By: Danning Li
On December 19th, 2017, Leber’s congenital amaurosis, an inherited disease that causes severe vision loss and blindness in children met its match in the form of voretigene neparvovec (AAV2-hRPE65v2, or Luxturna for ease of pronunciation), the first gene replacement therapy approved by the FDA for sale in the United States. The previous sentence might contain some words that are not part of the current medical curriculum, but they will become an increasingly important part of our future practice as technology develops. Already, the rate of approval for these novel therapies is ramping up. Last year, the FDA approved three new genetic therapies for public sale (for those interested, the FDA news releases are here in chronological order Kymriah, Yescarta, and finally Luxturna). So, for today’s blog entry, with the possible dawn of the genetic therapy age upon us, let us focus on just what a “gene replacement therapy” is, and why it is such a big deal.
Gene Replacement Therapy
Gene replacement therapy, as its component words suggest, is a treatment that aims to provide a replacement copy of a gene to a patient’s body. It doesn’t matter if the patient doesn’t have this gene, protein or enzyme, or even if the patient has a mutant, non-functional or less-functional version of the enzyme; gene therapy seeks to rectify this issue. The goal of this therapy is for the replacement artificial gene copy to produce a functional enzyme or enzyme subunit that the patient’s own body needs, and can use effectively.
Now, some might be wondering why we don’t just supply the missing enzyme instead, after all, Enzyme Replacement Therapies (ERTs) are well-established treatments for several diseases already. However, the answer to this question is simple: economics. Remember how enzymes are constantly made and broken down in the body naturally? Well, this applies to inherited diseases too since the patient would break down the injected replacement enzymes overtime, and the effects would wear off. Since the replaced enzymes are made in a lab and have to be reinjected into the patient regularly, we would have to constantly produce the purified enzymes and the patient would be on the hook for the rest of their life. This might not sound like such a bad problem, a lot of medications are like this already, right? Unfortunately, it turns out treating someone for decades with regular ERTs cost around USD $9-10 million or more. Insurance companies and OHIP won’t be very happy if a lot of patients started lining up for therapies with these kind of price tags attached.
Looking Towards the Future
Naturally, when faced with such a tantalizingly difficult problem, scientists and physicians thought up a ridiculously simple solution in the 1960s. If making these enzymes outside of the body and then injecting it into the patient is too costly, why don’t we just give the patient’s body the genetic information it needs to make the missing enzymes inherantly? After all, the most efficient enzyme production facility is a living, breathing body that converts regular nutrients into precious enzymes. Even better, if we were lucky enough, and the inserted DNA managed to stick around inside the body somehow, we would have just cured the disease completely, improved the patient’s quality of life, and opened up a completely new world in science. Thus, the idea for gene replacement therapy was born, and brilliant minds around the world would spend the next half a century trying to make this ridiculously simple idea, a reality.
Author: Danning Li
Danning Li completed his BSc. majoring in Physiology at McGill University. Afterwards, he worked for two years on developing a gene replacement therapy for Canavan Disease, a rare inherited leukodystrophy, at the Horae Gene Therapy Center at the University of Massachusetts Medical School. Now a medical student at Schulich, he wants to bring attention to the interesting genetic therapies that will become available in the not so distant future.