How gene therapy is transforming medicine

Eileen O’Brien

Siren Interactive

Eileen O’Brien begins Siren Interactive’s five-part rare disease series with a piece exploring the development of gene therapy and how new therapies such as this will affect rare disease patients and the pharma industry.

“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.

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. This was the case with 18-year-old Jesse Gelsinger, who in September of 1999 had also traveled to Philadelphia to undergo gene therapy (for the rare condition ornithine transcarbamylase deficiency) but who died as a result. What caused Jesse’s death wasn’t the working genes but the viruses used to deliver them. Because of this tragedy, the National Institutes of Health (NIH) halted gene therapy trials. Over time, this led to improved protection for participants in gene therapy research.

Gene therapy can be termed a “forever fix” because it cures a problem at its genetic root. This type of gene therapy is somatic, so it permanently affects the patient but will not prevent a defective gene from being passed to their offspring.


“Gene therapy can be termed a “forever fix” because it cures a problem at its genetic root.”


The history of gene therapy includes a variety of rare diseases, such as adenosine deaminase deficiency, adrenoleukodystrophy and Canavan disease.

A disease is defined as rare in the US when it affects fewer than 200,000 Americans at any given time.

A disease is defined as rare in Europe when it affects less than 1 in 2,000.

Why gene therapy for rare diseases?

The National Institutes of Health estimates that there are 6,800 rare diseases and 80% are genetic in origin. “Gene therapy has been pioneered on the single-gene diseases, which tend to be rare,” says Dr. Lewis. “Both because we know the most about them and because it is easier to target a single perpetrator.”

Dr. Lewis offers this analogy, “Imagine a crime committed by a single perpetrator about whom you know a great deal – you have a full description, plus you know where he or she is. This is the situation for a single gene that causes a disease when mutant. Mutations that cause cystic fibrosis, for example, are in a gene on chromosome 7 called CFTR. We know what it is, where it functions and how something goes wrong. In contrast, most medical conditions are caused by small inputs from many genes, plus environmental effects. This is akin to a crime being carried out by several dozen perpetrators, each contributing one small part, whose descriptions and locations may or may not be exactly known.”

“Everything we know about the human condition, we’ve learned from people with rare disorders. Someone is born missing an enzyme or factor, or some other problem, and we figure out how to solve it. We learn from this and move on.”

Timothy Coté, MD, MPH, Professor, Keck Graduate Institute, and Former Director, Office of Orphan Products Development at the U.S. Food and Drug Administration.

Gene therapy has evolved over time as different ways to deliver working genes are experimented with to determine safety and effectiveness. Clinical trials are currently being run by companies ranging from large pharmaceutical companies, such as GSK, to start-ups focusing on gene therapy, such as Bluebird Bio. The trials investigate a variety of rare diseases, including severe primary immunodeficiency, hemophilia, adrenoleukodystrophy and beta thalassemia.


“Gene therapy has evolved over time as different ways to deliver working genes are experimented with to determine safety and effectiveness.”


The power of advocacy

Since gene therapy research is so focused on rare diseases, often the patients, families and advocacy organizations play a key role. For more than 10 years, the National Tay-Sachs &amp, Allied Diseases Association, Inc. (NTSAD) has been making research grants, including some for gene therapy. “In 2007, NTSAD facilitated collaboration amongst a group of global scientists who were all working on gene therapy and provided financial support,” explains Susan Kahn, Executive Director of NTSAD. “In 2009, these researchers were then awarded a $3.5M NIH grant which we continue to supplement with additional funding. NTSAD has stayed involved to help shepherd this research, which is now in late pre-clinical work and hope to start Phase I clinical trials this year.”

The organization has continued to support this project and add value. Kahn notes, “At this point there is no industry support. With a pro bono consulting group, we did an assessment of the commercial opportunity and are using our network to facilitate introductions and its eventual commercialization.”

Another example of rare disease families spearheading gene therapy research is in the ultra-rare disease, giant axonal neuropathy (GAN). When Hannah Sames was diagnosed in 2008 there was no GAN organization, so the family started Hannah’s Hope Fund. Now, a few years later, the Sameses are running a virtual biotech company from their kitchen table. Researchers are ready to start gene therapy clinical trials in nine children at the University of North Carolina at Chapel Hill. To fund the clinical trial will require $900,000, and Doris Buffett has offered a challenge grant of $450,000. The Sames family have until April 30, 2013 to raise the rest of the money.


“…a few years later, the Sameses are running a virtual biotech company from their kitchen table.”


First gene therapy to market

In November 2012, for the first time in the Western world, a gene therapy was approved for sale. The European Commission approved alipogene tiparvovec (Glybera®) to treat adult patients with the rare genetic disorder familial lipoprotein lipase deficiency. The therapy will be available to patients in the first quarter of 2013. Glybera’s developer, the Dutch company uniQure, is preparing to apply for marketing approval in the US and Canada. The company’s website also notes that they plan to apply their adeno-associated viral-derived vectors for therapeutic genes to a large number of orphan diseases caused by one faulty gene.

The future of gene therapy

“I think that gene therapy will be one of many new approaches to treating disease based on knowledge of our genome sequences and gene expression patterns,” opines Dr. Lewis. “It will be especially helpful in treating disease early in the course of pathogenesis, or even before it starts, before cells have been destroyed. Once cells are destroyed, stem cells are a better strategy.”

Kahn says, “Since there is no treatment for Tay-Sachs and often these children die very young, gene therapy gives us hope.”

The next rare disease article in this series can be read here


About the author:

Eileen O’Brien has 16 years of interactive healthcare marketing experience. As Director of Search &amp, Innovation at Siren Interactive, a relationship marketing agency focusing on rare disorder therapies, she oversees search strategy, CRM, analytics, and social media. Eileen was named one of the top 50 women in healthcare on Twitter (@EileenOBrien) and is considered an opinion leader on pharma social media. For more information, email Eileen at, or visit

How will gene therapy affect rare disease patients?