Gene therapy may help seniors at NC A&T State University lead ‘an easier life’

GREENSBORO, NC — Robin Alderman faces a painful reality: gene therapy can cure her son Camden’s rare inherited 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 join.

“We feel like we’re the forgotten ones,” said Alderman, who has been an advocate for her 21-year-old son since he was a baby.

Altogether, 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 is little commercial incentive to develop or bring to market these one-off therapies to fix faulty genes or replace them with healthy ones. That leaves families like the Aldermans scrambling for help and some scrambling to raise money on their own for cures that may never come.

“These children have been doubly unfortunate: A, because they got a genetic disease, and B, because the disease is so rare that no one 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 hinder progress in the nascent field of gene therapy, erasing the potential for 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 major Italian charity announced in February that it is taking over the Wiskott-Aldrich treatment that Orchard had followed. And an arm of the charity 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 been selling bread. One family has mortgaged their house to give some money to research into their rare disease,” Bennett said. “I just feel responsible to help them.”

The pain of families

Aldermen 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 mainly affects boys – up to 10 in every million – and can cause frequent infections, eczema and excessive bleeding.

When he was little, doctors removed his spleen because of uncontrolled bleeding. As a young man, he was injured in the hospital many times and was told he could not play baseball.

One treatment is a bone marrow transplant. But he is black and of Korean heritage, making it difficult to find a donor – people are more likely to match someone with a similar ancestral or ethnic background. Robin Alderman recalls one doctor saying, “Basically, your son’s only chance for a cure is going to be gene therapy.”

He also told her that her researchers were not then accepting US residents in a clinical trial, which “just broke my heart,” she said.

Today, Camden Alderman is a rising student at North Carolina Agricultural and Technical State University. He takes penicillin daily and gives himself weekly infusions of immunoglobulin under the skin, which help fight the 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 cure, he said, “it would just help me lead an easier life.”

This has been proven for patients who underwent experimental therapy, such as the 14-year-old son of Dr. Priya Stephen, who participated in a clinical trial in Italy that accepted Americans at the time.

While Stephen is grateful, she said, she can’t help but feel guilty that her family had an opportunity that others don’t: “It’s just ethically unacceptable to have a treatment that we know works, that we know that it is safe, that people all of a sudden can not enter.”

For a while, it seemed that gene therapy for Wiskott-Aldrich was 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 transferred another therapy to Orchard, which announced in 2019 that it had secured a designation from the US Food and Drug Administration intended to expedite development and review. But Orchard stopped investing in this and two other rare disease treatments a few years ago, with CEO Dr. Bobby Gaspar who said the company sympathized with the affected families and would look for other ways to advance therapies.

“There are a large number of diseases out there that could benefit from gene therapy, but for which there is no benefit 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 has not passed the early stages for many of them.

Lacey Henderson’s daughter, Estella, 5, has childhood alternating hemiplegia, a neurological condition that affects 300 people in the U.S. Estella is cognitively delayed, has limited use of her hands, and is temporarily paralyzed on part or all of her body. her. Henderson said. Medications can curb symptoms, but there is no cure.

Her family in Iowa is raising funds through a GoFundMe and a website to develop a 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 unfunded.”

‘wrong’ incentives

Scientists say financial disincentives hinder the process, from drug discovery to development.

The amount of work to move from a lab 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.

In the past two years, he said, investments in gene therapy have 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 and safe therapies, but it’s more the financial and economic elements that are limiting them from turning into approved drugs.”

At the end of the day, most biotech companies go public and need to focus on profiting shareholders, said Francois Vigneault, CEO of Seattle biotech Shape Therapeutics.

“The board is the thing that gets in the way; they’re trying to maximize profit,” said Vigneault, whose company is held privately. “That’s just greed. That’s just a misalignment between the corporate company structure and what we need to do that’s good for the world.”

Even when treatments hit the market, they may not stay there. In the same year, Orchard stopped investing in the Wiskott-Aldrich treatment, it also stopped distributing a drug called Strimvelis, approved in Europe to treat the rare disease ADA-SCID, or “bubble boy syndrome.”

‘massive 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 Disease, which brings together people across Europe representing academic groups, patient advocates, regulators, funders and drug manufacturers. They hope to create an independent non-profit organization that can support market authorization and access to therapies that are not commercially viable.

A related effort in the US, 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 variety of clinical trials and exploring ways to improve regulatory processes.

Some researchers are trying to tackle the problem scientifically. Dr. Anna Greka said the Broad Institute of MIT and Harvard has launched an effort to look at the commonalities behind different conditions – or nodes, which can be compared to branches meeting in a tree trunk. Fixing the nodules with gene therapy or other treatments, rather than the specific “spelling mistakes” in the DNA responsible for a disorder, can treat multiple diseases at once.

“What this does is it increases the number of patients who can benefit from the therapy,” said Greka, a Broad Fellow. “It also makes it infinitely 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’re going to have a bigger market.”

Meanwhile, affected families are collaborating with each other and scientists to help move the needle. Genethon was created by an association of patients and their relatives to develop treatments for several rare diseases. And a foundation executive involved in Opus Genetics has a child with a rare genetic retinal disease.

There is also new hope for families dealing with Wiskott-Aldrich disease and blisters. Last year, the Telethon Foundation in Italy took over 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 the Wiskott-Aldrich gene therapy through the regulatory process there.

However, scientists say these efforts do not negate the larger financial problem surrounding therapies for rare diseases, and it may be some time before such genetic treatments are available to patients worldwide.

“This is a massive challenge and I’m not entirely sure we’ll be able to overcome it,” Booth said. “But we have to give it a go because we’ve spent decades and millions doing these transformative treatments. And if we don’t try it, then it feels like the end of an era.”

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science Media and Education Group. AP is solely responsible for all content.