Gene therapy makes a slow comeback

Ethical questions are crucial, but they shouldnt stall the progress of this promising branch of medicine

In late November, Reuters reported a milestone in medical history: a gene therapy drug could go on sale in Germany next year, after winning the approval of European regulators two years ago. The drug, Glybera, by a Dutch firm called UniQure currently being scrutinised by Germanys federal joint committee would be the first commercial use of gene therapy in the Western world (China has had a gene therapy drug for a specific form of cancer in the market since 2004). This marks a potential turning point in an area of medicine that has been the subject of highs and lows over more than two decades of clinical trials.

Gene therapy which can involve a number of things, including replacing a malfunctioning gene or introducing a new gene with the ability to fight a disease has been in conceptual development for far longer. Its origins could be said to go back as early as the 1920s, well before the discovery of the structure of DNA, when a British scientist, Frederick Griffith, put forward what he described as the transforming principle; he successfully converted a non-virulent strain of bacteria into a virulent one, after injecting mice with both.

From the late 1960s, when the concept of gene therapy began to involve, it took several decades for the first clinical trial to take place in 1990. A young girl in the US with a genetic defect that had left her with a severely weakened immune system was successfully injected with her own white blood cells containing a corrected form of the malfunctioning gene.

However, the boost gene therapy got following that first successful trial was soon tarnished, in the view of the public, by a tragedy in 1999; an 18-year-old American boy, who had a mild version of a liver condition, which meant his body couldnt process ammonia, died during a gene therapy treatment. This was after a massive response by his immune system to the vector or carrier used to introduce the corrected gene.

The episode raised a number of issues including that of informed consent of those participating in clinical trials as well as the fact that identifying and correcting a defective gene was far from the only challenge facing gene therapy. Selecting the appropriate vector was also vital and not without risks.

Despite predictions that gene therapy would be lastingly damaged by the tragedy, research and trials continued with many promising results for a range of conditions ranging from immune system conditions to cancer, cystic fibrosis, Parkinsons disease and hemophilia.

The renewed confidence in gene therapy is highlighted by the fact that the worlds largest pharmaceutical companies have also entered the market (earlier this week, Pfizer announced collaboration with Spark Therapeutics, a Philadelphia based company on the development of a hemophilia B treatment).

Over 1,700 approved gene therapy trials have taken place in the past two decades, estimated an article on the history of gene therapy in Gene magazine last year with many successes and a few hits. Among the latter were trials conducted in France in 2001 on Severe Combined Immunodeficiency, a condition where the immune system is so crippled that in one case it required a boy to live in a germ-free bubble. Several infants involved in the trial subsequently developed leukemia, though other clinical trials for gene therapy since have been successful.

There have been some understandable public concerns about gene therapy and its impact on the one hand it offers that tantalising potential of curing some of the most lethal conditions while on the other, tampering with genetic makeup is something that has long conjured up fears in the public imagination of genetic engineering and exacerbating discrimination against those with disabilities and disease.

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Gene therapy makes a slow comeback