Is the miracle medicine of the future about to become the totally real medicine of the present?

Karen Aiach can tell you everything about the day she learned her daughter was going to die of a rare, incurable disease.

It was a Thursday, early spring, 2005. She and her husband Gad spent the morning packing for a vacation in Normandy. Their daughter, Ornella, was already at the coast with Gad’s parents. Karen remembers wondering if she’d need to pack a rain jacket. She had a lunch date with her mother. Gad called while they were eating, which was strange, because he knew where Karen was and when she’d be home. Maybe this was about Ornella. They’d been waiting for some test results. Maybe it was bad news. Karen remembers not wanting to answer, not wanting to know.

Allo ?”

The doctor wanted to see them right away, Gad said. It was about Ornella.

And it was bad news.

Ornella, Karen and Gad’s first child, was born in January 2005. At her first checkup, the doctor noticed that her liver and spleen were enlarged. It might be nothing, he told Karen and Gad. Let’s see how she’s doing in a few weeks. But Ornella’s organs never shrunk down to their normal size. Not at her second appointment, not at her third. Karen and Gad took Ornella to see a group of metabolic specialists for a battery of tests.

The results came back that Thursday. “Black Thursday,” Karen says.  

Ornella had a rare genetic disorder caused Sanfilippo syndrome. Discovered in 1963 by Dr. Sylvester Sanfilippo, the disease is incredibly rare, affecting only 1 in 70,000 children. It’s caused by a recessive gene, which means both parents have to carry it. Karen and Gad did.

And that meant Ornella was born without the ability to produce an enzyme her body needed in order to break down a type of molecule called glycosaminoglycan. Her spleen and liver, Karen and Gad learned, were engorged because Ornella’s body was suffering a toxic buildup of that one molecule she couldn’t dispose of.

But it wasn’t just her liver and spleen that were affected. According to the specialists, Ornella would never mentally progress past age two.

In short, Karen Aiach’s beautiful baby girl was going to die, and there was nothing she could do about it. Except to invent a cure herself.

She would be incredibly hyperactive and non-verbal every minute she was awake, which would be most of the minutes in the day, because the disease also prevented Ornella from sleeping more than a couple of hours. By age three or four, she would begin to mentally regress, losing her ability to move or communicate. Most patients with Ornella’s type of Sanfilippo did not live past adolescence, the specialists said. And there was no cure, or even an effective treatment.

In short, Karen Aiach’s beautiful baby girl was going to die, and there was nothing she could do about it.

Except to invent a cure herself.

Gene therapy is a relatively young medical treatment. First developed in 1988, it uses a virus to replace missing or defective genes.

That might sound weird–intentionally putting a virus into a sick person’s body–but it’s actually the perfect delivery mechanism. Viruses spread by sneaking into cells and convincing cell machinery to replicate the virus, as opposed to replicating a normal cell. In gene therapy, a person with a genetic disorder receives an injection of a harmless virus that’s been loaded with the “correct” genes. The virus then does what viruses do: Slips into the patient’s cells, and convinces those cells to replicate the virus–along with the correct gene. 

Karen’s not a gene therapy researcher or a medical professional, and she didn’t invent a gene therapy herself. Instead, she started raising money and then set out to recruit Sanfilippo researchers from around the world to help her develop a treatment. She met Dr. John Hopwood, an expert on lysosomal diseases and Sanfilippo syndrome, who was working in Australia. She met Dr. Olivier Danos, a gene therapy pioneer. And as she slowly added experts to her arsenal, she struggled with the “overwhelming sentiment that if no one was doing it, then I had to do it.”

Five years later–a very short turnaround time for any new medicine, much less something as experimental as gene therapy–neurosurgeons drilled microscopic holes into Ornella’s skull and inserted microscopic catheters into her brain. Over the course of two hours, they very slowly injected a virus carrying the genetic code that would create the enzyme Ornella needed directly into her brain.

