What Constitutes Gene Therapy?
On July 20, a committee of the European Medicines Agency recommended that the Agency approve for routine use in Europe a commercialized, gene-therapy product designed to treat lipoprotein lipase (LPL) deficiency. If the European Medicines Agency acts as expected and finalizes this approval in the next few weeks, this gene-therapy vector will become the first such agent approved in North America or Europe for widespread marketing.
The product, known as Glybera, contains functional, normal copies of the human gene for LPL packaged into an adeno–associated virus vector. Treatment involves injecting small volumes of the gene-carrying virus vector into various locations of a patient’s leg muscles, after which the vector carries the normal genes into muscle cells, which then start producing wild-type lipoprotein lipase, allowing affected patients to gain the ability to digest lipoproteins and avoid fat overload in their blood and the pancreatitis it causes.
The path to gene therapy has been long and rocky, with roots that stretch back roughly 40 years, to the early 1970s when gene cloning first became a reality. Once researchers could isolate and manipulate genes, the concept of putting healthy genes into the cells of patients who carried disease-causing mutated genes was easy to conceive, but turned out to be very hard to execute, especially to execute safely.
Undoubtedly, the biggest bump along the gene-therapy road was the tragic case of Jesse Gelsinger, a 19-year old with ornithine transcarbamylase deficiency who died a few days after receiving an injection of normal copies of the gene packaged in an adenovirus vector at the University of Pennsylvania, Philadelphia, apparently caused by an unexpectedly severe immune reaction that Gelsinger had to the vector.
That misstep alone likely set the field back by a decade, not just for the unexpected technical challenges it raised but also because of the heightened fear and caution it triggered.
But saying that the LPL product now seems on track to become the first widely available gene-therapy medicine may be too semantically parochial.
As I wrote on this blog about a year ago, identification of the genetic drivers of a variety of cancers, and successful treatment of those cancers using drugs selected to target those drivers, is transforming the way cancers are assessed and treated. New reports of advances in this approach now appear in the medical literature nearly monthly.
Treating patients with metastatic melanoma triggered by a mutation in their BRAF gene with trametinib, to cite just one very recent example, may not be the sort of gene therapy that people had in mind when the term was coined or when it’s used today (although the U.S. Human Genome Project agrees that "gene therapy" includes tinkering with how genes are regulated), but as far as I’m concerned, it’s gene therapy, too, and it’s been a huge success that has already entered the mainstream and revolutionized the way medicine is practiced.
–Mitchel Zoler (on Twitter @mitchelzoler)