Just a little more than a year after Miracle film producer Gordon Gray and his wife Kristen learned both their young daughters Charlotte and Gwenyth were afflicted with the rare and fatal brain disease Batten CLN6, Gray’s desperate race against time for a cure has led to a potential medical breakthrough. The girls were the pioneer recipients of the first gene therapy of its kind in humans in a clinical trial begun at Nationwide Children’s Hospital in Columbus, OH. Gray tells Deadline that he is already seeing signs of a rebound in Charlotte, the 5-year old whose motor and verbal skills were eroding at a heartbreakingly fast rate.
In March, Charlotte was given the equivalent of a magic bullet: a virus infused with the healthy CLN6 gene that was missing from her brain, and which allows cells to purge built-up wastes and restore balance in the brain. That virus was introduced intrathecally into Charlotte’s spinal fluid, for a short ride to her brain. This was done almost exactly a year after the Grays were given the death sentence diagnosis by doctors and told there was nothing to be done except prepare for Charlotte to go blind, lose her motor and verbal functions and ability to feed herself, progressing to eventual death between ages 6 and 12. And then prepare to live the same nightmare once again, because even though Charlotte’s younger sister Gwenyth hasn’t shown symptoms, she too was diagnosed with the rare brain disorder. Gwenyth was given a preventive dose of the gene therapy clinical trial last week.
I’m telling the readers of Deadline all this because Gray entrusted this publication with his story last year, one of several things he did to rage against the unacceptable hand he’d been dealt. This is a long follow-up story, but it is one that the influential readers of Deadline in the Hollywood community helped to make possible, by building a $3.5 million war chest through donations that allowed Gray to do something normally reserved for Liam Neeson in a movie like Taken. How many times in your life do you get to be even a small part of what might turn out to be a miracle?
Charlotte’s deterioration has been halted, and she has begun to show slow signs of recovery. There are no guarantees in life, but the producer of so many inspirational underdog sports movies, who told Deadline last June that he needed a Doug Flutie-like Hail Mary pass to save his daughters, is cautiously optimistic this breakthrough may in fact have saved both their lives. But the ongoing trial is expensive, and he has pledged to help four more children who are lined up to receive the treatment by the fall. Another six, maybe more, are out there in the world, also hoping for a chance to stop the disease’s progression. So Gray continues to try and rally financial support and the appeal can be viewed here for what he feels could be an historic medical breakthrough for children afflicted with Batten CLN6 and other similar brain diseases.
“The news is good,” Gray said. “We fought really hard after being told Batten was rare, fatal with no cure and when we refused to accept that, we were told even if you want to get FDA approval to get a clinical trial going, it would take five to six years. We didn’t have that time and we’ve managed to get something done. The doctors won’t say they treated anyone because it’s all investigational, but Charlotte was the first patient in the clinical trial on March 10. This past Friday, April 22, we entered my second daughter Gwenyth, into it. I’m so grateful to have gotten to this point but it feels like we’re starting from day one again. We need to keep this trial going, and Charlotte has lost so much ability because of this disease.
“I used to call her the mayor, because she never stopped talking, and she knew everyone’s name,” Gray said. “She went from being that kind of child to, right before we entered her into the trial, being down to one-word sentences, with no word more than two syllables. She’d gone from this girl who’d get on her little scooter going up and down the beach to having real difficulty walking. There’s receptive and expressive communication, and she seemed to understand most of what I say to her, but she has difficulty communicating and it’s only because we spend so much time with her that we understand what she wants,” Gray said. “The one thing about Charlotte is she was a happy vibrant child with a big expressive personality and hasn’t lost any of that joy and happiness, despite the difficulties walking, talking and eating and going through her daily life.”
Things have improved since the treatment that have given the Grays real hope for the first time in a long time.
“She seems to be making progress,” Gray said. “It seems like she’s more present, more engaged; she’s joking a little bit, in her own way. If there’s a song that mentions happy, she’ll say, ‘no, sad,’ and laugh. That’s her way of joking. She’s sitting up a little straighter, and she’s walking better. Doctors and especially scientists, they are very conservative, but I’m incredibly hopeful and they are optimistic and that’s the best they are going to give me. But she is making strides. If this worked, and God I hope it did, we now have to just put her back together. There’s something called Neuroplasticity, where the brain can sort of rebuild itself. But the first thing we had to do was arrest the progression of the disease.”
When Gray first publicly discussed his daughter’s condition last June, he did so to promote awareness that a number of stars, from Rihanna to Dwayne Johnson, Mark Wahlberg, Channing Tatum, Jon Hamm, Seth MacFarlane, Jennifer Garner and athletes like Andrew Luck and U.S. women’s soccer star Alex Morgan were going to ask their Facebook followers to donate $1 for the search for a cure. Back then, the best chance seemed to involve funding a New Zealand researcher who created a vector virus that was effective in curing a sheep of the affliction. As the donations accumulated, Gray discovered the problem with these research efforts was, they weren’t moving quickly enough and wouldn’t be ready in time to help Charlotte.
“It was difficult to find anybody that was on my timeline,” said Gray, who quickly became knowledgeable in the science of childhood brain abnormalities. “I wanted this done yesterday and they thought I was crazy.” With the help of a team of consultants, Gray boiled their best chance down to gene therapy. “The approach seemed to make sense on paper for this particular variant of Batten, and I could understand theoretically how it might prevent the progression of the disease, or stop it altogether. There were a lot of things I didn’t understand, a lot that didn’t make sense to me or a lot of experts, for that matter. But this seemed to make sense to everybody.”
