NIH-funded research supports early screening of and treatment for rare brain disorder
Findings of the first study examining long-term outcomes of a treatment for Krabbe disease suggest the intervention is most effective when done before symptoms appear and may help children live at least into their early teen years. Krabbe disease is a devastating brain disorder that primarily affects children and can be fatal at a young age. The study, published in Neurology, received support from the NIH’s National Institute of Neurological Disorders and Stroke (NINDS).
“Long-term studies can give patients and their families some answers when they may be facing countless questions and the research can also provide invaluable information to scientists who are working on treatments,” said Jill Morris, Ph.D., program director at NINDS. “With risk of Krabbe being identified by newborn screening this study may justify treating patients with less severe symptoms to prevent further decline and to dramatically increase their life expectancy.”
A group led by Maria L. Escolar, M.D., director of the Program for the Study of Neurodevelopment in Rare Disorders at the University of Pittsburgh School of Medicine, examined long-term outcomes in 18 children who received hematopoietic stem cell transplantation (HSCT) before they were seven weeks old. Children selected for this study were at high risk for developing early-onset Krabbe disease based on family history or newborn genetic screening.
In 2005, Dr. Escolar’s team discovered that HSCT for Krabbe disease was associated with benefits that lasted for at least three years but current study followed the children for up to 15 years. The study involved comprehensive annual evaluations of cognitive, speech and motor function; tests of the speed and strength of electrical signals from peripheral nerves; and responses by visual and auditory systems. The children also participated in brain imaging.
The findings indicated that early treatment was associated with improved quality of life and longer lifespans compared to untreated children or children who received HSCT after 6 weeks of age.
The majority of the 18 children in the study continued to improve their motor, cognitive and language skills, which typically degrade as the disease progresses. Ten of the 18 children can now walk, two independently and the rest with assistive devices. Five children died over the course of the study: one from disease progression 15 years later, one of unrelated causes and three from transplant complications.
“Our study provides evidence that the youngest babies who are at risk of developing the most severe form of Krabbe disease should be strongly considered for HSCT as soon as possible,” said Dr. Escolar. “HSCT, like all surgical procedures, does carry some risks, so parents may be inclined to wait until Krabbe symptoms develop, but our findings suggest that may be too late for the best outcomes.”
Krabbe disease is a rare disorder that occurs when there is a lack of the protein galactocerebrosidase (GALC), which helps clear unneeded molecules out of cells. If there is not enough GALC, molecules and proteins accumulate in cells, which causes them to function abnormally. The disease progresses quickly in children diagnosed at a young age and results in seizures, muscle weakness, blindness and problems with thinking and memory. Many of these children will not live past age 2. Krabbe disease is often diagnosed in infants younger than 6 months of age but some less severe forms of the disease appear later in life, including in adulthood.
Hematopoietic stem cell transplantation (HSCT) is currently the only treatment for Krabbe disease. In this procedure, infants receive umbilical cord blood, which then travels around their body providing the missing GALC protein. HSCT has been shown to slow progression of the disease, but does not cure it.
Dr. Escolar and her colleagues will continue to monitor the children to see if any symptoms of the disease develop or worsen. In addition, they plan to focus on finding treatments for peripheral nerve disease, which is associated with later stages of Krabbe, causing severe muscle weakness.
This study received support from NINDS (NS061965).
For more information:
Krabbe Disease Information Page
References:
Wright MD. Developmental outcomes of cord blood transplantation for Krabbe disease: A fifteen year study. Neurology. August 30, 2017.
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The NINDS (http://www.ninds.nih.gov) is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.