaemialike disease obviously as a result of the use of the murine leukaemia virus (MLV) vector (Hacein-Bey-Abina, 2003). After the tragedy of Jessie Gelsinger's death the number of approved clinical trials have decreased worldwide (Fig. 1).

Nevertheless, despite these drawbacks gene therapy research and development itself has never stopped, or slowed down. As a result of that, on October the 16 th 2003, China became the first country to approve the commercial production of a gene therapy. Shenzhen SiBiono GenTech (Shen-

Clinical Trials Gene Therapy
Fig. 1. Decrease in the number of approved gene therapy clinical trials after the year 1999. Edelstein, 2004. Gene therapy clinical trials worldwide 1989-2004 - an overview. Copyright John Wiley & Sons Limited. Reproduced with permission

zhen, China), obtained a drug license from the State Food and Drug Administration of China (SFDA; Beijing, China) for its recombinant Ad-p53 gene therapy (Gendicine) for head and neck squamous cell carcinoma (HNSCC). At the same time there are some very promising ongoing gene therapy clinical trials worldwide for the treatment of diseases such as tissue ischemia (Morishita, 2004), cancer (Trask, 2000, Prados, 2003, Lamont, 2000, Immonen, 2004), haemophilia A or B (Monahan, & White, 2002) and Parkinson's disease (Howard, 2003) with potential for the launching into the market. But so far the American Food and Drug Administration (FDA) has not yet approved any human gene therapy product for sale.

Regarding the variety of areas where gene therapy could be applicable, one notes that only a few are in fact directed to diseases of the central nervous system (CNS). These areas include treatment of brain tumours, e.g. glioblastoma, and degenerative conditions, e.g. Alzheimer's disease and Parkinson's disease, and ischemic brain diseases.

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