HJKRI – Clinical Research

Krabbe World Wide Registry (WWR)

From the inception of Hunter’s Hope in 1997, the Foundation has gathered medical information from families affected by Krabbe Disease. In 2008, this registry officially became the Krabbe World Wide Registry and is now the center of all clinical research at the HJKRI. Currently, the WWR contains the medical records of more than 150 patients, making this registry the largest of its kind. The WWR provides invaluable information into diagnosis, outcomes, symptom management and treatment of Krabbe Disease.

Parent questionnaires and medical records are accessed and reviewed with a focus on clinical signs and symptoms, disease course, family history and results of biochemical, genetic and neurodiagnostic studies. In order to increase the number of patients with a known genotype, mutation analysis is performed on saliva and newborn blood spots. Results are then compared with clinical course to provide genotype/phenotype correlations. In addition, MRI discs from affected patients are reviewed in an effort to correlate neuroradiologic findings with phenotype and disease course.

This important registry is solely dependent upon family participation. If you are a family affected by Krabbe Disease and are not yet enrolled in the WWR, we urge you to contact the Hunter’s Hope Family Program Representative, Kathleen Scott, as soon as possible.

Once you connect with the Family Program Representative, you can expect to receive a packet from the Hunter’s Hope Research Team.  After answering some questions about your child, simply send  the packet back to the Research Team.  As the team members and the Clinical Director of the HJKRI review the information provided, you may be contacted by the Clinical Care and Research Coordinator for additional medical records or specialist’s contact information.

By enrolling your child in the WWR, you are providing invaluable information that makes advancements toward better treatments and ultimately a cure for Krabbe and other Leukodystrophies.

Clinical Research Activity

All clinical research through the HJKRI is built around the information contained in the WWR. The following projects are providing a more in-depth understanding of the genotype/phenotype correlation, or the long-term outcomes for the various types of Krabbe Disease. The team at the HJKRI works closely with experts across the country to accomplish this goal.

Krabbe Newborn Screening Consortium

The Krabbe Consortium began in 2006 when New York became the first state to screen for Krabbe Disease. The Consortium, a multidisciplinary group of child neurologists, geneticists, newborn screeners, neuroradiologists, transplanters and developmental pediatricians, was established in response to the advent of newborn screening for Krabbe Disease in New York State. As a result of the work of the New York State Krabbe consortium, the state’s newborn screening program has been widely accepted as the model for screening children with Krabbe and other Lysosomal Storage Disorders.

Members ensure that children identified through newborn screening receive the best possible immediate and long term follow-up and clinical care. Members meet regularly to discuss patient status, continuously expanding their knowledge about the long term outcomes of Krabbe Disease.

As additional states begin screening for Krabbe, their medical teams are included in the Consortium meetings. This collaboration is essential to ensure all children, in every state, are followed using the latest and best available standard of care.

For additional information on Krabbe Newborn Screening, please visit the Krabbe Newborn Screening section of our website.

Krabbe Mutation Database
The HJKRI and New York State’s Newborn Screening Wadsworth Laboratory are working together to analyze genotypes of Krabbe patients. Through newborn screening and the Krabbe World Wide Registry, these researchers are studying information gathered from patients’ specific genetic mutation causing Krabbe Disease, also known as genotype. This mutation analysis is then compared with known long term outcomes of the disease, which are contained in the WWR. Understanding the genotype/phenotype correlation will help physicians more accurately predict the onset and severity of the disease.

Psychosine
In collaboration with New York State’s Newborn Screening Wadsworth Laboratory, and the Mayo Clinic, researchers at the HJKRI are investigating the role of psychosine, a toxin that builds up in patients affected by Krabbe Disease. Through this study, researchers are working to determine if increased psychosine levels are associated with the onset of Krabbe Disease.

Preliminary results from Dieter Matern, MD, PhD and Joseph Orsini, PhD suggest that measuring psychosine in newborn dried blood spots could serve as a second tier test for Krabbe newborn screening.  Furthermore, this could also help determine disease progression in late onset Krabbe, as well as potential for disease progression following transplant.

Longitudinal Pediatric Data Resource
Created by the Newborn Screening Translational Research Network (NBSTRN), the Longitudinal Pediatric Data Resource (LPDR) allows physicians and researchers to collect, analyze and share patient information through a centralized database.

The HJKRI is taking steps to begin utilizing the LPDR, as it is the perfect format to house information contained in the WWR. Members from the Multi-State Krabbe Consortium will also be able to gather and store medical information from children who receive a positive screen for Krabbe Disease. The ability to follow children with Krabbe Disease using a centralized resource such as the LPDR, will greatly enhance the ability to correlate clinical outcomes with the genetic mutation causing the disease. Furthermore, this software provides the infrastructure to establish consistent long term follow up for children who receive a positive screen for Krabbe Disease.

For parents interested in learning more, we urge you to visit the ‘For Parents’ section of the NBSTRN website.

Using MRIs to Help Diagnose Different Forms of Krabbe Disease
A recent study conducted through the HJKRI shows promise for improving the predicition of symptom onset in Krabbe Disease. By looking at 64 MRI results from the WWR, research indicates that distinct differences appear on MRI scans among different types of Krabbe – early infantile, later onset and adolescent/adult.

Currently, New York State Consortium members and researchers at the HJKRI are sending MRI discs from Krabbe patients for review by Mount Sinai School of Medicine’s Thomas Naidich, MD, in an effort to correlate neuroradiological findings with onset, severity, and disease course.

For more about this study, please read the Foundation’s Press Release and the Full Abstract Article on the study.

Whole Genome Sequencing
HJKRI researchers in collaboration with James Lupski, MD, PhD from Baylor College of Medicine, are using whole genome sequencing to study the entire genetic code of Krabbe affected patients and family members. They are hoping to determine whether there is additional genetic information that can help predict disease outcome alongside GALC levels.

Lysosomal Disease Network
The Lysosomal Disease Network (LDN) is an NIH-funded consortium of numerous primary and affiliated medical research institutions, headquartered at the University of Minnesota, which cooperate in researching, developing, experimentally testing and implementing innovative diagnostic and treatment approaches for Lysosomal Storage Disorders.

The fact that the Lysosomal Disease Network consists of geographically-dispersed participating primary and affiliated institutions is the key to its effectiveness.  Since each of these diseases is rare in the general population, for any given disease, no single institution serves a large number of these patients. For any particular lysosomal disease research study, the participating Lysosomal Disease Network institutions conduct their research in close cooperation with one another, almost as if they were one single institution.  This approach maximizes the number of available research subjects for each researched disease, greatly increasing the scope and validity of the new knowledge gained through these multi-site research studies.

For more information please visit www.LysosomalDiseaseNetwork.org