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Tuesday, October 10, 2017

Stem Cell Therapy Improves Function, Extends Survival in Children with Krabbe Disease

BY SARAH OWENS

Hematopoietic stem cell transplantation (HSCT) in the first seven weeks of life extended survival and improved function in asymptomatic children with early-infantile Krabbe disease for more than 15 years of follow-up, according to a study published online on August 30 in Neurology.

Caused by a deficiency in the enzyme galactocerebrosidase (GALC) that impairs the growth of myelin, Krabbe disease usually appears in early infancy and causes progressive muscle weakness, stiffness, and slowed mental and physical development. Umbilical cord blood transplantation can improve neurologic outcomes in the short term if performed before symptoms appear, but long-term outcomes are unknown.

The findings demonstrate that "HSCT performed before the onset of severe symptoms delays disease progression and improves both length and quality of life" over the long term, the study authors, led by Matthew D. Wright, MD, of the program for the study of neurodevelopment in rare disorders at the University of Pittsburgh in Pittsburgh, PA, wrote.

The study authors said that infants with a moderate to high risk of Krabbe disease "should be referred to specialized centers for evaluation since clinical expertise is needed to recognize the subtle signs of disease [and to] provide optimal counseling." Counseling could include the potential of of HSCT, to "achieve the best possible outcomes," they said.

For the study, researchers at the Children's Hospital of Pittsburgh enrolled 18 infants who had been diagnosed with early-infantile Krabbe disease through standard newborn screening or prenatal/neonatal diagnosis and who had undergone HSCT within the first seven weeks of life between October 1999 and October 2011. Of these, 15 completed follow-up testing.

At a baseline exam and at follow-up exams over four to 15 years of follow-up (average follow-up: 9.5 years), the researchers performed magnetic resonance imaging (MRI) and measured cerebrospinal fluid protein, as well as other motor, language, cognitive, and adaptive skill assessments.

Thirteen patients are still alive. Among surviving children, cognitive testing showed that one child has developed normally; ten surviving children continue to develop skills at a slightly lower rate compared to normally developing children; and two children's skills plateaued below the developmental age of two years.

Additionally, ten children continue to receive speech therapy; of these, two children require augmentative communication devices. While gross motor development was found to vary widely among the children, three patients are able to walk independently, and seven can walk with assistive devices. The children have spasticity ranging from very mild to severe, but they generally preserved their fine motor skills and can use their hands and fingers.

Finally, on MRI scans, the researchers found that brain myelination and atrophy stabilized in eight patients, improved in four patients, and worsened in one patient over the follow-up period. Nerve conduction velocities initially improved, but remain abnormal in most of the children.

The researchers noted two limitations to their study: Only children with the most severe form of Krabbe disease were enrolled, so the findings may represent only the worst outcomes of the disease; and more extensive follow-up studies are needed to confirm the findings.

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