Boeing 747 (Wiki Commons)
Flying a small plane may be easy to learn. Flying a jumbo jet safely, with hundreds of people’s lives in your hands, takes decades of training and testing. Cell and gene therapy today is a bit like a rookie pilot: it will still be some time of carefully monitored trials before it is ready to take us all safely, and reliably, to new treatments.
Gene therapy, in particular, has had its best year yet. Along with the first U.S. approval for a gene therapy for blindness, called Luxturna, there have been promising reports from other clinical trials testing treatments for diseases of the liver, muscles and the spinal cord. What not long ago belonged to science fiction — that you can implant a healthy gene into a person to fix the genetic glitch they were born with — is now a reality. Other gene-directed therapies are also coming. Earlier in August, the FDA greenlighted the first therapy that works to silence a faulty gene, through a process called RNA interference, developed by Alnylam.
These breakthroughs are the result of decades of research, which started in earnest about 40 years ago with the arrival of molecular tools that enabled combining pieces of DNA from different species. Early on, researchers decided that the best way to put a working gene into a patient is to use viruses accustomed to squirting DNA into human cells as a way of life. Then came the gene therapy trials, in the 1990s and early 2000s, which were mired in controversy over patient safety, followed by a decade-long hiatus after a patient died from an immune reaction to a gene-carrying virus.
Questions asked then — how much virus can you safely pump into a person? And is it better to inject the virus directly into the affected organ or into the bloodstream? — are still being asked today and the answers seem to depend on the disease in question.
Although safety has greatly improved overall, the field is not out of the woods yet. Earlier this month, Spark Therapeutics, the company behind Luxturna, announced that two patients in its gene therapy trial for hemophilia A, in which patients lack a blood clotting factor, had to be hospitalized after an immune reaction to the treatment.
And even when therapy gets approved, its eye-watering cost, justified by the drug maker as a way to recoup investment for a one-time treatment, keeps it out of reach for many patients. The price of Luxturna is USD$425,000 per eye.
Setting the cost too high can backfire, as we saw with UniQure’s Glybera, the world’s first gene therapy approved in 2012, in Europe, which came with a price tag of one million euros (CAD$1.5M). Five years later, UniQure withdrew the treatment after struggling to make a profit, dashing patients’ hopes of a promised cure. For gene therapy to become mainstream medicine, drug makers, national health plans and insurance companies will have to find a way to make the new treatments available across the board as much as possible.
A limiting factor is that it is still difficult to grow therapeutic viruses on a large scale. As the virus manufacturing technology improves, it’s reasonable to hope that the treatment price will come down.
But perhaps one of the most ironic obstacles for some forms of gene therapy is that most people are already immune to the viral treatment. The adeno associated virus (AAV), initially coveted for its ability to bring genes into the body without stirring up the immune system, turned out to be too harmless for its own good. Large swaths of people have antibodies poised to destroy the virus, generated after an initial infection, most likely in early childhood. The pre-existing immunity is the main reason patients are turned away from clinical trials and it will restrict who gets treated if and when these treatments become available. That’s why labs are looking to develop other, virus-free gene delivery tools, but when these will reach patients is an open question.
For all its promise and successes so far, gene therapy is still up in the air, clocking up the hours.
My blog is just one of many exploring whether regenerative medicine has “come of age” as part of Signals’ third annual blog carnival. Please click here to read what other bloggers think about this.
Jovana Drinjakovic
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