While the potential use of genome editing tools such as CRISPR to “fix” genetic diseases has been garnering a lot of attention and excitement, other forms of gene therapy – treating diseases by making genetic changes in a patient’s cells – have made some significant recent progress towards the clinic.
Rather than directly “editing” a disease-causing genetic variant, as in the case of CRISPR, traditional methods of gene therapy work by sending pieces of DNA into the patients’ cells, usually using inactivated viruses as delivery “vehicles.” The DNA will then insert into random locations in the cells’ genome and, if all goes well, carry out its intended function.
In August, the Food and Drug Administration approved the first gene therapy in the United States. The approved therapy, called CAR-T, involves modifying a cancer patient’s T cells (a kind of white blood cells) with a gene for an artificial protein on the cells’ surface. Once placed back into the patient’s body, the modified T cells can then use the introduced protein to track and attack cancer cells.
Then, last week, an expert advisory panel to the FDA recommended that the agency approve a gene therapy for an inherited eye disorder called Leber congenital amaurosis, whose patients are born with severe vision problems. This therapy works by placing functional versions of the defective gene back into the patients’ eyes. If approved, this would be the first gene therapy approved in the US that aims at correcting an inherited genetic condition (two others have received approval earlier in Europe). The company behind this therapy, Spark Therapeutics, is also running clinical trials for gene therapies for a number of other diseases, such as hemophilia.
And earlier in October, a small study was published that showed promising results for using gene therapy to stave off an inherited neurodegenerative disease, called adrenoleukodystrophy. Children affected by this condition, usually boys, may begin to lose physical and cognitive functions as early as the age of 7, and many of them die within a few years.
Despite this progress, there is still some way to go before the promises of gene therapy may be fully realized. For one, it is unclear how long-term would the effect of these therapies be. Many experimental gene therapies have shown decreasing effectiveness over time. This might be due in part to the fact that traditional gene therapy relies on the random insertion of the therapeutic DNA into our cells’ genome, and our cells have a tendency to shut down any foreign genetic materials (including those from viruses) that try to integrate into our genome. The safety of these therapies is also still a concern: the field suffered a major setback in the 1990s due to the death of a patient, and more recently, a number of CAR-T clinical trials were halted or even canceled due to patient deaths. Finally, gene therapy will be expensive, often costing as much as $500,000 or more per dose. Making sure that the therapies are affordable for those who need them will be a major challenge.