A watershed moment in gene therapy has finally come to pass. This month, a committee from the European Medicines Agency recommended the approval of a gene therapy drug, named Glybera (alipogene tiparvovec), for the treatment of a rare inherited genetic disorder. Final approval is now in the hands of the European Commission, which could take up to 3 months to complete, but it is believed that the drug will be approved for sale, the first time ever in the Western world.
And with its approval, the floodgates for gene therapy could be opened.
Fundamentally, gene therapy supplies the body with healthy genes to compensate for missing, deficient, or defective genes. Humans are believed to have between 80,000 essential proteins coded by between 20,000 to 30,000 genes, and while some genetic mutations can be tolerated, others are incredibly detrimental.
Case in point: the familial disorder known as lipoprotein lipase (LPL) deficiency affecting 1 to 2 persons per million, which is caused by mutations in the gene that codes the LPL enzyme. The function of this enzyme is to hydrolyze triglycerides into free fatty acids, an essential step in the metabolism of fats from consumed food. However, the inefficient breakdown of triglycerides leads to a massive accumulation in the blood, so much so that Dr. Daniel Gaudet at the University of Montreal told The New York Times, "It's the equivalent of having 10 percent cream in your bloodstream."
These fats can fill macrophages to form small to large nodules under the skin called xanthomas. The condition also produces severe abdominal cramping and acute inflammation of the pancreas (pancreatitis) caused by clumps of fats particles blocking capillary flow.
To date, individuals who suffer from LPL deficiency have had little choice but to highly regulate their dietary fat intake lest they end up in the hospital.
But getting to this stage has been a challenging journey for Glybera as gene therapy has struggled to get traction among drug regulators. The drug's maker, Amsterdam Molecular Therapeutics, ran clinical studies on the drug in both the Netherlands and Canada which showed that the drug performed well among the 27 patients tested. December 2009, the company filed for Glybera's approval, but after back-and-forths with regulators, the Committee for Medicinal Products for Human Use decided that it couldn't back the drug because too few patients were enrolled in the trial to establish long-term data of its effectiveness and safety.
Reaction to the ruling caused the company's stock to plummet. After an attempt to raise funds, the company announced in February that part of its business would be acquired by a newly formed private company called uniQure and the public company would be liquidated. Two more attempts were made to get Glybera passed, both of which were rejected. But a compromise was found by limiting commercial availability of the therapy only to those individuals with the most severe manifestations of the disease (less then a thousand people worldwide), and the Committee reversed its last decision to give the drug the green light.
Unlike medications which are quickly metabolized, gene therapy incorporates the functional gene into the patient's DNA. In the case of Glybera, this means that a single injection of the drug can help produce the missing LDL enzyme for years, though it is not known exactly how long.
To demonstrate how gene therapy works, the University of Amsterdam commissioned an excellent animation, and though it is about the liver, it is highly applicable to the way Glybera works:
There's little doubt that gene therapy will be an important component in the future of medicine, but whether or not approaches can be developed that are as safe and effective as pharmaceutical drugs remains to be seen. In 2003, China's State Food and Drug Administration approved a gene therapy called Gendicine to treat head and neck cancer0, and since has approved two others, Oncorine and Rexin-G. However, skepticism about the safety of that drug has led to nearly a decade of failed attempts to get a gene therapy past regulatory hurdles in Western Countries.
Over the past year, studies with various gene therapies have shown them to be highly effective in stopping bleeding in hemophilia patients and treating Parkinson's symptoms. A recent follow-up on 43 HIV patients who received gene therapy 11 years ago found all of them to be healthy. There's even clinical trials demonstrating the success of gene therapy in helping the blind to see again.
Many of these treatments have been waiting in the wings because no gene therapy had received approval in Europe and North America, so Glybera's approval is reason for many drug companies and researchers to celebrate. Exactly how fast and how broadly applicable gene therapies will make it to the masses remains to be seen, but it will likely follow a familiar path for emerging technologies: slow at first followed by exponential growth.
The genetic modifications of the science fiction world are perhaps decades away for most but for a few hundred people in the world today suffering with LDL deficiency, it is a reality right around the corner.