The devastating neurodegenerative disease typically affects young boys and causes death within 10 years.

In a recent clinical trial, a gene therapy to treat cerebral adrenoleukodystrophy (CALD) effectively stabilized the disease's progression in 88 percent of patients, researchers from the Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Massachusetts General Hospital reported.

According to their results, published in the New England Journal of Medicine, 15 of 17 patients had stable neurologic functioning more than two years on average after receiving the gene therapy, which was administered in a clinical trial sponsored by bluebird bio. It is one of the largest gene therapy trials targeting a single-gene disease to be published to date.

"Although we need to continue to follow the patients to determine the long-term outcome of the gene therapy, so far it has effectively arrested the progress of cerebral adrenoleukodystrophy in these young boys," said David A. Williams, MD, chief scientific officer and senior vice-president for research at Boston Children's Hospital and president of Dana-Farber/Boston Children's Cancer and Blood Disorders Center and the lead author of the study. "This is a devastating disease, and we are all quite grateful that the patients and their families chose to participate in the trial."

The treatment leverages bluebird bio's proprietary Lenti-D gene therapy to deliver the functional gene to patients' stem cells in the laboratory. "The clinical experience with Lenti-D demonstrates the potential for gene therapy to benefit patients with CALD," said David Davidson, MD, chief medical officer of bluebird bio. "Early intervention is important to optimize outcomes, so the recent implementation of newborn screening in many states will improve the ability to provide timely treatment to preserve neurologic function in affected boys."

Bluebird bio is engaged in ongoing discussions with the FDA and European regulators on their plans to bring the therapy to market.

"This treatment results from more than two decades of investment in basic gene therapy research by the NIH and others," Williams said. "It really demonstrates that research funding is essential to developing the next generation of therapies for devastating childhood diseases."

"Since it was first described 100 years ago, adrenoleukodystrophy has robbed the function of children who, up until the disease's onset, had been developing normally," said Florian Eichler, MD, co-lead author on the study and the director of the Leukodystrophy Service at Massachusetts General Hospital. "These are children who have been growing and thriving, and then suddenly, their parents witness this devastating decline that starts with personality changes and then progresses to motor problems and loss of their ability to walk and talk."

Until now, stem cell transplantation using cells donated by another person has been the only known effective therapy for CALD. Yet, its efficacy is drastically reduced if performed during later stages of neurodegeneration and usually works best with a disease-free matched sibling donor, which fewer than one-quarter of CALD patients have.

To perform the gene therapy, clinicians first collect a patient's blood stem cells, which give rise to all mature blood cells. In a highly-specialized laboratory that contains a clean room for preparation of medicines, a viral vector is used to insert a correct version of the faulty gene into the patient's stem cells. Then, after the patient receives chemotherapy to make room for the genetically altered blood stem cells in the bone marrow, the cells are infused back into the patient's bloodstream via an intravenous line.

"In my clinic, the impact of this trial has been phenomenal," Eichler said. "Boys without a donor match for stem-cell transplant were often passing away within a year or two of their diagn