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Gene Therapy and September Scenes

Today I’m giving an invited lecture at Georgia College, “Gene Therapy: A Forever Fix”?

I’ve given the talk many times, since my book The Forever Fix was published in 2012, but this is the first time I won’t cry. That’s because the first children who have received gene therapy are showing signs of having a future.

Gene therapy as first envisioned decades ago has recently been buried in similar-sounding news.

It’s not the chimeric antigen receptor T cell (CAR-T) technology that FDA approved, as Kymriah, on August 30th. That technology delivers a not-seen-in-nature dual DNA sequence that encodes bits of an antibody and a T cell receptor, acting like an armed drone veering to cancer cells. It’s also not gene editing, which replaces or removes a mutation. Instead, gene therapy adds a gene.


While the research roots of CAR-T technology and gene editing go back years, only gene therapy has actually been in clinical trials for decades. And September has been an historic month.

Corey Haas. (Dr. Wendy Josephs)

• In September 1990 4-year-old Ashi DeSilva received the first gene therapy, for an immune deficiency (ADA-SCID), at the National Institutes of Health. Today she is well, and the therapy, Strimvelis, is approved in Europe.
• In September 1999, 18-year-old Jesse Gelsinger died in a trial of a gene therapy to treat a urea cycle disorder, derailing the field for years.
• In September 2000, a dog named Lancelot was successfully treated for a form of hereditary blindness. That month Corey Haas was born with the human version of the condition.
• In September 2008, Corey, the star of my book, had gene therapy for RPE65-mediated inherited retinal dystrophy. Today a senior in high school, he can see fairly well.

This September is a time for celebration.

In South Carolina, Eliza O’Neill is 7 and just started first grade. Before gene therapy for a form of Sanfilippo syndrome, she could no longer speak. A year and a half later, she continues to try to regain these skills and her parents continue to have hope. They report a happiness and sense of well being in her. The parents kept her at home for nearly 2 years to avoid infection with the type of virus that would deliver her healthy genes. At a biochemical level, she’s improving too. Details are in the middle of this post.

Hannah Sames with Steven Gray.

In upstate New York, just a 10-minute drive from my home, lives Hannah Sames, who also has had gene therapy, for giant axonal neuropathy. She’s grown and can support her body in new ways.

But with both girls, it’s too soon to tell to what degree sending in new genes has helped. Their parents post positive signs on Facebook, indirectly, for it’s hard not to look for improvement, but they know they must be careful with what they say while the effects are being evaluated. That’s typically done once a year – Corey Haas is at Children’s Hospital of Philadelphia right now for his 9th year of checks.


The gene therapy that treated Corey’s blindness, which will be marketed as Luxterna, will likely be the first FDA approved single-gene gene therapy in the US, perhaps even this year. Yet the first gene therapy approved in Europe, Glybera, to treat lipoprotein lipase deficiency, has already been pulled from the market, due to the cost: $1 million. Too few patients, too much money.

The gene therapies in the U.S. pipeline are also bringing staggering price tags. But the cost-benefit calculation must also consider the savings of a lifetime of no-longer-necessary treatments and services, and even the possibility that a patient may feel well enough to earn a living – for many years.

I remember the manufacturer of Glybera comparing future affordable gene therapies to cassette tapes, slipping healthy genes into boilerplate vector systems. That apparently hasn’t happened yet, and at this time of natural disasters and the need to treat more common conditions in the face of uncertain health insurance, ultra-expensive treatments for exceedingly rare diseases may be moving down the priority lists.

Access to gene therapy is another hurdle. Children with rare diseases wait to be admitted to the few slots in clinical trials, as time marches on and their conditions progress. Ironically, the New York Times recently ran an article about too few people volunteering for clinical trials for cancer.

Metachromatic leukodystrophy (MLD) is a very rare disease that is particularly disturbing because gene therapy works, spectacularly so, but only if done before a child develops symptoms – and without newborn screening, that can only happen if an older sibling is sick and doctors then know to test the siblings for the mutation. The U.S. recommended uniform screening panel for newborns doesn’t yet include it. But the successful gene therapy, being pioneered at the San Raffaele Telethon Institute for Gene Therapy in Italy, may finally admit MLD to the list of conditions that are screened for shortly after birth because they are “actionable” if detected early.

It’s hard to imagine the heartbreak. “The only way to find a presymptomatic child is to sacrifice an older sibling to the disease and find a younger sibling in the same family,” Maria Kefalas told me recently. Her daughter, Cal, was diagnosed in 2012, a year before the paper in the Lancet described the gene therapy that is letting a handful of kids live fairly normal lives. The final line of the report honors the older siblings: “In memory of Baily, Valentina, Carlos, Dennis, Liviana, Mustafa, Randa, and Amany.” It’s too late for Cal, but Maria’s efforts continue to bring the gene therapy to others.

As I get ready to give my updated gene therapy talk tonight, on a September evening, I think of the heroes, like Maria Kefalas. Of Lori Sames, who is the Kevin Bacon of the gene therapy community, connecting so many, especially the newly-diagnosed. Of Laura King Edwards and her mom Sharon King, who have gotten rare disease legislation passed and catalyzed gene therapy for the form of Batten disease that will one day take their precious Taylor. And like Steve Gray, who designs the gene therapy vectors that, loaded with DNA cargo, extend or even save lives. And of course a shout out to the health care professionals willing to invest in and bring to their young patients a biotechnology that has been decades in the making.


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