Spotlight on Research - Dr. Escolar

Dr. Escolar is an Assistant Professor of Pediatrics and a Developmental and Behavioral Pediatrician at the Clinical Center for the Study of Development and Learning at the University of North Carolina at Chapel Hill. Her research program is titled "Development of a Staging System for Infantile Krabbe Disease."

The following are some highlights from a recent interview with Dr. Escolar about this research.

How do you see your work benefiting the future of children born with Krabbe, Leukodystrophies, and other inborn errors of metabolism?
As part of this program, we are researching the natural history of these diseases and how the treatments are affecting outcome in terms of brain development.

The two main goals are:

• To increase our understanding of how vulnerable the central nervous system is to metabolic insults at different stages of brain development
• To more clearly understand how treatments impact children's lives overall

Through the Hunter's Hope grant, all children referred with Krabbe Disease are seen in our program, those recently diagnosed, as well as those transplanted. To date, we have evaluated 26 children with Krabbe and are actively following 16 of these children.

Initially, a child receives a 4-hour evaluation. We work with the child and the child's timeline, adjusting our schedule to their eating and sleeping requirements. The evaluation is multi-disciplinary and involves a Neuropsychologist, Developmental Pediatrician, Physical Therapist, Occupational Therapist, Speech and Language Pathologist, Audiologist, Social Worker and Nurse. After each evaluation, all of these specialists meet to discuss, share and exchange information about what the child did.

We are working to improve the understanding of the correlation between clinical diagnostic tools like neuroimaging, nerve conduction studies, spinal fluid protein levels and neurodevelopmental function. We are seeing remylination post-transplant, and are trying to understand how that relates to functional improvements in the children. This is important to know for the future, because we must understand the effects of novel therapies. Our work now will help to provide clinicians with tools to assess how severe the disease is, how it has affected the child and the possibilities of treatment for the child. There are direct clinical and research components that must be put together, as if they were puzzle pieces.

This comprehensive assessment will help families prioritize and plan for the future needs of the children in terms of Quality of Life issues. Because of the Hunter's Hope grant, I have been able to set up a database and look at every child's data and analyze this information. Regarding early development, we help parents understand issues they will face in the future. The specialists sit with the families to explain evaluation results, prioritize needs, and recommend whom to contact for help. The social worker provides support to families to help them get the services that the child needs. We can help to guide them with whom they should talk to, and help them with appeals and letter writing.

In the next couple of years we will begin to see more newborn transplant children reach school age. Working with the children's schools is important if there are developmental issues. Additionally, we can help parents advocate for their children. Making sure the parents get the most accurate information for their child's skill level is paramount. We will continually work with parents if there are developmental issues that need attention to maximize each child's potential. Every child is different. But, there shouldn't be anything that prohibits these children from having a high quality of life, becoming independent, and as adults becoming productive citizens.

Why is it important to study the affected children, who are not eligible for transplant?
It will provide vital information to help understand the natural history of the disease. It will also help us determine if there are any correlations between genotype and phenotype.

How will the affected children's participation in this research program benefit the children born in the future with Krabbe Disease?
Their participation will greatly help to further research towards a better understanding of the impact of treatments in disease progression. It is vital that we understand how this works, so we can move forward. This will help us understand how we are making a difference with the children who have received the transplant. Right now we are doing a staging of Krabbe based on the children that have received a transplant. Even better would be to do a disease staging based on all the children born with Krabbe Disease. It would be helpful for children born in the future, if, when a child is diagnosed with Krabbe, they could be evaluated in this program at that time, as well as a year later and potentially another 6 months to a year after that.

Is there any way that parents of children who have passed away from Krabbe Disease can help to further this research?
Yes. Their children's medical records would yield a bounty of valuable information. Medical records that would be helpful include developmental evaluations, neurological evaluations, MRIs, NCS, enzyme levels and or spinal fluid protein tests. After signing consent to participate in the study, parents could mail copies of their children's medical records to me and I could include them in my database. This vital information will help to aid in the pace of development of a complete staging for Krabbe Disease. Additionally, any photos or videos would be helpful.

When and how will your work being published in medical journals help children with Krabbe and other leukodystrophies, both symptomatic and transplanted children? I am in the process of writing an article focusing on understanding the development in children with Krabbe that will be submitted to a peer-reviewed journal very soon. This information will help to educate pediatricians and aid them in obtaining a quicker diagnosis of Krabbe Disease. Pediatricians will think of the urgency of treatment and not wait until the next scheduled appointment. They will instead treat this child's illness like it is an emergency. As we know, every day counts when you are dealing with Krabbe. The pediatricians will see how important it is to act early to help these children.

Thank You, Dr. Maria Escolar.

Dr. Escolar's work is pioneering in the understanding of the natural history and the development of children born with Krabbe Disease. Through her program, children born with Krabbe now have the chance to help children born in the future. Her published work will be a huge step toward early diagnosis and the saving of lives of the future generation of Krabbe children. We are grateful for her and all the dedicated specialists that support the "Development of a Staging System for Infantile Krabbe Disease" Program. We are also grateful to all our supporters that made it possible for Hunter's Hope to provide funding for this important research. We thank you all.