Medical gene therapy

The theoretical complications posed by random chromosomal integration became a medical reality in 2002, when two children who had received retroviral-based gene therapy 2 years previously developed a leukaemic-like condition. The initial clinical trial aimed to treat X-linked severe combined immunodeficiency (SCID-X1), a hereditary disorder in which T-lymphocytes and NK cells in particular do not develop, due to a mutation in the gene coding for the yc cytokine receptor subunit. The clinical consequence is near abolition of a functional immune system. 

Gene therapy is not, and will not be, an inexpensive therapeutic tool. The cost of such treatments will likely be broadly similar to the cost of present-day biopharmaceuticals. However, if proven successful in treating many currently incurable conditions, the cost beneht ratio will almost certainly greatly favour its medical use. 

Gardlik, R., Palffy, R., Hodosy, J., Lukacs, J., Turna, 1, and Celec, P. 2005. Vectors and delivery systems in gene therapy. Medical Science Monitor 11(4), RA110-RA121. 

Gene therapy is under study to determine whether it could be used to treat disease. Current research is evaluating the safety of gene therapy future studies will test whether it is an effective treatment option. Several studies have already shown that this approach can have very serious health risks, such as toxicity, inflammation, and cancer. Because the techniques are relatively new, some of the risks may be unpredictable however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research is as safe as possible. 

An Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC) must approve each gene therapy clinical trial before it can be carried out. An IRB is a committee of scientific and medical advisors and consumers that reviews all research within an institution. An IBC is a group that reviews and approves an institution s potentially hazardous research studies. Multiple levels of evaluation and oversight ensure that safety concerns are a top priority in the planning and carrying out of gene therapy research. 

We have included gene therapy and stem cells to present a more comprehensive perspective on medical treatments, although they are not drugs by our conventional definitions. 

The potential contribution of stem cells to medical treatment lies in then-capability to differentiate and grow into normal, healthy cells. Using pluripotent stem cells, scientists are devising means to culture them in the laboratories and coax them to grow into various specialized cells. Rather than gene therapy, with stem cells we have the potential of cell therapy to repair our diseased tissues and organs. This will circumvent the lack of donor organs. Stem cells also provide the possibility for healthy cells to cure disabilities such as strokes, Parkinson s disease, and diabetes. 

The Institute of Cancer Research, Surrey, UK Mitchell J. Frederick Department of Head and Neck Surpfcry, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA Rossella Galli Neural Stem Cell Biology Unit, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy Thomas M. Grogan Medical Innovation, Ventana Medical Systems, Inc, Tucson,... 

To date (mid-2002) no gene therapy based product has thus far been approved for general medical use (Chapter 11). Although gene therapy trials were initiated as far back as 1990, the... 

Despite all the hype, it is important to note that, by mid-2002 at least, only a single nucleic acid-based product has been approved for medical use (an antisense-based product, discussed later). No gene therapy-based product had been approved for general medical use by that time. 

Moreover, gene therapy — like all other medical interventions — is not without associated risk. A US patient died in 1999 as a result of participating in a gene therapy-based trial. Even more disturbingly, the ensuing FDA investigation unearthed allegations that at least six other... 

To date, the majority of gene therapy trials undertaken aim to cure not inherited genetic defects, but cancer. The average annual incidence of cancer reported in the USA alone stands at ca. 1.4 million cases. Survival rates attained by pursuit of conventional therapeutic strategies (surgery, chemo-therapy, radio-therapy) stands at about 50%. Gene therapy will likely provide the medical community with an additional therapeutic tool with which to combat cancer within the next 10-15 years. 

Every few decades, a medical innovation is perfected that profoundly influences the practice of medicine. Widespread vaccination against common infectious agents and the discovery of antibiotics serve as two such examples. Many scientists now believe that the potential of gene therapy and antisense technology rivals even the most significant medical advances achieved to date. 

ITABLE 15.1. Medical conditions that could benefit from cell and gene therapy... 

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