by Robin Alderman is faced with a painful reality: gene therapy could cure her son Camden’s immune deficiency. But it is 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 participate in.
“We feel like we’ve been forgotten,” said Alderman, who has been praising her 21-year-old son since he was a baby.
Altogether, about 350 million people worldwide suffer from rare diseases, the majority of which are genetic diseases. But each of the 7,000 individual disorders affects perhaps a few million people or less. There is little commercial incentive to develop or bring to market these one-off therapies to fix faulty genes or replace them with healthy ones. This leaves families like the Elders looking for help and some trying to raise money themselves for medicines that will never come.
“These children were doubly unfortunate: A, because they got a genetic disease, and B, because the disease is so rare that no one cares about it,” said Dr. Giulio Cossu, professor of medicine regenerative at the University of Manchester in England. “Companies want to make a profit.”
Scientists say this dynamic threatens to block progress in the older field of gene therapy, destroying the potential of a new type of medicine just as a steady stream of research points toward promising treatments for various disorders. Researchers are looking for solutions, often turning to charities, patient groups and governments.
A large Italian charity announced in February that it is taking over the Wiskott-Aldrich treatment that Orchard was following. And part of the charity Foundation Fighting Blindness helped launch a company, Opus Genetics, to promote gene therapy work by University of Pennsylvania researcher Dr. Jean Bennett and a colleague.
In many ways, that effort was driven by the patients’ families.
“Some have bake sales. “One family mortgaged their house to give some money to study their rare disease,” Bennett said. “I feel responsible to help them.”
Family pain
The Elders face years of pain and frustration.
Camden Alderman was diagnosed as a child with Wiskott-Aldrich, due to a mutated gene on the X chromosome. It mainly affects boys – up to 10 in a 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 ended 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 of Korean heritage, which makes finding a donor difficult – people are more likely to match with someone of similar ancestral or ethnic backgrounds. Robin Alderman recalls one doctor saying: “Basically, your son’s only chance for a cure is gene therapy.”
He also told her that researchers weren’t accepting US residents at the time in a clinical trial, which “broke my heart,” she said.
Today, Camden Alderman is a rising senior at North Carolina Agricultural and Technical State University. He takes penicillin every day and gives himself weekly infusions of immunoglobulin under his skin, which helps fight infection. However, he has been hospitalized several times in recent years and has developed a kidney problem.
While he doesn’t see gene therapy as a complete cure, he said, “it would help me live an easier life.”
That is true for patients who underwent experimental therapy, such as Dr. Priya’s 14-year-old son Stephen, who participated in a clinical trial in Italy that accepted Americans at the time.
Although Stephen is grateful, she said, she can’t feel guilty that her family got an opportunity that others don’t: “It’s ethically acceptable to get treatment that we know works, that we know are safe, that people are all. suddenly it can’t be accessed.”
For a while, gene therapy seemed to Wiskott-Aldrich to be on track for wider availability. Genethon, a French nonprofit research organization, sponsored promising clinical trials but lacked funding to continue development, CEO Frédéric Revah said.
Drugmaker GlaxoSmithKline has moved another therapy to Orchard, which announced in 2019 that it had received a designation from the US Food and Drug Administration meant to speed up development and review. But Orchard stopped investing in this treatment and two other rare treatments a few years ago, and CEO Dr. Bobby Gaspar that the company sympathized with affected families and would look for other ways to promote the therapies.
“There are a large 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,” said Revah.
Most of the genetic conditions are rare – each affecting fewer than 200,000 people in the US at any given time. Research did not make it past the early stages for many of them.
Lacey Henderson’s daughter, 5-year-old Estella, has alternating hemiplegia of childhood, a neurological condition that affects 300 people in the United States. Henderson said. Medicines can relieve symptoms, but there is no cure.
Her Iowa family raises money through GoFundMe and a website to develop gene therapy. They have brought in about $200,000.
“We have three different projects with different researchers,” Henderson said, “But the problem is that everything is underfunded.”
‘Misaligned’ incentives
Financial incentives drive the process, from drug discovery to development, scientists say.
The amount of work that needs to be done from laboratory to human testing and through the drug approval process is “extremely expensive,” said Dr. Donald Kohn, professor of microbiology, immunology and molecular genetics at the University of California, Los Angeles.
Over the past few years, he said, gene therapy investment has largely fallen.
“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 there are more financial, economic aspects that are restricting them from being approved drugs.”
Ultimately, most biotech companies become public and must focus on shareholder profit, said Francois Vigneault, CEO of Seattle biotech Shape Therapeutics.
“The board is what gets in the way; they want to maximize the gain,” said Vigneault, whose company is privately held. “That’s just greed. That’s just an incentive that’s misaligned between the structure of corporate companies and what we should be doing that’s good for the world.”
Even when the market is treated, they may not stay there. The same year Orchard stopped investing in the Wiskott-Aldrich treatment, it also stopped distributing a drug called Strimvelis, which is approved in Europe to treat the rare disease ADA-SCID, or “bubble boy syndrome”.
‘A huge challenge’
Claire Booth, professor of gene therapy and pediatric immunology at University College London, is among those working for change. She co-founded Access to Gene Therapies for Rare Diseases, which brings together people across Europe representing academic groups, patient advocates, regulators, funders and drug makers. They hope to create an independent non-profit that can support market authorization and access to commercially unsustainable therapies.
A related US effort, The Bespoke Gene Therapy Consortium, was organized by the Foundation for the National Institutes of Health and includes the FDA, various NIH institutes, and several drug companies and nonprofits. The group’s goals include supporting a handful of clinical trials and exploring ways to streamline regulatory processes.
Some researchers are trying to tackle the problem scientifically. Dr. Anna Greka that the Broad Institute MIT and Harvard launched an effort to look at the commonalities behind the different conditions – or nodes, which can be compared to branches meeting at a tree trunk. Fixing the nodes with gene therapies or other treatments, rather than certain “misprints” in DNA responsible for a single disorder, could tackle multiple diseases at once.
“What this does is it increases the number of patients who can benefit from the therapy,” said Broad member Greka. “It also makes it much easier or more attractive for anybody, like a biopharmaceutical company, to take the project forward and try to get it to the clinic, because they’ll have a bigger market.”
In the meantime, affected families are partnering with each other and with scientists to help move the needle. Genethon was created by an association of patients and their relatives to develop treatments for a number of rare diseases. And the head of the foundation involved in Opus Genetics has a child with a rare genetic retinal disease.
There is also new hope for families dealing with Wiskott-Aldrich and bubble boy disease. Last year, the Telethon Foundation in Italy took responsibility for the production and distribution of Strimvelis. This year, the charity announced it had been selected for a European Medicines Agency pilot program that could help guide its Wiskott-Aldrich gene therapy through the regulatory process there.
Still, scientists say these efforts do not negate the larger financial quandary of rejecting the therapies for rare diseases, and it may take some time before such genetic treatments are available to patients worldwide. deep
“This is a huge challenge, and I’m not entirely sure we’re going to be able to overcome it,” Booth said. “But we have to try because we’ve spent years and millions doing these transformative treatments. And if we don’t try, it feels like the end of an era.”
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The Associated Press Health and Science Section is supported by the Howard Hughes Medical Institute Science and Media Education Group. The AP is solely responsible for all matters.
