Friday, July 27, 2007

Gene therapy death.

About to hit the news bulletins is another gene therapy death. This is the third. In September 1999 the death of an 18 year-old boy was attributed to gene therapy with an adenoviral vector delivered directly into his liver. He had Ornithine Transcarbamylase Deficiency, an inherited disorder that meant his liver was unable to break down ammonia. Over the following 4 days his condition deteriorated rapidly, and he died a severe immune reaction to the adenovirus.

The second death occurred in a small French trial for X-SCID (the boys-in-a-bubble disease). 12 children in France received gene therapy and four developed acute T cell leukaemia and one died in October 2005. 10 children have been treated in England with a similar protocol have not developed leukemia.

Earlier this week a patient died in an American trial of gene therapy for patients with severe rheumatoid arthritis. The trial involved the administration of an Adeno-associated virus expressing an inhibitor for TNF-alpha. 127 patients have so far been safely treated with this vector. this patient died of acute hepatitis. It is not yet clear what the role the gene therapy played in the death.

Gene therapy remains one of the safest forms of treatment, but as with all experimental therapy there are unforeseen hazards. Thousands of patients worldwide have received various forms of gene therapy, mostly for cancer.

Gene therapy involves introducing a foreign gene into the patient either to replace something that is missing or to invoke an immune response. There are many ways of doing this but commonly a partially inactivated virus is used. Currently many congenital diseases are being treated. Where the missing gene has been identified a virus is used to slip in a replacement copy. Hemophilia, congenital blindness, muscular dystrophy, various immune deficiencies and cystic fibrosis are all disease that show promising early results.

I have sat on the British Gene Therapy Advisory Committee for the past 5 and half years. I am constantly amazed at the quality of the science and equally at the quality of regulation. The people involved in this work are seriously bright and scrupulously honest.


Anonymous said...

Correct me if I'm wrong, but isn't one of the big (potential) problem with gene therapy using a viral vector is that the desired gene gets placed in the nucleic DNA at a random location, leading to the possibility that a gene will be deactivated? I suppose one could get lucky, and the target cells would either be altered innocuously, or 'junk' DNA would be altered, or the cell would undergo apoptosis if it were fatally flawed. However, if my understanding is correct, then gene therapy could lead to some highly undesirable outcomes, couldn't it?

In fact, some researchers suggest that inserted genes preferentially insert themselves in locations that enhance the risk of developing cancer.

Isn't this concept fatally flawed?

Terry Hamblin said...

There are certainly potential hazards of gene therapy, chief of which is the possiblity of inserting the new gene where it could do some damage. Insertional mutagenesis is the term