Therapy Analysis - Gene therapy - Still the Next Big Thing?
The early years of gene therapy
Following the success of the first gene therapy procedure, it seemed to many as if a new generation of treatment had materialized. Ashanti's case was lifethreatening; lacking even one copy of the gene for adenosine deaminase meant that T-cells in her blood died off, leaving her immune system severely compromised and meaning that even a bout of chickenpox would likely prove fatal. The procedure, performed at the US National Institutes of Health (NIH), consisted of removing her white blood cells, inserting into these cells the missing gene and re-infusing these modified cells back into her bloodstream. The procedure was a success, and led to a normal T-cell count within 6 months and the resumption of a normal 'healthy' lifestyle; however, the process of genetically treating her white blood cells must be repeated every few months, as the therapy only provides a temporary cure.
The case triggered a great deal of hype in both the scientific and lay communities, and despite ethical concerns, it led to the onset of trials evaluating the practicality of gene therapy, with a particular focus on diseases caused by single-gene defects. The 1990s saw a continuous rise, year-on-year, in the number of gene therapy products entering development (Graph 1); a great many companies were eager to launch the world's first gene therapy-based treatment. The death of Jesse Gelsinger in 1999, however, proved to be a major setback for gene therapy research. The patient, who suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver, died from multiple organ failure triggered by a severe immune response to the adenovirus vector; hence becoming the first death attributable directly to gene therapy itself, rather than the underlying pathology it was trying to treat. The US FDA eventually decided that several trial protocols were breached and that Gelsinger should not even have been eligible for inclusion within the trial in the first place; nonetheless the incident could not help but raise worries about this still relatively novel treatment and so led to a more cautious approach to gene therapy research. This and the addition of regulatory changes resulted in a decline in the number of new gene therapy products from 2003-2007, although, interestingly, the number of products making it into late-stage clinical development continued to increase.
