What you need to know about the forces reshaping our industry.


October 9, 2017

A medical first: Small gene therapy trial successfully halts fatal brain disease in children

Daily Briefing

    Researchers for the first time have successfully used gene therapy to halt a deadly degenerative brain disease for more than two years of follow up, according to a new study in the New England Journal of Medicine.

    Learn 9 steps your organization can take on the path toward personalized medicine


    The study assessed the results of an early trial for Bluebird Bio's Lenti-D (elivaldogene tavalentivec) therapy as a treatment for cerebral adrenoleukodystrophy (cALD), a disease that kills nerve cells in the brain and typically results in death within five years of diagnosis. According to the New York Times, the disease affects about one in every 20,000 boys, with the symptoms typically presenting at about age 7.

    The sole treatment for the disease was a bone-marrow transplant, either via a compatible donor or via cord blood, provided cord blood was saved at birth. However, the transplant process is dangerous, with a mortality rate as high as 20 percent and the risk of permanent disabilities among those who survive, the Times reports.

    A new form of treatment with promising results

    But according to the new study, gene therapy may provide a new treatment for the disease. The researchers found that the therapy can halt the disease's progression without side effects, so long as the treatment is provided early on when the only signs of deterioration are changes in brain scans, according to the Times.

    For the study—led by David Williams, the chief scientific officer at Boston Children's Hospital—17 boys ages 4 to 13 who had the disease were given the gene therapy. The therapy involved collecting stem cells from the study participants' bone marrow, tweaking the cells with the Lenti-D vector, and then reinfusing the cells into the patients.

    According to the Times, the process relies on using a disabled form of HIV to insert a normal form of the ALD gene into a human cell. HIV is a better option than other viral carriers, the Times reports, because it is able to deliver genes into human cells more safely than comparable alternatives.

    After having the altered stem cells reinfused into their systems, participants have to wait about a year while the cells multiply and slowly drift to the brain, where they convert into glial cells, or the cells that surround and help insulate neurons. At that point, the proper gene in the glial cells kicks in, halting brain deterioration stemming from the disease. However, that year-long delay between treatment and results means that the therapy has to be delivered before symptoms begin to appear, since patients with symptoms will likely deteriorate before the reinfused stem cells can work effectively, the Times reports.

    The study found that after two years, 15 of the 17 children involved were functioning normally without obvious symptoms, and all of them were producing functional ALD protein. The remaining two participants died, one because his disease progressed too rapidly. The other passed away after dropping out of the study to undergo a bone-marrow transplant and suffering complications from the procedure.

    Next steps

    The study represents one of the largest gene therapy trials aimed at a single-gene disease that has been published, and Bluebird has received regulatory approval to add additional participants, FierceBiotech reports.

    According to the Times, Bluebird has added eight participants to the trial. In a separate study, the company is comparing children who underwent bone marrow transplants with those who opted for gene therapy. All children enrolled so far have been given the option to participate for 13 years to monitor their condition.


    David Davidson, CMO at Bluebird, praised the results of the study and its implications. "The founding of Bluebird Bio was based in large part on the potential for Lenti-D to benefit boys with cALD," he said. "It is encouraging to see patients doing clinically well more than three years following treatment for this rare and devastating disease."

    Separately, Theodore Friedmann, a gene therapy researcher at the University of California-San Diego School of Medicine, said the study opens up new ways of using gene therapy to treat neurological diseases. "Many think the central nervous system is intractable and unapproachable," but this study proves them wrong, he said (Kolata, New York Times, 10/5; Taylor, FierceBiotech, 10/5).

    Next: 9 steps you can take on the path toward personalized medicine

    After years of anticipation, clinical innovations will make personalized medicine widely available. However, to realize its promise, providers will need to integrate clinical innovations with care delivery redesign.

    From risk assessment to shared decision-making to self-management, learn the nine steps your organization can take on the path toward personalized medicine.

    Download the Infographic

    Have a Question?


    Ask our experts a question on any topic in health care by visiting our member portal, AskAdvisory.