The promise of gene therapy is great for families dealing with rare genetic diseases. Such treatments offer the possibility of unique cures.
But families and researchers worry that such therapies remain out of reach.
Collectively, around 350 million people worldwide suffer from rare diseases, the majority of which are genetic. But each of the 7,000 individual diseases affects perhaps a few in a million people or fewer. Therefore, there is little commercial incentive to develop or bring to market these unique therapies to correct defective genes or replace them with healthy genes.
The Associated Press examined what this means for families, scientists and the nascent field of gene therapy.
Here are the key takeaways from AP Report.
Families are frustrated and some are trying to raise their own funds.
Camden Alderman was diagnosed as a baby with a rare disease called Wiskott-Aldrich syndrome, which is caused by a gene mutation on the X chromosome. It mainly affects boys – up to 10 in every million – and can cause frequent infections, eczema and excessive bleeding.
When he was a child, doctors removed his spleen because of uncontrolled bleeding. As a boy, he ended up in the hospital many times and was told he couldn’t play baseball.
His mother, Robin Alderman, remembers a doctor saying, “Basically, your son’s only chance of a cure will be gene therapy.”
He also told her that researchers were not accepting U.S. residents into a clinical trial for the treatment, which “broke my heart,” she said. There is still no clinical trial he can participate in, and London-based Orchard Therapeutics has stopped investing in an experimental treatment for the disease in 2022.
Lacey Henderson’s 5-year-old daughter Estella has childhood alternating hemiplegia, a neurological condition that affects 300 people in the US. Estella has cognitive delay, has limited use of her hands and suffers episodes that temporarily paralyze part or all of her body, Henderson said. Medications can reduce symptoms, but there is no cure.
His family in Iowa raises money through GoFundMe and a website to develop a gene therapy. They raised about $200,000.
“We have three different projects with various researchers,” Henderson said. “But the problem is that everything is underfunded.”
Financial disincentives can harm the process.
The amount of work required to move from 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 recent years, he said, investment in gene therapy has largely declined.
“If you have to spend $20 million or $30 million to get approval and you have five or 10 patients a year, it’s going to be difficult to get a return on your investment,” Kohn said. “So we have safe and successful therapies, but it’s more the financial and economic elements that limit them from becoming approved medicines.”
Ultimately, most biotech companies go public and must focus on shareholder profits, said François Vigneault, CEO of Seattle biotech company Shape Therapeutics.
“The board is what gets in the way; they’re trying to maximize the gain,” said Vigneault, whose company is privately held. “This is just greed. This is just a misaligned incentive between the corporate structure of the company and what we should be doing that is good for the world.”
Scientists, nonprofit organizations and patient groups are working toward solutions.
In the US, for example, the Bespoke Gene Therapy Consortium was organized by the Foundation for the National Institutes of Health and includes the FDA, several NIH institutes, and several pharmaceutical companies and non-profit organizations. Its goals include supporting multiple clinical trials and streamlining regulatory processes.
Researchers are trying to solve the problem scientifically. Anna Greka said the Broad Institute of MIT and Harvard has launched an effort to look at the commonalities behind various conditions — or knots, which can be compared to branches that meet on the trunk of a tree. Correcting the nodules with gene therapies or other treatments, rather than specific “spelling errors” in the DNA responsible for a disease, could potentially resolve multiple diseases simultaneously.
“What this does is increase the number of patients who can benefit from therapy,” said Broad Fellow Greka.
Still, scientists say these efforts do not negate the larger financial dilemma surrounding therapies for rare diseases, and it may be some time before such gene therapies are available to patients around the world.
“This is a huge challenge and I’m not sure we’ll be able to overcome it,” said Claire Booth of University College London. “But we have to try because we have spent decades and millions making 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 Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. AP is solely responsible for all content.
