Pediatric Blood and Marrow Transplant Program and University of Minnesota Masonic Children’s Hospital

The Pediatric Blood and Marrow Transplant Program at University of Minnesota Masonic Children’s Hospital has unsurpassed world-wide experience treating inherited metabolic storage diseases, including adrenoleukodystrophy (ALD). To date, we have treated more than 140 ALD patients with hematopoietic cell transplant (HCT), commonly known as blood or marrow transplant (BMT).

ALD is an inherited disorder that most severely affects males. It is caused by an abnormality in a specific gene on the X-chromosome. In ALD, the body fails to produce a protein that helps break down very long chain fatty acids. These very long chain fatty acids build up in the brain and adrenal glands. In about 40 percent of males with ALD, this build up causes rapidly progressing inflammatory changes in the brain during childhood. This is the “childhood-onset cerebral form” of ALD. In this form, changes in the brain usually begin between 4 to 8 years old. Some males, however, don’t develop brain changes until adulthood or may never get cerebral ALD. Currently, it is not possible to predict which males with ALD will develop cerebral disease. It is also not possible to predict when cerebral disease will happen.

As the disease advances, the first symptoms of cerebral ALD may be changes in behavior and in school performance. This is usually followed by problems with vision, hearing, coordination, memory, information processing, seizures and other neurologic problems. Without treatment, boys with the cerebral form of ALD usually die within a few years of the onset of symptoms. For that reason, early detection and treatment are critical.

When a child receives a diagnosis of ALD and changes in the brain begin to occur, a transplant should be considered as soon as possible. Ideally, the transplant is performed before symptoms from cerebral disease develop. If the symptoms from cerebral disease are severe, transplant may no longer be helpful in ALD. While HCT is the only treatment known to stop the progression of cerebral ALD, the use of gene therapy is currently being studied.

We transplanted our first patient with ALD in 1991. The goal of HCT is to stabilize the disease by preventing further loss of myelin. If HCT is successful, it can minimize further damage to the brain and nervous system. In 2015, our longest living ALD patient was 24 years post-transplant.

In 2005, University of Minnesota researchers successfully pioneered the use of the drug N-acetylcysteine in patients with advanced cerebral ALD. The drug therapy shows evidence of slowing the rapid progression of the disease in these patients as they go through transplantation. In addition, we continue to study transplant modifications and other therapies for patients with neurologically advanced cases of ALD. Our aim is to provide these patients with longer, higher-quality lives.

Our ALD program is led by Paul Orchard, M.D., Medical Director of the Inherited Metabolic and Storage Disease (IMSD) Program. Weston Miller, M.D., and Troy Lund, MD, PhD, partner with Dr. Orchard on the IMSD team, focusing on research as well as patient care. All three physicians are internationally recognized for their expertise and innovative approach to treating patients with ALD.

The ALD program at University of Minnesota Masonic Children’s Hospital includes expert health care providers who specialize in ALD within the areas of endocrinology, genetics, neurology, neuropsychology, neuroradiology, and physical and occupational therapy. This multidisciplinary team approach ensures that the care we provide best meets the unique needs of each patient and family.

Researchers at the University of Minnesota continue to explore innovative ways to increase treatment success for patients with ALD. Our scientists lead the field in several areas of IMSD research and in translating their findings into clinical practice.

Research projects being explored include:

• minimizing transplant related complications
• use of reduced intensity preparative regimens to make transplant safer for patients with early and advanced ALD
• risk factors affecting outcomes following transplantation
• basic biology of metabolic storage diseases and the implications for patients
• immune reconstitution to monitor the risk of infection after HCT
• late effects of bone marrow transplantation
• testing for markers of disease activity
• use of gene therapy to treat childhood cerebral ALD
• use of HCT to treat adults males with cerebral ALD
• use of intrathecal mesenchymal stem cells to treat patients with advanced cerebral ALD who are not transplant candidates
• use of very high cell-dose umbilical cord blood transplantation to improve outcomes following transplant for cerebral ALD (contact us for more information)