New medical treatments, such as gene therapies, have the potential to save lives or completely transform them, to provide hope where there is none, and to justify years of scientific research.
Unfortunately, clinical trials for unproven therapies don’t always end well, especially for those who get started first.
The story of Alissa Feldborg is one of them.
A trial at the University of Massachusetts TH Chan School of Medicine has offered the little girl and her desperate parents a chance to reverse her fatal diagnosis.
But on Easter Monday, 28 months after being treated with energy therapy, 3-year-old Alissa died.
On one level, that was to be expected. Since her parents Thomas Feldborg and Daria Rokina were diagnosed with Sandhoff’s disease when she was 8 years oldmonths, they were told to prepare for his death.
Sandhoff, an ultra-rare genetic disorder, affects previously healthy children by progressively destroying nerve cells in the brain and spinal cord. The child deteriorates rapidly and usually dies by the age of 3.
The trial, which USA TODAY reported on in 2021 as part of a series on rare diseases, gave them a different view of the future, even if the outcome wasn’t what they dreamed of.
“We are heartbroken, but we also realize within ourselves that the battle was lost a long time ago, not now,” Alissa’s father said in a video conversation a week after her funeral. “It’s hard to say, but it ended up being better for her.”
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The promise of clinical trials
Feldborg and Rokina, who live in Copenhagen, Denmark, had read about the UMass trial online and were thrilled when Alissa passed all the requirements to be included.
The researchers were clear that Alissa may not be helping her disease may already be too advanced, the dosage, based on sheep studies, may be too low. As the weeks and then months went by, waiting for the Food and Drug Administration to approve the treatment, their expectations faded.
However, where there’s action, there’s hope, and the pair were grateful to be able to hold on to any sliver.
So, in late January 2021, when Alissa was not yet 14 months old, doctors gave her two doses of gene therapy, one infused into her spinal cord and one directly into her brain.
The first days were promising. For about six months, his deterioration slowed. Her smile is back. She almost seemed there.
“There have been many positive things since this treatment,” Rokina said.
His ability to swallow and cough also improved, which worried his parents. The couple’s greatest fear was that the therapy, intended to correct the genetic error that was poisoning Alissa’s brain, would prolong her life, but not substantially improve her vegetative state.
“When we realized it wasn’t going to cure her, we were afraid it was going to be a long and devastating life for her,” Feldborg said.
How much and how soon?
About 18 months after Alissa’s treatment, the company that sponsored the trial said it could no longer afford to continue. UMass Chan raised funds to continue following the nine children who had already been treated.
Dr. Terence Flotte, dean of the medical school, said in an email that his team plans to try the therapy on one or two more children, bringing the total to 10 or 11.
Some in the study were infants and others were older children with late-onset disease. Newborns show slight improvements and maintain neurological function longer after treatment, Flotte said, while some of the older children experienced a mixed picture with both positive and negative signs.
Gene therapy, which allows children to make the enzyme they need, also appears to be more effective in a closely related disease called Tay-Sachs.
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Alissa had been the first patient fully enrolled. Some later children received higher doses and were treated when they were younger.
“They can stop degeneration, but they can’t heal what’s broken,” Feldborg said of the scientists.
The couple’s only regret is that they couldn’t convince the FDA to be less cautious about the drug. Earlier treatment and a higher dose may have led to a different outcome, Feldborg and Rokina said. They would have happily risked a brain hemorrhage for the chance of a better outcome.
“If we could have changed anything, we would have shouted loud enough for the FDA to hear us.”
Risk is a necessary part of progress
Medicine advances in fits and starts and relies on volunteers like Alissa’s family, said Dr. Francis Collins, a former longtime director of the National Institutes of Health and a lifelong advocate of gene research and therapy.
“I think it’s appropriate to be hugely inspired and excited about the potential” for gene therapy, Collins said.
About 6,500 rare diseases are caused by known DNA misspellings, but cures exist for fewer than 500 of them so far, he said.
As for why therapies like this don’t always work, Collins pointed to biology.
“People don’t appreciate how complicated human biology is,” said Collins, who has spent his career trying to reverse a genetic disease called progeria that causes rapid aging.
Just one or two misspellings in a person’s 3-billion-letter genome can affect trillions of cells throughout the body, including the brain, which are extremely difficult to access with treatments, he said.
With gene therapy treatments like the one Alissa has tried, “you can see the result,” Collins said. “You can’t see how long it is, how many twists and turns, how many unexpected hailstorms will hit you along the way.”
Being among the first patients to receive gene therapy is a challenge for patients and families, UMass’Flotte said in an emailed statement. “Those pioneer patients and families who choose to face such trials first demonstrate great courage, as they make sacrifices for the benefit of those who will come after them.”
Still, gene therapy holds tremendous promise, Collins said.
“I would like people to be optimistic that we’re going to get a lot better at this in the next few years and not feel hopeless or discouraged or pessimistic,” she said.
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Deriving meaning from misery
Over the past six months, Alissa has regressed rapidly.
Her seizures have returned with a vengeance. Breathing became a struggle. Although doctors told them she was unaware of her surroundings, her parents feared she was in pain.
They certainly were. Their lives and those of their four oldest children, three children from his previous marriage and one from hers, were dictated by Alissa’s 24-hour care needs. “I wouldn’t wish that on my worst enemy,” Feldborg said.
Alissa was revived five times in the last three weeks of her life. The sixth time it didn’t work.
Now, each of the boys suffers in their own way and Feldborg and Rokina feel mostly empty.
“No emotions, no happiness. The sun is shining, spring is coming, but you are just indifferent,” said Rokina.
They have no regrets about participating in the process even if the outcome didn’t fulfill their wildest dreams.
Alissa still had a brief bloom after the treatment when she should have seen nothing but decline, Feldborg said.
“What we really hope now is that there is some meaning in her life. They are moving forward with the process,” she said. “At some point there’s going to be somewhere that’s going to be successful and that’s what we’re hoping for. … If that’s the meaning of Alissa’s life, then at least there’s meaning.”
Contact Karen Weintraub at firstname.lastname@example.org.
Coverage of patient health and safety at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial contributions.
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