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Shunt Alternative Research

Most hydrocephalus-related research has studied problems related to brain injury caused by hydrocephalus.
These problems include:
  • Increased brain pressure (intracranial pressure)
  • Stroke (cerebral ischemia)
  • Low levels of oxygen (hypoxia)
  • Physical disruption of axons and neurons
  • Changes in the extracellular microenvironment
Using two-dimensional electrophoresis, past studies identified fewer than 100 proteins in CSF. Using new high-resolution mass spectrometry (HRMS) techniques gives us the ability to identify thousands of CSF proteins. As far as we know, scientists have not used HRMS to study the proteins and genes in the ventricular CSF of children with hydrocephalus. We hope that our findings will lead to treatment for hydrocephalus that changes these proteins and genes instead of installing shunts.

Dr. Anthony M. Avellino

Hydrocephalus Research at Seattle Children’s Research Institute
Seattle Children’s Pediatric neurosurgeon Dr. Anthony Avellino is trying to think “outside of the box” with his approach to hydrocephalus research. He wants to understand the nature of cerebrospinal fluid and its composition to better understand hydrocephalus. He is committed to advance better treatment outcomes and hopefully find a cure.

Questions and answers with Dr. Anthony M. Avellino
Q: What is the focus of your research?
A: Our team is:
  • Studying and defining the proteins in the CSF of children with and without hydrocephalus
  • Defining the combinations of proteins (profiles) in children with and without hydrocephalus that may affect their cognitive development
  • Identifying and understanding the nature of thousands of proteins in complex CSF protein mixtures from children with and without hydrocephalus
  • Doing this with a speed, sensitivity and accuracy not possible before with other methods
  • Using this information to regulate proteins and genes in order to avoid using shunts

Q: How will these findings benefit children with hydrocephalus?
A: They will help us:
  • Better understand the development of hydrocephalus in relation to injury, survival and brain development
  • Develop new molecular and medicine therapies to balance the proteins in a child’s CSF that regulate CSF production and/or absorption
  • Increase the body’s ability to absorb CSF
  • Find ways to treat children without using ventricular shunts
  • Improve a child’s chance of normal neurological and cognitive development

Related Links

Dr. Anthony M. Avellino’s current research focuses on better understanding hydrocephalus and improving neurological and cognitive development in children with this condition.

This content is from Dr. Avellino's research, and has been provided by Seattle Children's & Regional Medical Center Neurosurgery website.

Proteomics Research
Eugene Kolker, PhD is the chief data officer and principal investigator of the Center for Developmental Therapeutics at the Seattle Children’s Research Institute. He has superb expertise in proteomics and is the Editor-in-Chief of the OMICS, A Journal of Integrative Biology.

Proteomics is the study and characterization of proteins, an exciting research area with great potential for treatment and screening of many health conditions. Molecular mechanisms behind hydrocephalus have not been investigated thoroughly, precluding understanding and the development of better treatments or finding its cure. Little to nothing is currently known about proteomics of hydrocephalus patients. There are many primary causes of hydrocephalus; each potentially produces a different proteomics profile and can be characterized by distinct biomarkers. Outcomes following shunt placement and other interventions vary highly and unpredictably: two very similar children with hydrocephalus may receive identical shunts; yet only one may escape developmental problems. We seek to understand the factors that influence these different outcomes.

Proteomics allows us to (1) identify protein biomarkers and distinct proteomics profiles, (2) correlate these biomarkers with different types and severity levels of hydrocephalus, and (3) develop predictive models for outcomes based on these biomarkers. Proteomics hinges upon access to specialized expertise, sophisticated modeling and cutting edge equipment. The Kolker Lab brings to this effort unique statistical and mass spectrometry capabilities and synergistic leverage with existing funded projects. A dedicated expert (a Fellow) paired with the appropriate resources would bolster hydrocephalus proteomics research. With these tools, we can extract the most information from each sample to identify trends for hydrocephalus diagnostics.

A donation of $1,000 purchases a Kit for Calibration Reagents and Analytical Columns– Mass spectrometry instrumentation requires monthly tuning with protein standards to keep it functioning within known parameters, increasing confidence and accuracy.

Giving $2,000 buys the time and reagents necessary to perform one sample run including expert sample preparation, bio-separation, and data analysis.

A donation of $3,000 provides a Depletion Column – Sophisticated depletion columns are used during preparation of samples to remove high-abundance (common) proteins and increase our overall ability to identify low-abundance (rare) proteins. Disease biomarkers are often those of lowest abundance.

Giving $5,000 dollars purchases a Nanosource Mass Spectrometry Source– A special device which increases the sensitivity of our mass spectrometer, allowing detection of rare proteins in minute quantities. This increases both sensitivity and accuracy of results.

Donating $10,000 buys automation equipment which when paired to our purification tools will lead to increased reliability of sample preparation and hence increased comprehensive protein analysis of disease severity.

Giving $50,000 provides specialized equipment for breaking samples into multiple portions, each with reduced complexity compared to the entire sample, allowing us to learn things about each sample which would otherwise be hidden.

A donation of $80,000 hires a fulltime Research Fellow to study hydrocephalus exclusively. Dedicated expertise will ensure a focal point for hydrocephalus research.

Giving $240,000 establishes 3-year fellowship for a fulltime Research Fellow dedicated exclusively to hydrocephalus research.

Donating $660,000 buys a cutting-edge LTQ-XL Orbitrap mass spectrometer that will allow ultra-sensitive identification of hydrocephalus-specific proteins.

These are necessary steps towards creating a critical mass of hydrocephalus proteomics research. With your help we can unite dedicated scientists with the resources needed to advance understanding of the mechanisms behind hydrocephalus in pursuit of a cure.

 
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