It was the first European clinical trial in which doctors injected a gene therapy into a child’s brain, and Karen and Gad had no idea if it worked.

Six years later, Karen and Gad still don’t know for certain if Lysogene “cured” Ornella, or even if she’ll surpass the life expectancy for children with her type of Sanfilippo syndrome. That’s largely because gene therapy treatments have more potential for stopping a disease’s progression than they do for reversing the damage that’s already occurred.

But Ornella is different now than before the procedure.

Within days of the surgery, Karen says Ornella was “was quite calm, which we had never seen before.” Initially, they attributed her sanguine behavior to general anesthesia. But as that wore off, Ornella remained calm. The destructive, uncontrollable hyperactivity that had defined her childhood was gone.

“She was very, very peaceful. That was completely new to us.”

“She was just looking around her with her bright eyes as if she was discovering the world around her,” Karen says. “And she was very, very peaceful. That was completely new to us.”

For Karen and Gad, Ornella’s change looks like the good kind of progress. “As parents we are serene and we can see that on an everyday basis, Ornella is a peaceful child, a smiling child. She now has very good nights. And when she wakes up in the morning, she’s just smiling at us with so great a smile that I think we’ve done our job.”

If future Lysogene trials are successful, Ornella won’t be the only person to benefit. In July 2016, Lysogene announced plans for an observational study to prepare for the next step in clinical trials. The treatment isn’t yet ready for market, and likely won’t be for several years. But Lysogene isn’t the only company working on gene therapy, and Sanfilippo syndrome isn’t the only disease genetic engineers are hoping to cure.

The gene therapy field is exploding with activity. Between 1988, when the first gene therapy experiments began, and 2005, the National Institutes of Health tracked 436 gene therapy protocols, which is one step in the process of developing new treatments for consumer use. As of February 2016, the National Institutes of Health was tracking 1,426 therapeutic gene therapy protocols. That’s nearly 1,000 more protocols than the agency saw in the first two decades of gene therapy research.  

But there are still limitations and dangers to the field. While Ornella didn’t experience any complications, other gene therapy trial participants have. In 1999, a young American named Jesse Gelsinger died from an adverse reaction to gene therapy. As a result, federal regulators in the U.S. are very selective about which gene therapy trials they approve for use in humans. Beyond issues of safety and efficacy, there are questions about what impact gene therapy could have on the children of patients who receive the treatments.

Once on the market, the average gene therapy treatment could cost as much as $1 million per patient.

There’s also a price conundrum: Once on the market, the average gene therapy treatment could cost as much as $1 million per patient. The argument for insurance companies paying that amount is that it’s cheaper–if it works–than a lifetime of treatment. British pharmaceutical company GlaxoSmithKline developed Strimvelis, a gene therapy for the severe immune disease that requires some patients to spend their entire lives in plastic bubbles. That treatment costs $665,000 per dose. But it’s not a recurring cost, while the bone marrow transplants those patients currently take are. If these new gene therapies can “cure” genetic diseases, then the gene therapy industry’s argument is pretty simple: the one-time cost for a cure is less expensive than a lifetime of recurring transplants and infusions.

While the U.S. doesn’t yet have a single gene therapy on the market, researchers are finishing clinical trials for an inherited blindness therapy, and there’s another for hemophilia that isn’t far behind. Other researchers are working on gene therapy treatments for depression, fertility, and a slew of other ailments like leukemia, pancreatic cancer, and sickle cell anemia.

Worldwide, there are only four approved gene therapies: China has approved Gendicine to treat head and neck cancers; Russia has approved Neovasculgen to treat Peripheral Arterial Disease; and the European Commission has approved the aforementioned Strimvelis and Glybera, which is for the treatment of lipoprotein lipase deficiency, a rare disorder that causes pancreatitis.

No one can say yet whether gene therapy will dramatically change the way we treat and think about genetic diseases, but unlike just a decade ago, it’s clear this isn’t a flash in the pan.

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