Robin Alderman faces an agonizing reality: Gene therapy might cure her son Camden’s rare, inherited immune deficiency. But it’s not available to him.
In 2022, London-based Orchard Therapeutics stopped investing in an experimental treatment for the condition, Wiskott-Aldrich syndrome. And there are no gene therapy studies he can join.
“We feel like we are the forgotten,” said Alderman, who’s advocated for her 21-year-old son since he was a baby.
Collectively, about 350 million people worldwide suffer from rare diseases, most of which are genetic. But each of the 7,000 individual disorders affects perhaps a few in a million people or less. There’s little commercial incentive to develop or bring to market these one-time therapies to fix faulty genes or replace them with healthy ones. This leaves families like the Aldermans scrambling for help and some trying to raise money themselves for cures that may never come.
“These kids have been unfortunate twice: A, because they got a genetic disease, and B, because the disease is so rare that nobody cares,” said Dr. Giulio Cossu, a professor of regenerative medicine at the University of Manchester in England. “Companies want to make a profit.”
Scientists say this dynamic threatens to thwart progress in the nascent gene therapy field, erasing the potential of a new type of medicine just as a steady stream of research points toward promising treatments for various disorders. Researchers are seeking solutions, often turning to charitable organizations, patient groups and governments.
A major Italian charity announced in February that it’s taking over the Wiskott-Aldrich treatment Orchard had been pursuing. And an arm of the charitable Foundation Fighting Blindness helped launch a company, Opus Genetics, to advance gene therapy work by University of Pennsylvania researcher Dr. Jean Bennett and a colleague.
In many ways, that effort was inspired by patients’ families.
“Some of them have bake sales. One family mortgaged their house to give some money for a study for their rare disease,” Bennett said. “I just feel responsible to help them.”
Families’ pain
The Aldermans have faced years of pain and frustration.
Camden Alderman was diagnosed as a baby with Wiskott-Aldrich, caused by a mutated gene on the X chromosome. It primarily affects boys – up to 10 out of every million — and can cause frequent infections, eczema and excessive bleeding.
When he was a toddler, doctors removed his spleen because of uncontrolled bleeding. As a young boy, he wound up in the hospital many times and was told he couldn’t play baseball.
One treatment is a bone marrow transplant. But he is Black and has Korean heritage, making it difficult to find a donor — people are most likely to match with someone of similar ancestral or ethnic backgrounds. Robin Alderman recalls one doctor saying: “Basically, your son’s only chance at a cure is going to be gene therapy.”
He also told her researchers weren’t then accepting U.S. residents into a clinical trial, which “just kind of broke my heart,” she said.
Today, Camden Alderman is a rising senior at North Carolina Agricultural and Technical State University. He takes penicillin daily and gives himself weekly immunoglobulin infusions under his skin, which help fight infection. Still, he’s landed in the hospital a few times in recent years and has developed a kidney problem.
While he doesn’t view gene therapy as a cure-all, he said, “it would just help me kind of lead an easier life.”
That’s proved true for patients who underwent the experimental therapy, such as Dr. Priya Stephen’s 14-year-old son, who participated in a clinical trial in Italy that accepted Americans at the time.
While Stephen is grateful, she said, she can’t help feeling guilty that her family got an opportunity others don’t: “It’s ethically just not acceptable to have a treatment that we know works, that we know is safe, that people all of a sudden can’t access.”
For a while, it seemed gene therapy for Wiskott-Aldrich was on track for wider availability. Genethon, a French nonprofit research organization, sponsored promising clinical trials but didn’t have funding to continue development, CEO Frédéric Revah said.
Drugmaker GlaxoSmithKline transferred another therapy to Orchard, which announced in 2019 that it had secured a designation from the U.S. Food and Drug Administration meant to speed up development and review. But Orchard discontinued investment in this and two other rare-disease treatments a couple of years ago, with CEO Dr. Bobby Gaspar saying the company sympathized with affected families and would look for other ways to advance the therapies.
“There’s a huge number of diseases out there that could benefit from gene therapy but for which there is no profitability model because the investment for research is high, the cost of production is high and the number of patients is very low,” Revah said.
Most genetic conditions are rare — each affecting fewer than 200,000 people in the U.S. at any given time. Research hasn’t made it past early stages for many of them.
‘Misaligned’ incentives
Financial disincentives plague the process, from drug discovery to development, scientists say.
The amount of work to get from a lab to human testing and through the drug-approval process is “incredibly expensive,” said Dr. Donald Kohn, professor of microbiology, immunology and molecular genetics at the University of California, Los Angeles.
In the last couple of years, he said, gene-therapy investment has largely dried up.
“If you have to spend $20 million or $30 million to get approval and you have five or 10 patients a year, it’s hard to get a return on investment,” Kohn said. “So we have successful, safe therapies, but it’s more the financial, economic elements that are limiting them from becoming approved drugs.”
