“On a bright September day in 2008, 8-year-old Corey Haas went to the Philadelphia zoo with his parents, and screamed. Four days earlier he had gene therapy to cure his hereditary blindness, and now the sun was hurting his eyes.” Corey’s amazing story is featured in The Forever Fix: Gene Therapy and the Boy Who Saved It by Ricki Lewis, PhD.

Corey, who was legally blind, had undergone gene therapy at the Children’s Hospital of Philadelphia for a rare eye condition, Leber congenital amaurosis type 2. Corey underwent an experimental procedure in which viruses bearing healthy genes were injected into his left eye. Only a few days later, he was able to see out of this eye.

The book also tells the story of 18-year-old Jesse Gelsinger, who in September of 1999 had also traveled to Philadelphia to undergo gene therapy (for a rare condition, ornithine transcarbamylase deficiency, or OTC syndrome), but who died as a result. Because of Jesse’s death, the National Institutes of Health halted gene therapy trials. Over time, this led to improved protection for participants in gene therapy research.

What is gene therapy?
At its simplest, gene therapy consists of transplanting normal or working genes to replace missing or defective genes in order to correct genetic disorders. The difficulty is getting the working genes into the body and to the place where they are needed without causing unintended side effects. What caused Jesse’s death wasn’t the working genes but the viruses used to deliver them. The book explains that gene therapy is “the promise of a ‘forever fix,’–a cure that, by fixing problems at their genetic root, eliminates the need for further surgery or medication.” This type of gene therapy is somatic, which only impacts the patient and will not affect their offspring.

The book focuses on rare diseases, mostly in children. As Siren’s founder and president, Wendy White, likes to say, “Innovation happens at the margins.” Dr. Lewis agrees and notes that “understanding how the rare genetic conditions happen can often explain more common ills.” To explain and humanize the complex science, Dr. Lewis uses the compelling stories of patients and families with rare diseases and the researchers who are working to help them. She starts by explaining the history of gene therapy, which was used for the first time in humans in September 1990, at the National Institutes of Health, when 4-year-old Ashi DeSilva received her own altered white blood cells to treat adenosine deaminase deficiency. Ashi and the few others in this trial did well, but it was difficult to prove direct cause and effect since the patients were also receiving enzyme replacement therapy.


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Dr. Lewis describes the evolution of gene therapy over time as different ways to deliver working genes are experimented with to determine safety and effectiveness. Among other stories, she shares the impact of the Odone family (of the movie Lorenzo’s Oil) and the Salzman sisters on adrenoleukodystrophy.

This book resonated with me on many levels. First, I worked at the University of Pennsylvania Health System when Jesse died and I vividly remember this tragedy. Second, a few of these stories detail the long and difficult journey to diagnosis with a rare disease–stories that are, sadly, only too familiar to anyone who works in the rare disease space. Third, the book includes a few people I’ve been fortunate enough to meet, including Jordana Holovach and her son, Jacob, who has undergone gene therapy twice for Canavan disease. Dr. Lewis also details the story of the Sames family, who are about to start gene therapy clinical trials for giant axonal neuropathy–if they can raise enough money by April 2013. Both of these families were also featured in Siren’s book, Uncommon Challenges; Shared Journeys. Finally, it provides hope for the future.

Like many articles I read about rare disease communities, this book made me cry, cheer, shake my head in sheer amazement at what these families have accomplished and, ultimately, left me inspired. I highly recommend reading this well-written book to get a glimpse into the dedicated scientists and pioneering families who are taking medicine to a whole new level.

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