Groundbreaking gene therapy for adrenoleukodystrophy (ALD) approved and available at M Health Fairview Masonic Children’s Hospital
A team of dedicated physicians and researchers at M Health Fairview Masonic Children’s Hospital helped pioneer a gene therapy for treatment of cerebral adrenoleukodystrophy (ALD), a rare genetic, neurodegenerative disease that primarily affects boys.
Recently approved by the U.S. Food and Drug Administration (FDA), the new gene therapy replaces the defective gene that causes ALD, called ABCD1, with a functioning copy.
As a global leader in ALD care, our hospital was a prominent site in clinical trials and is now one of only a handful of centers in the world offering gene therapy to treat cerebral ALD.
“The transplantation of blood stem cells from a healthy donor has been used for decades to treat cerebral ALD,” said Paul Orchard, MD, pediatric blood and marrow transplant physician at Masonic Children’s Hospital. “While effective, these transplants are associated with significant risks, including a mortality rate between 10 and 20 percent. Having another option for these patients – one that uses their own blood stem cells engineered with a functional copy of the ABCD1 gene – may prove significantly safer than using a donor.”
The devastation of ALD
ALD affects one in 17,000 people by disrupting the body’s natural ability to break down very long chain fatty acids, which then build up in blood and tissues, including the brain. The buildup of these fatty acids damages and can eventually destroy myelin, the protective sheath around nervous system cells.
Cerebral ALD is the most severe form. It progresses quickly and leads to loss of neurological function, including the ability to speak, walk, see, and hear. Left untreated, patients with cerebral ALD typically don’t make it through their first decade.
Boys are at higher risk of developing ALD because the gene defect is on the X chromosome. Since females are born with two X chromosomes, they have access to a second, healthy copy of the ABCD1 gene. Boys, however, have only one X chromosome and therefore cannot decrease the severity of the disease with a second functional gene.
Prior to FDA approval of gene therapy, the only approved treatment to halt the disease’s progression was bone marrow or umbilical cord blood transplant. Transplantations have limitations and risks, and gene therapy may be a safer and more efficient opportunity.
How gene therapy works
Gene therapy for cerebral ALD involves removing some of a patient’s defective blood stem cells, correcting the problem within the cells, and putting them back into the body – where they replicate and eventually replace other defective cells.
First, our pediatric hematology team collects blood cells from the patient by a process called apheresis, which mobilizes the stem cells from their location in the bone marrow into the blood where they can be harvested.
These blood stem cells are then purified and sent for manufacturing, which uses a virus designed to transfer a healthy copy of the ALD gene (ABCD1) into the cells. The cells are frozen while testing is performed to ensure the gene transfer process was successful and are sent back to the hospital.
Before the corrected cells can be infused back into the patient, the patient must undergo chemotherapy to eliminate the blood-producing cells that have an abnormal copy of the ABCD1 gene. Following this, the corrected cells are infused into the patient through an IV. Once in the body, the cells reproduce and take the place of the previous, defective cells.
Early detection of the disease is crucial for successful treatment. ALD can be diagnosed by an MRI scan of the brain. Pediatric patients with ALD are eligible for this new therapy if their brain hasn’t yet been critically damaged by the disease.
