A new research effort takes aim at 8 rare diseases. It could revolutionize many more.
Terry Pirovolakis raised $4.5 million – $20 at a time – to help develop treatments for his son Michael's devastating rare disease.
Jocelyn Duff collected more than $1 million from friends and neighbors the first year after her daughter Talia was diagnosed with a terrible genetic condition.
Until now, that has been about the only option available to families afflicted with one of 7,000 rare, inherited, untreatable diseases: Watch your loved one suffer and possibly die – or do that while also trying to raise money to study the disease and potential therapies, educate yourself about medicine, genetics and drug development, raise other children, and somehow keep the family afloat mentally and financially.
But a new public-private collaboration aims to ease those challenges by creating a road map for advocates to follow while pursuing therapy. The project, called the Bespoke Gene Therapy Consortium, or BGTC, is intended make an arduous, emotional and time-consuming process at least a little clearer.
The consortium is starting with eight diseases, including the ones affecting Talia Duff and Michael Pirovolakis, whose parents' fundraising created enough data and momentum to make them good early candidates for the project.
"When will we stop this madness of funding rare disease research through bake sales and road races? That's what's at the heart of what BGTC has to offer," Duff said. "We need dozens and dozens of BGTCs."
Roughly 30 million Americans have a so-called rare disease, most of which are inscribed in a single gene patients have carried in every cell since before birth. Tinkering with those genes, which is only just becoming medically possible, offers a path – first to a treatment and later, hopefully, to a cure.
Each disease is distinct, affecting different genes and in different ways, so each treatment has to be developed individually, typically after years or decades of effort.
The Bespoke Gene Therapy Consortium plans to develop gene therapies for each of the eight carefully chosen diseases over the next year, begin clinical trials late next year, and see results 12 to 18 months after that.
Just getting selected to participate in the Bespoke Gene Therapy Consortium was a major hurdle. The eight diseases, including Talia's Charcot-Marie-Tooth disease type 4J or CMT4J, which causes progressive muscle weakness, were selected as treatment candidates because they had a good chance of being quickly successful.
Now 17, Talia wears a tube to help her breathe, uses a wheelchair and has no use of her arms. She has just a little muscle strength remaining in her left hand and right leg. She was misdiagnosed and incorrectly treated for six years before advances in gene testing revealed the true cause of her declining physical control.
Her disease does not affect her intellect or personality.
"Talia is still her sassy, smart, funny, vibrant self," Duff said a few days after her daughter's junior prom. "She's the kind of kiddo that after you have a conversation with her, when you leave the room, somehow you feel changed. She's just so resilient and she just focuses on right now, what's in front of her."
Talia's friend helped start a 3-mile road race and fundraiser, an annual "chase the butterfly" event, that has been widely supported by their home community of Ipswich, Massachusetts, population 13,000. Family and friends raised $1 million for CMT4J research within a year of Talia's diagnosis.
But the work is exhausting and endless, not to mention unrealistic for most families who live in less advantaged communities or who can't afford to have a parent quit work to lead the charge.
The consortium, led by the Foundation for the National Institutes of Health, a nonprofit wing of the federal agency, has helped raise $97 million to advance the treatments. In addition to arms of the NIH, other partners include the Food and Drug Administration, biopharmaceutical and life science companies, nonprofits and the state taxpayer-supported California Institute for Regenerative Medicine. Consortium meetings have involved as many as 175 people from various institutions.
The work is particularly urgent now, because funding in the biotechnology industry has dried up since the early days of the coronavirus pandemic, and many companies, including one started work on CMT4J, have stopped pursuing treatments for rare diseases.
"It's a symptom of the overall situation that small biotech companies are facing right now," said Dr. Julie Gerberding, president and CEO of the Foundation for the NIH, citing "investor uncertainty and investors not wanting to put money into enterprises where there's high risk and increasing fear that ultimately, the overall commercial model won't support their return on investment."
The aim of the consortium is to ease the risks of that investment by providing early clinical trials showing the gene therapies are safe and effective, she said.
Although starting small, the consortium could lay the groundwork for many other diseases and approaches later on, said Dr. Jeremy Levin, chairman and CEO of Ovid Therapeutics Inc., a biotech aimed at rare neurological conditions.
"You are creating something that's important – not just for that child, not just for that disorder, for the 100 to 200 people, but you're laying down tracks for understanding what five, 10, 15, 20 years from now may be the norm for all therapeutics," Levin said, such as treatments for cancer, Parkinson's, epilepsy and some psychiatric conditions, as well as rare diseases. This project will help define patient safety, manufacturing processes and clinical trial protocols for those future treatments, he said.
To be selected for the program, a disease had to have an identified and correctable genetic mutation, an animal model that could be treated first to ensure safety, and a way to measure treatment success in 12 to 18 months, among other attributes, said Courtney Silverthorn, an associate vice president of the foundation. More than 60 advocacy groups applied to the program in December 2021, with the selection of the final eight announced Tuesday. About 2,200 Americans, most of them children, have been diagnosed with one of these eight diseases.
They are:
Charcot-Marie-Tooth disease type 4J (CMT4J).
Congenital Hereditary Endothelial Dystrophy.
Morquio A Syndrome.
Multiple Sulfatase Deficiency.
NPHP5 Retinal Degeneration.
Propionic Acidemia (PCCB).
Retinitis pigmentosa 45.
Spastic paraplegia 50 (SPG50).
Some, like Talia's CMT4J and Michael's SPG50, involve the brain, and treatment will be delivered to the spinal cord. Other gene therapies address eye diseases and can be given in low doses directly to the eye; more need to be given systemically to the whole body.
Clinical trials could start late next year and will include 65 to 75 patients, sometimes nearly all of the patients with the ultra-rare disease.
But that's just the starting point.
"It's really about using those clinical trials to validate protocols that can then be used for any other gene therapy for rare disease," Silverthorn said.
All five of the eligible American children with spastic paraplegia 50, a slowly progressing neurodegenerative disorder, will be included in the trials. The disease often includes epilepsy and small brain size. Most children with SPG50 lose use of their arms by age 10 and their legs by 20. There's no evidence of people with it living past 30.
Pirovolakis quit his job as an information technology executive to start a company so he could speed development of treatments for SPG50 and other rare diseases. Michael received his gene therapy a year ago.
The BGTC program takes "the burden off these families to focus on what they need to focus on, which is their sick children," Pirovolakis said. "Once you've proven that the gene therapy will work … you can make a template for that."
Pirovolakis and Duff have to face the reality that all of their hard work won't save their own children. Although it's hoped gene therapy can provide a one-time cure for a newborn or child, once a neurological condition has taken hold – sometimes even before birth – the best parents can hope for is to slow or stop their child's decline.
It's heartbreaking, Duff said, to look back at pictures of Talia from a few years ago – like one in which she's leaning over a microscope, her arms resting on a lab bench – and realize what might have been if she could have received treatment then and her disease progression had been stopped.
"The toolbox we have today just isn't good enough to cure our kids," Pirovolakis said. "We're five years too early to save the kids completely. But at the same time, we have to do something now for these kids. We can't forget this generation."
Contact Karen Weintraub at kweintraub@usatoday.com.
Health and patient safety coverage 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 input.
This article originally appeared on USA TODAY: New gene therapy consortium seeks to accelerate rare disease research
