Gene Therapy Is Back And Is Working for Some Patients

[Stephen C Schimpff]

A decade ago there was much hope and hype for gene therapy. Then came the death of Jesse Gelsinger , an 18 year old, as a result of uncontrolled infection from the viral vector used to insert the gene change. That led to a near total stop of gene therapy clinical trials and the development of multiple new regulations, especially multiple levels of extensive reviews. 

Now some new developments are coming to fruition and there is some legitimate reason for enthusiasm that gene therapy may prove viable for some of the most series of genetic disorders.

Some 28 of 30 patients with the rare Lebers’s congenital amaurosis blindness treated with an adeno-associated virus vector delivering a potentially curative gene have had improved eyesight. Gene therapies for two other diseases that cause blindness are under evaluation. 

The much more common hemophilia B is also being studied with a gene therapy given with the adeno-associated virus approach. In this disease, the individual cannot produce the blood clotting protein called Factor IX and so must receive frequent IV infusions The virus with the inserted gene for Factor IX production is given intravenously and goes to the liver where it infects the patient’s liver cells which then produce the needed Factor IX protein.. So far in six patients who have gotten the gene therapy have had Factor IX rise from zero to 2-12% of normal. Low but enough to prevent bleeding in four patients and enough that two others could reduce the frequency of their regular intravenous infusions of Factor IX. 

Kids with severe combined immune deficiency (SCID) have been treated with gene therapy and found to have much reduced infection risk. The same for a few children with Wiskott-Aldrich syndrome, another severe form of immune deficiency. In an NIH sponsored  symposium, (October 7, 2011 issue of Science,) it was reported that 86 patients had by then received gene therapy and been improved. 

There are many issues to be resolved before gene therapy becomes commonplace. Among them are concerns that the viral vector can produce cancer by turning on an oncogene. But, now a decade later, it appears that the promise of gene therapy will become a reality in the not too distant future. Chalk this up to terrific innovation. It will ultimately be a transformative medical megatrend.