MIT Technology Review (March/April 2017) lists “Gene Therapy 2.0” as one of the 10 Breakthrough Technologies of 2016. I was intrigued to see this technology listed as “breakthrough” in 2016, since it had been studied for decades. The results of this therapeutic approach were mostly negative, marked in particular by the death of 18-year-old Jesse Gelsinger in a clinical trial in 1999. Recent developments, however, have brought gene therapy to the forefront of combating life-threatening disorders, including rare diseases. Because of my specific interest in rare disorders and the special challenges they pose in drug development, this re-emergence of gene therapy as an effective tool is particularly exciting.
The theory behind gene therapy entails treating patients who have defective genes with copies of healthy genes, using viruses as a delivery tool. The delivery system posed an obstacle in early studies by having serious deleterious effects on patients, including cancer, multiple organ failure, and brain death. Many such challenges have been overcome in recent times, as exemplified by the approval of two gene therapies in Europe for treatment of inherited diseases: Glybera for lipoprotein lipase deficiency, approved in 2012; and Stremvelis for a form of severe combined immune deficiency (SCID), approved in 2016. Potential therapies in the US that could get approved in 2017/ 2018 include a therapy for a progressive form of blindness from Spark Therapeutics; gene therapies for treating hemophilia and epidermolysis bullosa are also under development. According to a pediatrician and scientist at Stanford University, clinical trials of gene therapies to treat 40 to 50 different diseases are ongoing.
While considerable developments have been made in gene therapy research, challenges still remain, particularly in treating diseases with more complex molecular physiology, e.g., Alzheimer’s disease and diabetes. For rare diseases and/or diseases with deficiencies in single genes, however, gene therapy already appears very promising.