UPFRONT: The Upsurge in Gene Therapy Trials


“We’re at an inflection point when it comes to cell and gene therapies. These treatments have the potential to address hundreds of vexing human diseases and conditions.” – Scott Gottlieb, MD, FDA Commissioner

Since the 1950s when scientists first discovered viruses’ ability to inject their DNA into host cells, laboratories have been experimenting with using these viral technologies (vectors) to modify human DNA. The idea of using gene therapy to treat human genetic disease was first proposed by Friedmann and Roblin in their 1972 Science article.1 The basic idea behind the technique is simple: put the genetic code that you want into a virus that injects this DNA into a host cell, where the DNA produces the intended effects; making this idea a reality has been difficult.

The first patient treated with gene therapy was a 4-year-old with adenosine deaminase (ADA) deficiency in 1990.2 This quickly led to other trials. These early trials revealed serious therapy-related toxicities, culminating in 1999 with the death of an 18-year-old patient from immune response resulting in multiorgan failure 4 days after dosing.3 This patient, Jesse Gelsinger, had ornithine transcarbamylase (OTC) deficiency that was controlled, and he had agreed to participate to help babies with the fatal form of his disorder. His death was a watershed moment that forever changed the way gene therapy trials were conducted.

Gene therapies are now being approved around the world, and many have steep prices. Luxturna (Spark Therapeutics), approved in 2017 for biallelic RPE65-mediated IRD, was the first gene therapy approved in the United States, based on almost 30 years of work by Jean Bennett, MD, PhD, and Albert M. Maguire, MD, at the Scheie Eye Institute in Philadelphia. Luxturna costs $850,000. A gene treatment for spinal muscular atrophy being developed by Novartis is estimated to cost up to $5 million. It is not surprising, given these price tags, that what was once a trickle of clinical trials has surged into a rush (I have discussed this previously4).

In this issue, we look at the many monogenic inherited retinal degenerations being targeted by numerous companies. The big question is: Can these techniques be used for common diseases like dry and wet age-related macular degeneration, diabetic retinopathy, and tumors? In the future, we may see gene correction and other targeted gene modification techniques using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 nuclease technology enter trials. RP


  1. Friedmann T, Roblin R. Gene therapy for human genetic disease? Science. 1972;175(4025):949-955.
  2. Blaese RM, Culver KW, Chang L, et al. Treatment of severe combined immunodeficiency disease (SCID) due to adenosine deaminase deficiency with CD34+ selected autologous peripheral blood cells transduced with a human ADA gene. Amendment to clinical research project, Project 90-C-195, January 10, 1992. Hum Gene Ther. 1993;4(4):521-527.
  3. Wilson JM. Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol Genet Metab. 2009;96(4):151-157.
  4. Kaiser PK. The genetic lottery. Retin Physician. 2015;12(9):2.

Listen to episodes of Straight From the Cutter’s Mouth with discussion of Retinal Physician articles.