A New Hope for Fanconi Anemia: Antibody Therapy Offers safer Path to Transplant
Fanconi anemia (FA) is a rare, inherited disorder that progressively damages bone marrow, leading to serious health problems including anemia, birth defects, and a dramatically increased risk of cancer. Typically diagnosed in early childhood, FA often manifests with physical abnormalities and a susceptibility to bleeding. Without treatment, approximately 80% of individuals with FA experience progressive bone marrow failure by age 12, a condition that can be fatal.
However, the standard treatment – a stem cell transplant – presents a tough paradox. While transplants can halt bone marrow failure, the necessary preparatory chemotherapy and radiation carry significant risks, frequently enough leading to secondary cancers. Currently, nearly all FA patients develop cancer by the time they reach their 40s. Now, researchers at Stanford University are pioneering a new antibody-based approach aimed at drastically reducing this risk.
Early Trial Shows Remarkable success
A recent clinical trial involving three young patients, all under the age of 10 and with varying genetic forms of FA, has yielded incredibly promising results. each child received a single intravenous dose of a novel antibody, briquilimab, 12 days prior to receiving a stem cell transplant from a parent. Crucially, the transplant protocol excluded the customary, toxic conditioning regimen of busulfan, chemotherapy, and radiation. the donated stem cells were also carefully processed to remove possibly harmful immune cells.
Within two weeks of the transplant,the new stem cells successfully engrafted in the patients’ bone marrow. Remarkably, none experienced graft rejection. By one month post-transplant, donor cells had nearly completely replaced the patients’ own, achieving a level of donor cell presence – known as chimerism – far exceeding initial expectations. The research team had initially hoped for just 1% donor cell presence; two years later,all three children have reached nearly 100% chimerism.
“We’ve been surprised by how well it’s worked,” said researcher Dr. Czechowicz. “We were optimistic that we would get here, but you never know when you’re trying a new regimen.”
A Brighter Future for Patients and Families
While transplants remain a challenging process, the new protocol significantly reduces toxicity.Ryder, one of the trial participants, spent over a month in the hospital and experienced temporary side effects like exhaustion, nausea, and hair loss. His mother,reiley,expressed relief that these hardships were temporary. “It was heartbreaking to see him go through things like that – I’d rather go through it than my child,” she said. ”I felt the heartbreak for him, and now he doesn’t have to.”
Since his recovery,Ryder has experienced significant improvements in his health,including increased growth,weight gain,and a reduction in frequent illnesses. Reiley emphasizes the importance of Ryder’s contribution to the research.”I think he takes a lot of pride in that, too,” she said, knowing his experience will help others facing the same diagnosis.
Expanding the Reach of the New Therapy
Dr.Agarwal, a leading researcher on the team, is keen about offering families a less toxic treatment option after over three decades of relying on traditional methods. “When I counsel families, their eyes start to shine as they think, ‘OK, we can avoid the radiation and chemo toxicity’,” she explained.
stanford’s team is now conducting a phase 2 clinical trial to evaluate the antibody approach in a larger group of children with FA. they are also investigating its potential request to other rare bone marrow failure disorders, such as Diamond-Blackfan anemia. Moreover, researchers are exploring weather the antibody can benefit elderly cancer patients who are unable to tolerate the intensity of conventional conditioning regimens.
“That population is frequently enough at a disadvantage,” dr. Agarwal noted. “It may provide us with a way to treat them with less intensity so it’s possible for them to get a transplant.” The team is also actively developing next-generation antibody-based treatments to further refine and improve outcomes for FA and related diseases.
A Collaborative Effort
This groundbreaking research is the result of a collaborative effort involving researchers from Stanford University, the University of California, San francisco, Kaiser Permanente Bernard J. Tyson School of Medicine, St. Jude Children’s Research Hospital, Memorial Sloan Kettering Cancer Center, and Jasper Therapeutics Inc.The study was supported by funding from anonymous donors, the california Institute of Regenerative Medicine, and the Fanconi Cancer foundation, with briquilimab provided by Jasper Therapeutics and logistical support from the Stanford Clinical Trial Program.