Then came the miracle Gray was looking for, in the form of a doctor named Brian Kaspar, another named Jerry R. Mendell and a third named Emily C. De Los Reyes. They had taken Spinal Muscular Atrophy to clinical trial and even though this had nothing to do with Batten CLN6, there was a common thread.
“I asked Brian if he would be willing to pursue a clinical trial with the girls and everyone else afflicted with this disease, and when I got on the call, he wasn’t even really familiar with Batten,” Gray said. “He said he would look into it, and based on some of the work he’d done with SMA, he was not unfamiliar with gene therapy, something he was pursuing. He asked my daughters’ names, and told me, ‘I too have a daughter named Charlotte.’ It felt like maybe we might get a little magic going here and we set a call for the following Monday. I started that call by telling him I would not take no for an answer, and he said, ‘you won’t have to.’ He’d done his research on Batten. One of the things we were fortunate about, is the gene for CNL6 is a similar size to the SMA gene. So it would fit into the vector they created, which allowed us a shot at success for creating a vector for Batten. If it had been too big, that could have been trouble. Brian decided he was going to do everything he could to help us. He said, ‘my lab is fully funded and I will not charge you anything more than what it costs.’ A lot of people I’d spoken with before, it seemed what they were asking was double and triple the price it ultimately costs to go to trial, and it felt like they always wanted the money upfront. With Brian, I would have to call him and say, hey, can I send you some of this money?”
Gray said it came down to this attack strategy, approved by the FDA after it was felt that the treatment would be safe: “My daughters are missing a healthy CLN6 gene. They don’t have it and if you are missing that gene, they need to replace it. That gene makes a protein that is essential for neurons in the brain to be healthy. So the doctors made a vector, essentially a virus that has all the harmful elements clipped away. You essentially insert the missing gene into that virus. What everyone knows about viruses is, they go viral. So there’s this virus called the AAV9, which is exceptional about spreading to the brain. They put that missing gene into the virus, and they delivered it intrathecally with a lumbar punch, through the spinal fluid, and that goes into the brain.”
One of the strengths of this course of action is that it’s a one-time treatment, for the most part. “Because it’s a virus, your body will build up an immunity to it,” Gray said. “Therefore, it’s contemplated right now as being one and done. With this type of treatment, this investigational new drug, this should be it for my daughters. They’re thinking maybe down the road you could get another dose of this, but that’s not something we’re thinking of for the immediate future.”
Gray sees signs of improvement in Charlotte, and even though he’s made a career out of producing movies with happy endings, he said all this constitutes just one giant step on a long road. “There are no biomarkers to see if the therapy worked,” he said. “It’s like if someone put a bomb under your table and you try to defuse it. The only way you’re going to know you haven’t been successful at defusing the bomb if it blows up. The only way we’ll know if the treatment for my youngest daughter Gwenyth didn’t work is if she starts to decline. And the only way I’ll know with Charlotte is if she becomes overtly better, or she starts to decline again. You just have to wait.”
Gray said he is so thankful to Disney, where he has his first-look deal, for allowing him to spend almost every waking moment of the last year in this race against time. The ordeal isn’t over, though, because this trial needs to continue and those other children facing the same hopeless fate need their shot at a miracle. And Charlotte needs to be brought back from a descent caused by what Gray said is a most relentless disease. So as grateful as he is, Gray is prevailing on Hollywood to dig into their wallets one more time.
“What they need to get it approved as a drug is Proof of Principle,” he said. “It has to be efficacious. My two girls are the pioneers right now and there’s another child coming up in June, and we’re trying to fun three more patients in November. There are maybe 10 kids right now, but as this trial is becoming more public, we’re finding out there are kids all over the world with this. It’s expensive therapy and we’d like to be in the position to cover these kids and so we’re still fundraising to support the clinical trial. And with Charlotte, we need to rebuild her and I’d like to create a center, an equivalent of a school for kids with brain injuries that need their brains to be rewired. Charlotte is going to therapies at six different locations and it would be great to put them under one roof where we would recreate the environment of a school. Not just for Batten kids, but for someone who has been in a car accident, or fallen off a ladder, so we help rebuild the brains of injured children. That’s something for down the road. There’s this technology called Crisper, and I’m telling you, whoever cracks the code and solves it will win the Nobel Prize. It’s essentially, if you have a broken gene, they fix it.
Gray, who said his hair has turned the color of his name and who now wears glasses to read, said it feels like the last year has unfolded like one long day. He couldn’t have scripted a better outcome at this point, but his long day is far from over, he realizes.
“We need $1 million by October to continue our funding commitments,” he said. “I was unfortunate, and my girls were unfortunate to be faced with this disease. But we couldn’t have made any of the progress we did without the support of my friends in the film community. It is pretty incredible what we have been able to do with the fundraising and awareness, and for that I am truly grateful. Getting that news on that day last year, being told your daughter has this fatal disease and there’s nothing you can do, I don’t want any parent with a child who has Batten CLN6 to hear that. I want it to get the point where when they’re told, this is what you do, and here is where you sign up.”